array:23 [
  "pii" => "S2173574321000538"
  "issn" => "21735743"
  "doi" => "10.1016/j.reumae.2019.10.004"
  "estado" => "S300"
  "fechaPublicacion" => "2021-04-01"
  "aid" => "1379"
  "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología"
  "copyrightAnyo" => "2019"
  "documento" => "simple-article"
  "crossmark" => 1
  "subdocumento" => "crp"
  "cita" => "Reumatol Clin. 2021;17:187-91"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:1 [
    "total" => 0
  ]
  "itemSiguiente" => array:18 [
    "pii" => "S2173574321000381"
    "issn" => "21735743"
    "doi" => "10.1016/j.reumae.2019.07.006"
    "estado" => "S300"
    "fechaPublicacion" => "2021-04-01"
    "aid" => "1355"
    "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "fla"
    "cita" => "Reumatol Clin. 2021;17:192-6"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>"
      "titulo" => "Comparison of disease activity in patients with ankylosing spondylitis under TNFi or NSAID treatment&#44; is there any difference&#63; An observational study"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "192"
          "paginaFinal" => "196"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Comparaci&#243;n de la actividad de la enfermedad en pacientes de espondilitis anquilosante con terapia de anti-TNF o AINE&#46; &#191;Existe alguna diferencia&#63; Estudio observacional"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0010"
          "etiqueta" => "Fig&#46; 2"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr2.jpeg"
              "Alto" => 945
              "Ancho" => 2082
              "Tamanyo" => 57015
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Clinical disease activity in patients with TNFi treatment compared with those with NSAID&#46; NSAID&#58; non-steroidal anti-inflammatory drugs&#59; TNFi&#58; TNF inhibitors&#59; low disease activity&#58; BASDAI<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>4&#59; inactive disease&#58; BASDAI<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>2&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Mireia Moreno, Marta Ar&#233;valo, Marc Zamora, Caridad Pontes, Juan Carlos Oliva, Jordi Gratac&#243;s"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "Mireia"
              "apellidos" => "Moreno"
            ]
            1 => array:2 [
              "nombre" => "Marta"
              "apellidos" => "Ar&#233;valo"
            ]
            2 => array:2 [
              "nombre" => "Marc"
              "apellidos" => "Zamora"
            ]
            3 => array:2 [
              "nombre" => "Caridad"
              "apellidos" => "Pontes"
            ]
            4 => array:2 [
              "nombre" => "Juan Carlos"
              "apellidos" => "Oliva"
            ]
            5 => array:2 [
              "nombre" => "Jordi"
              "apellidos" => "Gratac&#243;s"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574321000381?idApp=UINPBA00004M"
    "url" => "/21735743/0000001700000004/v1_202103261153/S2173574321000381/v1_202103261153/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S217357432100054X"
    "issn" => "21735743"
    "doi" => "10.1016/j.reumae.2019.09.004"
    "estado" => "S300"
    "fechaPublicacion" => "2021-04-01"
    "aid" => "1370"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and Sociedad Espa&#241;ola de Reumatolog&#237;a y Colegio Mexicano de Reumatolog&#237;a"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "fla"
    "cita" => "Reumatol Clin. 2021;17:183-6"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Special Article</span>"
      "titulo" => "Pregnancy control in patients with systemic lupus erythematosus&#47;antiphospholipid syndrome&#46; Part 3&#58; Childbirth&#46; Puerperium&#46; Breastfeeding contraception&#46; Newborn"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "183"
          "paginaFinal" => "186"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Control del embarazo en pacientes con lupus eritematoso sist&#233;mico&#47;s&#237;ndrome antifosfol&#237;pido&#46; Parte 3&#46; Parto&#46; Puerperio&#46; Lactancia&#46; Anticoncepci&#243;n&#46; Reci&#233;n nacido"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Paloma Delgado, &#193;ngel Robles, Juan Antonio Mart&#237;nez L&#243;pez, Luis S&#225;ez-Comet, Esther Rodr&#237;guez Almaraz, Nuria Mart&#237;nez-S&#225;nchez, Amaia Ugarte, Paloma Vela-Casasempere, Beatriz Marco, Gerard Espinosa, Maria Galindo, Manel Casellas, Guillermo Ruiz-Irastorza, Victor Mart&#237;nez-Taboada, Jose Luis Bartha"
          "autores" => array:15 [
            0 => array:2 [
              "nombre" => "Paloma"
              "apellidos" => "Delgado"
            ]
            1 => array:2 [
              "nombre" => "&#193;ngel"
              "apellidos" => "Robles"
            ]
            2 => array:2 [
              "nombre" => "Juan Antonio"
              "apellidos" => "Mart&#237;nez L&#243;pez"
            ]
            3 => array:2 [
              "nombre" => "Luis"
              "apellidos" => "S&#225;ez-Comet"
            ]
            4 => array:2 [
              "nombre" => "Esther"
              "apellidos" => "Rodr&#237;guez Almaraz"
            ]
            5 => array:2 [
              "nombre" => "Nuria"
              "apellidos" => "Mart&#237;nez-S&#225;nchez"
            ]
            6 => array:2 [
              "nombre" => "Amaia"
              "apellidos" => "Ugarte"
            ]
            7 => array:2 [
              "nombre" => "Paloma"
              "apellidos" => "Vela-Casasempere"
            ]
            8 => array:2 [
              "nombre" => "Beatriz"
              "apellidos" => "Marco"
            ]
            9 => array:2 [
              "nombre" => "Gerard"
              "apellidos" => "Espinosa"
            ]
            10 => array:2 [
              "nombre" => "Maria"
              "apellidos" => "Galindo"
            ]
            11 => array:2 [
              "nombre" => "Manel"
              "apellidos" => "Casellas"
            ]
            12 => array:2 [
              "nombre" => "Guillermo"
              "apellidos" => "Ruiz-Irastorza"
            ]
            13 => array:2 [
              "nombre" => "Victor"
              "apellidos" => "Mart&#237;nez-Taboada"
            ]
            14 => array:2 [
              "nombre" => "Jose Luis"
              "apellidos" => "Bartha"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S1699258X19301329"
        "doi" => "10.1016/j.reuma.2019.09.004"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X19301329?idApp=UINPBA00004M"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S217357432100054X?idApp=UINPBA00004M"
    "url" => "/21735743/0000001700000004/v1_202103261153/S217357432100054X/v1_202103261153/en/main.assets"
  ]
  "en" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Brief Report</span>"
    "titulo" => "Role of Inflammasome Activation in Systemic Lupus Erythematosus&#58; Are Innate Immune Cells Activated&#63;"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "187"
        "paginaFinal" => "191"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Rodolfo Perez-Alamino, Raquel Cuchacovich, Luis R&#46; Espinoza, Constance P&#46; Porretta, Arnold H&#46; Zea"
        "autores" => array:5 [
          0 => array:4 [
            "nombre" => "Rodolfo"
            "apellidos" => "Perez-Alamino"
            "email" => array:1 [
              0 => "ofo_pa@hotmail.com"
            ]
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Raquel"
            "apellidos" => "Cuchacovich"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Luis R&#46;"
            "apellidos" => "Espinoza"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Constance P&#46;"
            "apellidos" => "Porretta"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Arnold H&#46;"
            "apellidos" => "Zea"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:4 [
          0 => array:3 [
            "entidad" => "Section of Rheumatology&#44; Department of Internal Medicine&#44; LSU Health Sciences Center&#44; 1542 Tulane Avenue&#44; New Orleans&#44; LA 70112&#44; USA"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Section of Rheumatology&#44; Hospital de Cl&#237;nicas Nicol&#225;s Avellaneda&#44; Tucum&#225;n&#44; Argentina&#44; 2000 Catamarca Street&#44; Tucum&#225;n&#44; PC 4000&#44; Argentina"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "School of Medicine&#44; Comprehensive Alcohol Research Center&#44; 533 Bolivar Street&#44; CSRB304&#44; New Orleans&#44; LA 70112&#44; USA"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Stanley S&#46; Scott Cancer Center&#44; Microbiology&#44; Immunology and Parasitology&#44; LSU Health Sciences Center&#44; 533 Bolivar Street&#44; CSRB 305&#44; New Orleans&#44; LA 70112&#44; USA"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Rol de la activaci&#243;n del inflammasome en lupus eritematoso sist&#233;mico&#58; est&#225;n las c&#233;lulas del sistema inmune innato activados&#63;"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2016
            "Ancho" => 2519
            "Tamanyo" => 277628
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Percentage of CD14<span class="elsevierStyleSup">&#43;</span>&#47;Caspase-1<span class="elsevierStyleSup">&#43;</span> expressing-cells&#46; A&#46; Cells were gated using FS vs SS to determine the &#37; of CD14<span class="elsevierStyleSup">&#43;</span>&#47;Caspase-1<span class="elsevierStyleSup">&#43;</span> cells in PBMC and Mono&#46; For lymphocytes it is only Caspase-1<span class="elsevierStyleSup">&#43;</span>&#46; Data from 14 SLE patients and 13 normal controls are presented&#44; as the mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#46; B&#46; Representative data from 1 normal control and 1 SLE patient dot plot showing the expression of CD14<span class="elsevierStyleSup">&#43;</span> vs&#46; Caspase-1<span class="elsevierStyleSup">&#43;</span> in PBMC &#40;1&#41;&#44; Lymph &#40;2&#41; and Mono &#40;3&#41;&#46; Stained cells were gated based on FSC and SSC parameters &#40;capase-1<span class="elsevierStyleSup">&#43;</span> lymphocytes in Q1 and PMBC and monocytes in Q2&#41;&#46; PBMC&#58; peripheral blood mononuclear cells&#59; Lym&#58; lymphocytes&#59; Mono&#58; monocytes&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Systemic lupus erythematosus &#40;SLE&#41; is a prototype of autoimmune disease&#44; characterized by a wide spectrum of clinical and immunologic abnormalities&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Exciting data have emerged over the last few years&#44; regarding the role of the inflammasome as an important component of the innate immune system&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2&#8211;4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The inflammasome is a large molecular platform constituted by a group of cytoplasmic protein complexes that senses a diverse set of inflammation-inducing stimuli&#44; including pathogen-associated molecular patterns &#40;PAMPs&#41;&#44; predominantly found in microbes and damage-associated molecular patterns &#40;DAMPs&#41; that are released as a result of perturbations of tissue homeostasis caused by microbial or non-microbial insults&#46; The central components of the inflammasome include&#58; &#40;1&#41; scaffold of the NOD-like receptors &#40;NLR&#41; family&#58; NLRP1&#44; NLRP3&#44; NLRC4 and AIM2&#59; &#40;2&#41; apoptosis associated speck-like protein containing a CARD &#40;ASC&#41;&#59; and &#40;3&#41; pro-Caspase-1&#46; The activated sensor can then recruit the other components of the inflammasome&#44; leading to the formation of the multiprotein complex containing pro-Caspase-1&#46; The assembly of these components leads to the autoproteolytic activation of Caspase-1&#44; which converts an immature IL-1&#946; and IL-18 to a mature secreted form&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">5&#8211;7</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Because the precise etiology and mechanisms leading to aberrant immune responses in SLE are not yet clearly understood&#44; we hypothesized that&#58; &#8220;inflammasome activation occurs in monocytes&#44; as a key element on the initiation and amplification of the innate immune response in SLE pathogenesis&#8221;&#46; Therefore&#44; the aims of this study were&#58; &#40;1&#41; To determine whether inflammasome activation occurs in monocytes of SLE patients&#59; and &#40;2&#41; to determine the relationship between the production of inflammasome related-cytokines and disease activity in these patients&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Patients selection</span><p id="par0025" class="elsevierStylePara elsevierViewall">Consecutive patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41; who fulfilled the revised ACR criteria for SLE were enrolled at Louisiana State University &#40;LSU&#41; outpatient Rheumatology clinics&#46; Consecutive patients without any inflammatory rheumatic disease were included as healthy controls &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#41;&#44; matched by age&#44; sex and ethnicity&#46; Patients with acute and&#47;or chronic infections&#44; including history of positive serology to HIV&#44; HBV and HCV were excluded&#46; All participants signed an informed consent form prior to their inclusion&#44; which was approved by LSU Institutional Review Board&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Demographic&#44; laboratory&#44; and clinical data were recorded&#46; Lupus disease activity was assessed by SELENA-SLEDAI score&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> A score &#8805;4 was defined as active disease&#46; Lupus nephritis &#40;LN&#41; &#40;absent&#44; past&#44; current&#41; was also recorded&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Collection and processing of blood samples</span><p id="par0035" class="elsevierStylePara elsevierViewall">Peripheral blood mononuclear cells &#40;PBMCs&#41; from patients and controls were isolated by Ficoll density gradient centrifugation &#40;Sigma Chemicals Co&#46;&#44; St Louis&#44; MO&#44; USA&#41;&#46; CD14<span class="elsevierStyleSup">&#43;</span> monocytes were purified from PBMCs&#44; using an autoMACS Separator and an autoMACS CD14<span class="elsevierStyleSup">&#43;</span> negative selection kit &#40;Miltenyi Biotec&#44; Germany&#41;&#46; Purified monocytes were cultured in six well plates &#40;1<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">6</span><span class="elsevierStyleHsp" style=""></span>monocytes&#47;well&#41; in RPMI 1640&#44; supplemented with 10&#37; fetal bovine serum&#44; 10<span class="elsevierStyleHsp" style=""></span>mM HEPES and 2<span class="elsevierStyleHsp" style=""></span>mM <span class="elsevierStyleSmallCaps">l</span>-Glutamine&#46; After cell adherence&#44; monocytes were stimulated &#40;&#8764;18<span class="elsevierStyleHsp" style=""></span>h&#41; with lipopolysaccharide &#40;LPS&#41; &#40;100<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41; in presence or absence of Caspase-1 inhibitor &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;M&#41; &#40;Caspase-1 inhibitor I&#44; cell-permeable&#44; YVAD-CHO&#41; &#40;Calbiochem&#44; Germany&#41;&#46; The remaining supernatants were stored at &#8722;70<span class="elsevierStyleHsp" style=""></span>&#176;C until assayed&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Intracellular Caspase-1 detection</span><p id="par0040" class="elsevierStylePara elsevierViewall">Fresh PBMCs were fixed-permeabilized&#44; and stained with CD14<span class="elsevierStyleSup">&#43;</span> &#40;FITC&#41; &#40;Beckman Coulter&#44; USA&#41; and Caspase-1 &#40;A-19&#41; &#40;PE&#41; antibodies &#40;Santa Cruz Biotechnology&#44; USA&#41;&#46; Caspase-1 expression was measured by flow cytometry on a BD FACSCantor II flow cytometer &#40;Becton Dickinson&#44; San Jose&#44; CA&#41;&#46; Log fluorescence of the gated population was measured and 20&#44;000 cells were acquired for each sample&#46; Caspase-1 expression corresponded to the average of 2 determinations made for each patient and control&#46; Data analysis was performed using BD FACSDiva software version 6&#46;1&#46;3&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Cytokine measurement</span><p id="par0045" class="elsevierStylePara elsevierViewall">IL-1&#946; and IL-18 levels were determined in patients plasma and cell culture supernatants by human Quantikine ELISA kits &#40;R&#38;D Systems&#44; USA&#41;&#44; following the manufacturer&#39;s instructions&#46; Since the assay range for IL-1&#946; is between 3&#46;9 and 250<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#44; we extended down the lower range of the standards 3 dilutions giving us a range between 0&#46;100&#8211;250<span class="elsevierStyleHsp" style=""></span>pg&#47;ml to maximize the presence of low values in our samples&#46; These extra dilutions did not alter the linearity of the standard curve&#46; Plasmatic cytokine levels of IL-1beta and IL-18 corresponded to the average of 2 determinations made for each patient and control&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0050" class="elsevierStylePara elsevierViewall">Descriptive values of variables were expressed as the mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#46; Variables with normal distribution were analyzed by Student&#39;s <span class="elsevierStyleItalic">t</span>-test and those with non-normal distribution were analyzed with Mann&#8211;Whitney test&#46; <span class="elsevierStyleItalic">p</span>-Values less than 0&#46;05 were considered significant&#46; The statistical analysis was carried out using GraphPad Prism software &#40;version 5&#46;0&#41;&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall">Fourteen &#40;14&#41; consecutive SLE patients were included in the study&#46; Thirteen out of 14 patients &#40;93&#37;&#41; were female and 8&#47;14 &#40;57&#37;&#41; were African-Americans&#46; The mean age of the patients at the time of the study was 32&#46;7 &#40;&#177;9&#46;1&#41; years&#44; and the mean disease duration was 8&#46;9 years &#40;&#177;6&#46;4&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#44; the percentage of CD14<span class="elsevierStyleSup">&#43;</span> vs&#46; Caspase-1<span class="elsevierStyleSup">&#43;</span> expression was found to be significantly higher in fresh PBMCs and in the monocytic population from SLE patients compared to normal controls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#44; respectively&#41;&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B shows the percentage of Caspase-1 positive cells in PBMCs and monocytes &#40;<span class="elsevierStyleItalic"><span class="elsevierStyleBold">quadrant 2</span></span>&#41; from one control and one SLE-patient&#46; The majority of Caspase-1 positive cells were observed in the monocytic population from patients with SLE &#40;68&#46;4&#37;&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Interestingly&#44; the increased numbers of Caspase-1 positive cells directly paralleled with significantly higher plasma levels of IL-1&#946; &#40;2&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;05<span class="elsevierStyleHsp" style=""></span>pg&#47;ml vs&#46; 1&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;10<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;008&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41; and IL-18 &#40;725&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>215&#46;4<span class="elsevierStyleHsp" style=""></span>pg&#47;ml vs&#46; 479&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>125&#46;2<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; in SLE patients when compared to normal controls &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#46; Furthermore&#44; we observed that levels of IL-18 were significantly higher &#40;834&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>179&#46;3<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; in patients presenting high disease activity &#40;SELENA-SLEDAI &#8805;6&#41;&#44; compared to patients with mild disease or remission &#40;572&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>171&#46;6<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; No statistical differences in levels of IL-1&#946; were observed between SLE patients with high vs&#46; mild disease activity &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>A and B&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Compared to normal controls&#44; purified monocytes from SLE patients displayed a robust inflammatory response when cultured in vitro&#46; As shown in <a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>A&#44; when monocytes from normal controls and SLE patients were stimulated with LPS&#44; there was a 60 &#40;mean&#58; 4597<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3515<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; and 100 &#40;mean&#58; 8895<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3475<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; fold increase in IL-1&#946; compared to non-stimulated monocytes &#40;mean&#58; 88&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;8&#41;&#46; No significant differences in IL1-&#946; production were observed between LPS-stimulated monocytes from controls and SLE patients&#46; Similar production pattern of IL-18 was observed &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>B&#41;&#44; where the mean of IL-18 production was significantly higher &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; in supernatants from stimulated monocytes from SLE-patients &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; than in non-stimulated&#46; Furthermore&#44; IL-18 production in LPS-stimulated monocytes from SLE patients was 3 fold higher when compared to normal controls &#40;mean&#58; 103&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>213&#46;2<span class="elsevierStyleHsp" style=""></span>pg&#47;ml and 30&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#46;9<span class="elsevierStyleHsp" style=""></span>pg&#47;ml respectively&#41;&#46; In <a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>A&#44; there was a slight reduction in IL-1&#946; production in LPS-stimulated normal monocytes plus the inhibitor&#44; that was not observed in SLE patients&#46; In contrast&#44; as seen in <a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>B&#44; a reduction of approximately 3 fold in IL-18 production was observed in supernatants of LPS-stimulated monocytes from SLE patients plus inhibitor&#46; Significant correlations between Caspase-1 expression&#47;cytokine production and clinical manifestations&#44; treatment or serologic markers of the disease were not found in this study&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">The major finding of this pilot study is that in vitro&#44; monocytes from SLE patients showed an increased expression of Caspase-1 that parallels with significant higher levels of inflammasome-related cytokines&#44; IL-1&#946; and IL-18&#44; in patients with SLE as compared to healthy subjects&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">How the inflammasome is triggered and activated in SLE&#44; has become an important concept to understand its role in this disease&#46; Immune complexes formed secondary to antibody recognition of DNA or RNA antigens&#44; have been shown to stimulate inflammasome activation through up-regulation of TLR-dependent activation of NF&#954;&#946; and subsequent activation of the NLRP3 inflammasome&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">9&#44;10</span></a> C3a&#44; which is released during complement activation in tissues&#44; promotes inflammasome activation through up-regulation of ATP secretion&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> Neutrophil extracellular traps &#40;NETs&#41; have also been proposed to play a pathogenic role in SLE&#46; Recently&#44; NETs have been shown to activate caspase-1&#44; resulting in release of IL-1&#946; and IL-18&#44; and this activation was enhanced in macrophages derived from SLE patients&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Because innate immune cells are crucial for the onset of the immune response&#44; inflammasome activation in these cells may promote the initiation and amplification of the autoimmune response&#46; In this study&#44; we found an increased expression of Caspase-1 in monocytes from SLE patients&#44; as compared with healthy controls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#46; To our knowledge this is the first study in demonstrating that basal inflammasome activation occurs in fresh isolated monocytes from SLE patients&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">IL-1&#946; and IL-18 cytokines&#44; hallmarks of inflammasome activation&#44; belong to the IL-1 cytokine family&#46; IL-1&#946; is critical to the pathology of most autoinflammatory and many autoimmune diseases&#46; IL-18 was discovered initially as an IFN-&#947; inducing factor&#44; and since then has been known as a prototypical Th-1 cytokine&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> In our study&#44; plasma levels of these cytokines were found to be significantly higher in SLE patients as compared to normal controls&#46; Recently&#44; Liu et al&#46; have also shown an enhanced inflammasome activity in SLE patients&#44; mediated by type I IFN&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">In this study&#44; we focused on investigating the capacity of monocytes from SLE patients to secrete inflammasome-related cytokines at the basal level&#44; and in response to the inflammatory stimuli LPS&#44; as compared with monocytes from healthy individuals&#46; As expected&#44; monocytes from SLE patients displayed a robust inflammatory response after LPS stimulation&#44; characterized by elevated levels of IL-1&#946; and IL-18 when compared to stimulated monocytes from healthy individuals&#46; In addition&#44; the production of IL-18 was reduced by almost 3 fold when Caspase-1 inhibitor was added to the cultures&#46; There was also a reduction in levels of IL-1&#946; in supernatants treated with Caspase-1 inhibitor&#44; although in less extent compared to IL-18&#46; A possible explanation might be related by the extraordinary high amount of IL-1&#946; released&#44; as compared to IL-18&#46; The inhibitor is competitive&#44; so inhibition could be overcome by substrate excess&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">A growing body of evidence supports the pivotal role of infections in the induction or exacerbation of SLE&#46; Infections can be responsible for aberrant immune response leading to a loss of tolerance toward native proteins&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a> Our findings suggest that monocytes from SLE patients might have an abnormal expression of IL-18 and IL-1&#946;-regulating molecules in response to infection&#44; thus resulting in anomalous activation of adaptive immune responses&#44; which can be the basis by which SLE develops and flares&#46; On the other hand&#44; we also agree that the main limitation of the study is the small number of the sample&#46; However&#44; despite this&#44; we were able to demonstrate the activation of the inflammasome in monocytes of SLE patients&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">In conclusion&#44; our study shows that monocytes from SLE patients exhibit an enhanced activation of the inflammasome complex in vitro&#44; which is the product of elevated expression of Caspase-1 and inflammasome-related cytokines&#46; The results of this proof of concept study indicate a potential role of the inflammasome pathway in the pathogenesis of SLE&#44; thus identifying a novel pathway for therapeutic targeting&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Ethical approval</span><p id="par0110" class="elsevierStylePara elsevierViewall">All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and&#47;or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Informed consent</span><p id="par0115" class="elsevierStylePara elsevierViewall">Informed consent was obtained from all individual participants included in the study&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflict of interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest to disclose&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:13 [
        0 => array:3 [
          "identificador" => "xres1489849"
          "titulo" => "Abstract"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Background"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "Methods"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "Results"
            ]
            3 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Conclusions"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1352808"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres1489850"
          "titulo" => "Resumen"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Introducci&#243;n"
            ]
            1 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "Objetivos"
            ]
            2 => array:2 [
              "identificador" => "abst0035"
              "titulo" => "Materiales y m&#233;todos"
            ]
            3 => array:2 [
              "identificador" => "abst0040"
              "titulo" => "Resultados"
            ]
            4 => array:2 [
              "identificador" => "abst0045"
              "titulo" => "Conclusiones"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec1352809"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Materials and methods"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Patients selection"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Collection and processing of blood samples"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Intracellular Caspase-1 detection"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Cytokine measurement"
            ]
            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Statistical analysis"
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Results"
        ]
        7 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Ethical approval"
        ]
        9 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Informed consent"
        ]
        10 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Conflict of interest"
        ]
        11 => array:2 [
          "identificador" => "xack521618"
          "titulo" => "Acknowledgements"
        ]
        12 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2019-05-30"
    "fechaAceptado" => "2019-10-17"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1352808"
          "palabras" => array:6 [
            0 => "Systemic lupus erythematosus"
            1 => "Pathogenesis"
            2 => "Inflammasomes"
            3 => "Innate immunity"
            4 => "Caspase-1"
            5 => "Cytokines"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1352809"
          "palabras" => array:6 [
            0 => "Lupus eritematoso sist&#233;mico"
            1 => "Patog&#233;nesis"
            2 => "Inflamasoma"
            3 => "Inmunidad innata"
            4 => "Caspasa-1"
            5 => "Citoquinas"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Systemic lupus erythematosus &#40;SLE&#41; is characterized by a wide spectrum of clinical and immunological abnormalities&#46; New data have emerged about the role of inflammasomes in autoimmune diseases&#46; We aimed to investigate whether basal inflammasome activation occurs in SLE patients&#44; and whether a relationship between inflammasome-related-cytokines and disease activity exists&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Fourteen &#40;14&#41; consecutive SLE patients and 13 healthy individuals&#44; matched by sex&#44; age and ethnicity&#44; were included&#46; Demographics&#44; laboratory and clinical data were recorded&#46; Peripheral blood mononuclear cells &#40;PBMCs&#41; from patients and controls were obtained and monocytes were isolated by negative selection&#46; Purified monocytes were stimulated with LPS in the presence or absence of Caspase-1 inhibitor&#46; CD14 and Caspase-1 expression were analyzed by flow cytometry&#46; Cytokine levels were determined in plasma and culture supernatants by ELISA&#46; Student&#39;s <span class="elsevierStyleItalic">t</span> test and Mann&#8211;Whitney tests were used for statistical analysis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The percentage of CD14<span class="elsevierStyleSup">&#43;</span>&#47;Caspase-1<span class="elsevierStyleSup">&#43;</span> was significantly higher in monocytes from SLE patients compared to normal controls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46; These findings paralleled with higher plasma levels of IL-1&#946; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; and IL-18 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; in those patients&#46; Purified monocytes from SLE patients displayed a robust inflammatory response after LPS stimulation where Caspase-1&#44; IL-1&#946; and IL-18 were highly expressed&#46; Plasma levels of IL-18 were also significantly higher in SLE patients with active disease &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; In addition&#44; the production of IL-18 was reduced by 3 fold when Caspase-1 inhibitor was added to the cultures&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Monocytes from SLE patients exhibited increased inflammasome activation&#44; characterized by high expression of Caspase-1&#44; IL-1&#946; and IL-18&#46; Caspase-1 specific inhibitor decreased inflammasome activation &#40;in vitro&#41; by suppressing the production of IL-18&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El lupus eritematoso sist&#233;mico &#40;LES&#41; se caracteriza por presentar diversas anormalidades cl&#237;nicas e inmunol&#243;gicas&#46; El ensamblaje de los componentes del inflamasoma da lugar a la activaci&#243;n de caspasa-1&#44; generando la liberaci&#243;n de citoquinas pro-inflamatorias IL-1&#946; e IL-18&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Objetivos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Evaluar si existe una activaci&#243;n basal del inflamasoma en pacientes con LES y determinar la asociaci&#243;n de las citoquinas IL-1&#946; e IL-18 con la actividad de la enfermedad&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Materiales y m&#233;todos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 14 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41; pacientes consecutivos con LES y 13 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#41; controles&#44; pareados por edad&#44; sexo y raza&#46; Se recogieron datos cl&#237;nicos&#44; demogr&#225;ficos y de laboratorio&#46; Los monocitos fueron aislados a partir de c&#233;lulas mononucleares de sangre perif&#233;rica obtenidas de pacientes y controles&#46; Los monocitos purificados fueron estimulados con LPS&#44; en presencia y ausencia de inhibidor de caspasa-1&#46; La expresi&#243;n de CD14 y caspasa-1 fueron determinados por citometr&#237;a de flujo&#46; Niveles de citoquinas fueron determinadas en plasma y en sobrenadantes de cultivos mediante t&#233;cnica de ELISA&#46; Test de Student y Mann-Whitney fueron usados para el an&#225;lisis estad&#237;stico&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El porcentaje de CD14<span class="elsevierStyleSup">&#43;</span>&#47;caspasa-1<span class="elsevierStyleSup">&#43;</span> fue significativamente superior en monocitos de pacientes con LES vs&#46; controles &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#46; En forma paralela&#44; se encontraron niveles plasm&#225;ticos significativamente superiores de IL-1&#946; &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41; y de IL-18 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41; en pacientes con LES&#46; Monocitos purificados de pacientes l&#250;picos presentaron una robusta respuesta inflamatoria luego de ser estimulados con LPS&#44; donde caspasa-1&#44; IL-1&#946; e IL-18 fueron altamente expresados&#46; Niveles plasm&#225;ticos de IL-18 fueron significativamente mayores en pacientes con LES y enfermedad activa &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46; Por otro lado&#44; la producci&#243;n de IL-18 se redujo casi 3 veces cuando se agreg&#243; inhibidor de caspasa-1 en cultivos&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusiones</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Monocitos de pacientes con LES presentaron evidencia de activaci&#243;n de componentes del inflamasoma&#44; caracterizada por una mayor expresi&#243;n de caspasa-1&#44; IL-1&#946; e IL-18&#46; El inhibidor espec&#237;fico de caspasa-1 disminuy&#243; la activaci&#243;n del inflamasoma <span class="elsevierStyleItalic">in vitro&#44;</span> reduciendo la producci&#243;n de IL-18&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introducci&#243;n"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Objetivos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Materiales y m&#233;todos"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Resultados"
          ]
          4 => array:2 [
            "identificador" => "abst0045"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "multimedia" => array:4 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2016
            "Ancho" => 2519
            "Tamanyo" => 277628
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Percentage of CD14<span class="elsevierStyleSup">&#43;</span>&#47;Caspase-1<span class="elsevierStyleSup">&#43;</span> expressing-cells&#46; A&#46; Cells were gated using FS vs SS to determine the &#37; of CD14<span class="elsevierStyleSup">&#43;</span>&#47;Caspase-1<span class="elsevierStyleSup">&#43;</span> cells in PBMC and Mono&#46; For lymphocytes it is only Caspase-1<span class="elsevierStyleSup">&#43;</span>&#46; Data from 14 SLE patients and 13 normal controls are presented&#44; as the mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#46; B&#46; Representative data from 1 normal control and 1 SLE patient dot plot showing the expression of CD14<span class="elsevierStyleSup">&#43;</span> vs&#46; Caspase-1<span class="elsevierStyleSup">&#43;</span> in PBMC &#40;1&#41;&#44; Lymph &#40;2&#41; and Mono &#40;3&#41;&#46; Stained cells were gated based on FSC and SSC parameters &#40;capase-1<span class="elsevierStyleSup">&#43;</span> lymphocytes in Q1 and PMBC and monocytes in Q2&#41;&#46; PBMC&#58; peripheral blood mononuclear cells&#59; Lym&#58; lymphocytes&#59; Mono&#58; monocytes&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 2082
            "Ancho" => 1447
            "Tamanyo" => 266251
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Plasma levels of inflammasome-related cytokines&#46; A and B&#46; IL-1&#946; and IL-18 level in the plasma of &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#41; normal controls and &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41; SLE patients were determined by ELISA&#46; IL1&#946; and IL-18 were significantly high expressed in SLE patients compared to normal controls&#46; Data are presented as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD from duplicates&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 2342
            "Ancho" => 1578
            "Tamanyo" => 311622
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Plasma levels of inflammasome-related cytokines and disease activity&#46; A and B&#46; Plasmatic levels of IL-1&#946; and IL-18 were tested by ELISA in &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41; SLE patients in remission and &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41; SLE patients with active disease &#40;SLEDAI<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>4&#41;&#46; Data are presented as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD from duplicates&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Fig&#46; 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 2382
            "Ancho" => 1457
            "Tamanyo" => 192314
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">LPS induces secretion of high levels of IL-1&#946; and IL-18 in monocytes from SLE patients&#46; Purified CD14<span class="elsevierStyleSup">&#43;</span> monocytes were incubated with LPS &#40;100<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41;&#44; in the presence or absence of Caspase-1 inhibitor &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;M&#41;&#46; IL-1&#946; &#40;A&#41; and IL-18 &#40;B&#41; concentrations were measured in supernatants by specific ELISA after &#8764;18-h incubation&#46; Data is representative as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD from duplicates&#46; NS&#58; Non-stimulated&#59; LPS&#58; lipopolysaccharide&#59; Inh&#58; Caspase-1 inhibitor&#59; SLE&#58; systemic lupus erythematosus&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:15 [
            0 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The pathogenesis of systemic lupus erythematosus-an up-date"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46; Choi"
                            1 => "S&#46; Taek Kim"
                            2 => "J&#46; Craft"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.coi.2012.10.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Opin Immunol"
                        "fecha" => "2012"
                        "volumen" => "24"
                        "paginaInicial" => "651"
                        "paginaFinal" => "657"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23131610"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inflammasomes and rheumatic diseases&#58; evolving concepts"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "P&#46; Sidiropoulos"
                            1 => "G&#46; Goulielmos"
                            2 => "G&#46; Voloudakis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2007.078014"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2008"
                        "volumen" => "67"
                        "paginaInicial" => "1382"
                        "paginaFinal" => "1389"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17921182"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inflammasomes and autoimmunity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "P&#46; Shaw"
                            1 => "M&#46;F&#46; McDermott"
                            2 => "T&#46;D&#46; Kanneganti"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.molmed.2010.11.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Trends Mol Med"
                        "fecha" => "2010"
                        "volumen" => "17"
                        "paginaInicial" => "57"
                        "paginaFinal" => "64"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21163704"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inflammatory Caspase-1s&#58; linking an intracellular innate immune system to autoinflammatory diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "F&#46; Martinon"
                            1 => "J&#46; Tschopp"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cell.2004.05.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell"
                        "fecha" => "2004"
                        "volumen" => "117"
                        "paginaInicial" => "561"
                        "paginaFinal" => "574"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15163405"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inflammasomes in health and disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "T&#46; Strowig"
                            1 => "J&#46; Henao-Mejia"
                            2 => "E&#46; Elinav"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nature10759"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nature"
                        "fecha" => "2012"
                        "volumen" => "481"
                        "paginaInicial" => "278"
                        "paginaFinal" => "286"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22258606"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The inflammasomes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "K&#46; Schroder"
                            1 => "J&#46; Tschopp"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cell.2010.01.040"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell"
                        "fecha" => "2010"
                        "volumen" => "140"
                        "paginaInicial" => "821"
                        "paginaFinal" => "832"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20303873"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The role of inflammasome-derived IL-1 in driving IL-17 responses"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "K&#46; Mills"
                            1 => "L&#46; Dungan"
                            2 => "S&#46; Jones"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1189/jlb.0812424"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Leukoc Biol"
                        "fecha" => "2013"
                        "volumen" => "93"
                        "paginaInicial" => "1"
                        "paginaFinal" => "9"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23284088"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Derivation of the SLEDAI&#46; A disease activity index for lupus patients&#46; The Committee on Prognosis Studies in SLE"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "C&#46; Bombardier"
                            1 => "D&#46;D&#46; Gladman"
                            2 => "M&#46;B&#46; Urowitz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.1780350606"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "1992"
                        "volumen" => "35"
                        "paginaInicial" => "630"
                        "paginaFinal" => "640"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1599520"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46; Baroja-Mazo"
                            1 => "F&#46; Martin-Sanchez"
                            2 => "A&#46;I&#46; Gomez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ni.2919"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Immunol"
                        "fecha" => "2014"
                        "volumen" => "15"
                        "paginaInicial" => "738"
                        "paginaFinal" => "748"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24952504"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Self Double-Stranded &#40;ds&#41; DNA induces IL-1&#946; production from human monocytes by activating NLRP3 inflammasome in the presence of anti-dsDNA antibodies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "M&#46;S&#46; Shin"
                            1 => "Y&#46; Kang"
                            2 => "N&#46; Lee"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "2013"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8759771"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "C3a modulates IL-1&#946; secretion in human monocytes by regulating ATP efflux and subsequent NLRP3 inflammasome activation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "E&#46; Asgari"
                            1 => "G&#46; Le Friec"
                            2 => "H&#46; Yamamoto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2013-05-502229"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2013"
                        "volumen" => "122"
                        "paginaInicial" => "3473"
                        "paginaFinal" => "3481"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23878142"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neutrophil extracellular trap-associated protein activation of the NLRP3 inflammasome is enhanced in lupus macrophages"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46;M&#46; Kahlenberg"
                            1 => "C&#46; Carmona-Rivera"
                            2 => "C&#46;K&#46; Smith"
                            3 => "M&#46;J&#46; Kaplan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4049/jimmunol.1202388"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "2013"
                        "volumen" => "190"
                        "paginaInicial" => "1217"
                        "paginaFinal" => "1226"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23267025"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The IL-1 family&#58; regulators of immunity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;E&#46; Sims"
                            1 => "D&#46;E&#46; Smith"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nri2691"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Immunol"
                        "fecha" => "2010"
                        "volumen" => "10"
                        "paginaInicial" => "89"
                        "paginaFinal" => "102"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20081871"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Enhanced inflammasome activity in systemic lupus erythematosus is mediated via type I interferon-induced up-regulation of interferon regulatory factor 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46; Liu"
                            1 => "C&#46;C&#46; Berthier"
                            2 => "J&#46;M&#46; Kahlenberg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.40166"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheumatol"
                        "fecha" => "2017"
                        "volumen" => "69"
                        "paginaInicial" => "1840"
                        "paginaFinal" => "1849"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28564495"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Infections as triggers and complications of systemic lupus erythematosus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46; Doria"
                            1 => "M&#46; Canova"
                            2 => "M&#46; Tonon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.autrev.2008.07.019"
                      "Revista" => array:6 [
                        "tituloSerie" => "Autoimmun Rev"
                        "fecha" => "2008"
                        "volumen" => "8"
                        "paginaInicial" => "24"
                        "paginaFinal" => "28"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18703174"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
    "agradecimientos" => array:1 [
      0 => array:4 [
        "identificador" => "xack521618"
        "titulo" => "Acknowledgements"
        "texto" => "<p id="par0125" class="elsevierStylePara elsevierViewall">We thank Cynthia Brown for assisting in the collection of blood samples&#46;</p>"
        "vista" => "all"
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/21735743/0000001700000004/v1_202103261153/S2173574321000538/v1_202103261153/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "43294"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Original articles"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/21735743/0000001700000004/v1_202103261153/S2173574321000538/v1_202103261153/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574321000538?idApp=UINPBA00004M"
]
Share
Journal Information

Statistics

Follow this link to access the full text of the article

Brief Report
Role of Inflammasome Activation in Systemic Lupus Erythematosus: Are Innate Immune Cells Activated?
Rol de la activación del inflammasome en lupus eritematoso sistémico: están las células del sistema inmune innato activados?
Rodolfo Perez-Alaminoa,b,
Corresponding author
ofo_pa@hotmail.com

Corresponding author.
, Raquel Cuchacovicha, Luis R. Espinozaa, Constance P. Porrettac, Arnold H. Zead
a Section of Rheumatology, Department of Internal Medicine, LSU Health Sciences Center, 1542 Tulane Avenue, New Orleans, LA 70112, USA
b Section of Rheumatology, Hospital de Clínicas Nicolás Avellaneda, Tucumán, Argentina, 2000 Catamarca Street, Tucumán, PC 4000, Argentina
c School of Medicine, Comprehensive Alcohol Research Center, 533 Bolivar Street, CSRB304, New Orleans, LA 70112, USA
d Stanley S. Scott Cancer Center, Microbiology, Immunology and Parasitology, LSU Health Sciences Center, 533 Bolivar Street, CSRB 305, New Orleans, LA 70112, USA
Read
4612
Times
was read the article
2859
Total PDF
1753
Total HTML
Share statistics
 array:23 [
  "pii" => "S2173574321000538"
  "issn" => "21735743"
  "doi" => "10.1016/j.reumae.2019.10.004"
  "estado" => "S300"
  "fechaPublicacion" => "2021-04-01"
  "aid" => "1379"
  "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and Sociedad Espa&#241;ola de Reumatolog&#237;a y Colegio Mexicano de Reumatolog&#237;a"
  "copyrightAnyo" => "2019"
  "documento" => "simple-article"
  "crossmark" => 1
  "subdocumento" => "crp"
  "cita" => "Reumatol Clin. 2021;17:187-91"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:1 [
    "total" => 0
  ]
  "itemSiguiente" => array:18 [
    "pii" => "S2173574321000381"
    "issn" => "21735743"
    "doi" => "10.1016/j.reumae.2019.07.006"
    "estado" => "S300"
    "fechaPublicacion" => "2021-04-01"
    "aid" => "1355"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and Sociedad Espa&#241;ola de Reumatolog&#237;a y Colegio Mexicano de Reumatolog&#237;a"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "fla"
    "cita" => "Reumatol Clin. 2021;17:192-6"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>"
      "titulo" => "Comparison of disease activity in patients with ankylosing spondylitis under TNFi or NSAID treatment&#44; is there any difference&#63; An observational study"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "192"
          "paginaFinal" => "196"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Comparaci&#243;n de la actividad de la enfermedad en pacientes de espondilitis anquilosante con terapia de anti-TNF o AINE&#46; &#191;Existe alguna diferencia&#63; Estudio observacional"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0010"
          "etiqueta" => "Fig&#46; 2"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr2.jpeg"
              "Alto" => 945
              "Ancho" => 2082
              "Tamanyo" => 57015
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Clinical disease activity in patients with TNFi treatment compared with those with NSAID&#46; NSAID&#58; non-steroidal anti-inflammatory drugs&#59; TNFi&#58; TNF inhibitors&#59; low disease activity&#58; BASDAI<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>4&#59; inactive disease&#58; BASDAI<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>2&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Mireia Moreno, Marta Ar&#233;valo, Marc Zamora, Caridad Pontes, Juan Carlos Oliva, Jordi Gratac&#243;s"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "Mireia"
              "apellidos" => "Moreno"
            ]
            1 => array:2 [
              "nombre" => "Marta"
              "apellidos" => "Ar&#233;valo"
            ]
            2 => array:2 [
              "nombre" => "Marc"
              "apellidos" => "Zamora"
            ]
            3 => array:2 [
              "nombre" => "Caridad"
              "apellidos" => "Pontes"
            ]
            4 => array:2 [
              "nombre" => "Juan Carlos"
              "apellidos" => "Oliva"
            ]
            5 => array:2 [
              "nombre" => "Jordi"
              "apellidos" => "Gratac&#243;s"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574321000381?idApp=UINPBA00004M"
    "url" => "/21735743/0000001700000004/v1_202103261153/S2173574321000381/v1_202103261153/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S217357432100054X"
    "issn" => "21735743"
    "doi" => "10.1016/j.reumae.2019.09.004"
    "estado" => "S300"
    "fechaPublicacion" => "2021-04-01"
    "aid" => "1370"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and Sociedad Espa&#241;ola de Reumatolog&#237;a y Colegio Mexicano de Reumatolog&#237;a"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "fla"
    "cita" => "Reumatol Clin. 2021;17:183-6"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Special Article</span>"
      "titulo" => "Pregnancy control in patients with systemic lupus erythematosus&#47;antiphospholipid syndrome&#46; Part 3&#58; Childbirth&#46; Puerperium&#46; Breastfeeding contraception&#46; Newborn"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "183"
          "paginaFinal" => "186"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Control del embarazo en pacientes con lupus eritematoso sist&#233;mico&#47;s&#237;ndrome antifosfol&#237;pido&#46; Parte 3&#46; Parto&#46; Puerperio&#46; Lactancia&#46; Anticoncepci&#243;n&#46; Reci&#233;n nacido"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Paloma Delgado, &#193;ngel Robles, Juan Antonio Mart&#237;nez L&#243;pez, Luis S&#225;ez-Comet, Esther Rodr&#237;guez Almaraz, Nuria Mart&#237;nez-S&#225;nchez, Amaia Ugarte, Paloma Vela-Casasempere, Beatriz Marco, Gerard Espinosa, Maria Galindo, Manel Casellas, Guillermo Ruiz-Irastorza, Victor Mart&#237;nez-Taboada, Jose Luis Bartha"
          "autores" => array:15 [
            0 => array:2 [
              "nombre" => "Paloma"
              "apellidos" => "Delgado"
            ]
            1 => array:2 [
              "nombre" => "&#193;ngel"
              "apellidos" => "Robles"
            ]
            2 => array:2 [
              "nombre" => "Juan Antonio"
              "apellidos" => "Mart&#237;nez L&#243;pez"
            ]
            3 => array:2 [
              "nombre" => "Luis"
              "apellidos" => "S&#225;ez-Comet"
            ]
            4 => array:2 [
              "nombre" => "Esther"
              "apellidos" => "Rodr&#237;guez Almaraz"
            ]
            5 => array:2 [
              "nombre" => "Nuria"
              "apellidos" => "Mart&#237;nez-S&#225;nchez"
            ]
            6 => array:2 [
              "nombre" => "Amaia"
              "apellidos" => "Ugarte"
            ]
            7 => array:2 [
              "nombre" => "Paloma"
              "apellidos" => "Vela-Casasempere"
            ]
            8 => array:2 [
              "nombre" => "Beatriz"
              "apellidos" => "Marco"
            ]
            9 => array:2 [
              "nombre" => "Gerard"
              "apellidos" => "Espinosa"
            ]
            10 => array:2 [
              "nombre" => "Maria"
              "apellidos" => "Galindo"
            ]
            11 => array:2 [
              "nombre" => "Manel"
              "apellidos" => "Casellas"
            ]
            12 => array:2 [
              "nombre" => "Guillermo"
              "apellidos" => "Ruiz-Irastorza"
            ]
            13 => array:2 [
              "nombre" => "Victor"
              "apellidos" => "Mart&#237;nez-Taboada"
            ]
            14 => array:2 [
              "nombre" => "Jose Luis"
              "apellidos" => "Bartha"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S1699258X19301329"
        "doi" => "10.1016/j.reuma.2019.09.004"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X19301329?idApp=UINPBA00004M"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S217357432100054X?idApp=UINPBA00004M"
    "url" => "/21735743/0000001700000004/v1_202103261153/S217357432100054X/v1_202103261153/en/main.assets"
  ]
  "en" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Brief Report</span>"
    "titulo" => "Role of Inflammasome Activation in Systemic Lupus Erythematosus&#58; Are Innate Immune Cells Activated&#63;"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "187"
        "paginaFinal" => "191"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Rodolfo Perez-Alamino, Raquel Cuchacovich, Luis R&#46; Espinoza, Constance P&#46; Porretta, Arnold H&#46; Zea"
        "autores" => array:5 [
          0 => array:4 [
            "nombre" => "Rodolfo"
            "apellidos" => "Perez-Alamino"
            "email" => array:1 [
              0 => "ofo_pa@hotmail.com"
            ]
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Raquel"
            "apellidos" => "Cuchacovich"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Luis R&#46;"
            "apellidos" => "Espinoza"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Constance P&#46;"
            "apellidos" => "Porretta"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Arnold H&#46;"
            "apellidos" => "Zea"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:4 [
          0 => array:3 [
            "entidad" => "Section of Rheumatology&#44; Department of Internal Medicine&#44; LSU Health Sciences Center&#44; 1542 Tulane Avenue&#44; New Orleans&#44; LA 70112&#44; USA"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Section of Rheumatology&#44; Hospital de Cl&#237;nicas Nicol&#225;s Avellaneda&#44; Tucum&#225;n&#44; Argentina&#44; 2000 Catamarca Street&#44; Tucum&#225;n&#44; PC 4000&#44; Argentina"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "School of Medicine&#44; Comprehensive Alcohol Research Center&#44; 533 Bolivar Street&#44; CSRB304&#44; New Orleans&#44; LA 70112&#44; USA"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Stanley S&#46; Scott Cancer Center&#44; Microbiology&#44; Immunology and Parasitology&#44; LSU Health Sciences Center&#44; 533 Bolivar Street&#44; CSRB 305&#44; New Orleans&#44; LA 70112&#44; USA"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Rol de la activaci&#243;n del inflammasome en lupus eritematoso sist&#233;mico&#58; est&#225;n las c&#233;lulas del sistema inmune innato activados&#63;"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2016
            "Ancho" => 2519
            "Tamanyo" => 277628
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Percentage of CD14<span class="elsevierStyleSup">&#43;</span>&#47;Caspase-1<span class="elsevierStyleSup">&#43;</span> expressing-cells&#46; A&#46; Cells were gated using FS vs SS to determine the &#37; of CD14<span class="elsevierStyleSup">&#43;</span>&#47;Caspase-1<span class="elsevierStyleSup">&#43;</span> cells in PBMC and Mono&#46; For lymphocytes it is only Caspase-1<span class="elsevierStyleSup">&#43;</span>&#46; Data from 14 SLE patients and 13 normal controls are presented&#44; as the mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#46; B&#46; Representative data from 1 normal control and 1 SLE patient dot plot showing the expression of CD14<span class="elsevierStyleSup">&#43;</span> vs&#46; Caspase-1<span class="elsevierStyleSup">&#43;</span> in PBMC &#40;1&#41;&#44; Lymph &#40;2&#41; and Mono &#40;3&#41;&#46; Stained cells were gated based on FSC and SSC parameters &#40;capase-1<span class="elsevierStyleSup">&#43;</span> lymphocytes in Q1 and PMBC and monocytes in Q2&#41;&#46; PBMC&#58; peripheral blood mononuclear cells&#59; Lym&#58; lymphocytes&#59; Mono&#58; monocytes&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Systemic lupus erythematosus &#40;SLE&#41; is a prototype of autoimmune disease&#44; characterized by a wide spectrum of clinical and immunologic abnormalities&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Exciting data have emerged over the last few years&#44; regarding the role of the inflammasome as an important component of the innate immune system&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2&#8211;4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The inflammasome is a large molecular platform constituted by a group of cytoplasmic protein complexes that senses a diverse set of inflammation-inducing stimuli&#44; including pathogen-associated molecular patterns &#40;PAMPs&#41;&#44; predominantly found in microbes and damage-associated molecular patterns &#40;DAMPs&#41; that are released as a result of perturbations of tissue homeostasis caused by microbial or non-microbial insults&#46; The central components of the inflammasome include&#58; &#40;1&#41; scaffold of the NOD-like receptors &#40;NLR&#41; family&#58; NLRP1&#44; NLRP3&#44; NLRC4 and AIM2&#59; &#40;2&#41; apoptosis associated speck-like protein containing a CARD &#40;ASC&#41;&#59; and &#40;3&#41; pro-Caspase-1&#46; The activated sensor can then recruit the other components of the inflammasome&#44; leading to the formation of the multiprotein complex containing pro-Caspase-1&#46; The assembly of these components leads to the autoproteolytic activation of Caspase-1&#44; which converts an immature IL-1&#946; and IL-18 to a mature secreted form&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">5&#8211;7</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Because the precise etiology and mechanisms leading to aberrant immune responses in SLE are not yet clearly understood&#44; we hypothesized that&#58; &#8220;inflammasome activation occurs in monocytes&#44; as a key element on the initiation and amplification of the innate immune response in SLE pathogenesis&#8221;&#46; Therefore&#44; the aims of this study were&#58; &#40;1&#41; To determine whether inflammasome activation occurs in monocytes of SLE patients&#59; and &#40;2&#41; to determine the relationship between the production of inflammasome related-cytokines and disease activity in these patients&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Patients selection</span><p id="par0025" class="elsevierStylePara elsevierViewall">Consecutive patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41; who fulfilled the revised ACR criteria for SLE were enrolled at Louisiana State University &#40;LSU&#41; outpatient Rheumatology clinics&#46; Consecutive patients without any inflammatory rheumatic disease were included as healthy controls &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#41;&#44; matched by age&#44; sex and ethnicity&#46; Patients with acute and&#47;or chronic infections&#44; including history of positive serology to HIV&#44; HBV and HCV were excluded&#46; All participants signed an informed consent form prior to their inclusion&#44; which was approved by LSU Institutional Review Board&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Demographic&#44; laboratory&#44; and clinical data were recorded&#46; Lupus disease activity was assessed by SELENA-SLEDAI score&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> A score &#8805;4 was defined as active disease&#46; Lupus nephritis &#40;LN&#41; &#40;absent&#44; past&#44; current&#41; was also recorded&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Collection and processing of blood samples</span><p id="par0035" class="elsevierStylePara elsevierViewall">Peripheral blood mononuclear cells &#40;PBMCs&#41; from patients and controls were isolated by Ficoll density gradient centrifugation &#40;Sigma Chemicals Co&#46;&#44; St Louis&#44; MO&#44; USA&#41;&#46; CD14<span class="elsevierStyleSup">&#43;</span> monocytes were purified from PBMCs&#44; using an autoMACS Separator and an autoMACS CD14<span class="elsevierStyleSup">&#43;</span> negative selection kit &#40;Miltenyi Biotec&#44; Germany&#41;&#46; Purified monocytes were cultured in six well plates &#40;1<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">6</span><span class="elsevierStyleHsp" style=""></span>monocytes&#47;well&#41; in RPMI 1640&#44; supplemented with 10&#37; fetal bovine serum&#44; 10<span class="elsevierStyleHsp" style=""></span>mM HEPES and 2<span class="elsevierStyleHsp" style=""></span>mM <span class="elsevierStyleSmallCaps">l</span>-Glutamine&#46; After cell adherence&#44; monocytes were stimulated &#40;&#8764;18<span class="elsevierStyleHsp" style=""></span>h&#41; with lipopolysaccharide &#40;LPS&#41; &#40;100<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41; in presence or absence of Caspase-1 inhibitor &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;M&#41; &#40;Caspase-1 inhibitor I&#44; cell-permeable&#44; YVAD-CHO&#41; &#40;Calbiochem&#44; Germany&#41;&#46; The remaining supernatants were stored at &#8722;70<span class="elsevierStyleHsp" style=""></span>&#176;C until assayed&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Intracellular Caspase-1 detection</span><p id="par0040" class="elsevierStylePara elsevierViewall">Fresh PBMCs were fixed-permeabilized&#44; and stained with CD14<span class="elsevierStyleSup">&#43;</span> &#40;FITC&#41; &#40;Beckman Coulter&#44; USA&#41; and Caspase-1 &#40;A-19&#41; &#40;PE&#41; antibodies &#40;Santa Cruz Biotechnology&#44; USA&#41;&#46; Caspase-1 expression was measured by flow cytometry on a BD FACSCantor II flow cytometer &#40;Becton Dickinson&#44; San Jose&#44; CA&#41;&#46; Log fluorescence of the gated population was measured and 20&#44;000 cells were acquired for each sample&#46; Caspase-1 expression corresponded to the average of 2 determinations made for each patient and control&#46; Data analysis was performed using BD FACSDiva software version 6&#46;1&#46;3&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Cytokine measurement</span><p id="par0045" class="elsevierStylePara elsevierViewall">IL-1&#946; and IL-18 levels were determined in patients plasma and cell culture supernatants by human Quantikine ELISA kits &#40;R&#38;D Systems&#44; USA&#41;&#44; following the manufacturer&#39;s instructions&#46; Since the assay range for IL-1&#946; is between 3&#46;9 and 250<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#44; we extended down the lower range of the standards 3 dilutions giving us a range between 0&#46;100&#8211;250<span class="elsevierStyleHsp" style=""></span>pg&#47;ml to maximize the presence of low values in our samples&#46; These extra dilutions did not alter the linearity of the standard curve&#46; Plasmatic cytokine levels of IL-1beta and IL-18 corresponded to the average of 2 determinations made for each patient and control&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0050" class="elsevierStylePara elsevierViewall">Descriptive values of variables were expressed as the mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#46; Variables with normal distribution were analyzed by Student&#39;s <span class="elsevierStyleItalic">t</span>-test and those with non-normal distribution were analyzed with Mann&#8211;Whitney test&#46; <span class="elsevierStyleItalic">p</span>-Values less than 0&#46;05 were considered significant&#46; The statistical analysis was carried out using GraphPad Prism software &#40;version 5&#46;0&#41;&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall">Fourteen &#40;14&#41; consecutive SLE patients were included in the study&#46; Thirteen out of 14 patients &#40;93&#37;&#41; were female and 8&#47;14 &#40;57&#37;&#41; were African-Americans&#46; The mean age of the patients at the time of the study was 32&#46;7 &#40;&#177;9&#46;1&#41; years&#44; and the mean disease duration was 8&#46;9 years &#40;&#177;6&#46;4&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#44; the percentage of CD14<span class="elsevierStyleSup">&#43;</span> vs&#46; Caspase-1<span class="elsevierStyleSup">&#43;</span> expression was found to be significantly higher in fresh PBMCs and in the monocytic population from SLE patients compared to normal controls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#44; respectively&#41;&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B shows the percentage of Caspase-1 positive cells in PBMCs and monocytes &#40;<span class="elsevierStyleItalic"><span class="elsevierStyleBold">quadrant 2</span></span>&#41; from one control and one SLE-patient&#46; The majority of Caspase-1 positive cells were observed in the monocytic population from patients with SLE &#40;68&#46;4&#37;&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Interestingly&#44; the increased numbers of Caspase-1 positive cells directly paralleled with significantly higher plasma levels of IL-1&#946; &#40;2&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;05<span class="elsevierStyleHsp" style=""></span>pg&#47;ml vs&#46; 1&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;10<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;008&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41; and IL-18 &#40;725&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>215&#46;4<span class="elsevierStyleHsp" style=""></span>pg&#47;ml vs&#46; 479&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>125&#46;2<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; in SLE patients when compared to normal controls &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#46; Furthermore&#44; we observed that levels of IL-18 were significantly higher &#40;834&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>179&#46;3<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; in patients presenting high disease activity &#40;SELENA-SLEDAI &#8805;6&#41;&#44; compared to patients with mild disease or remission &#40;572&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>171&#46;6<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; No statistical differences in levels of IL-1&#946; were observed between SLE patients with high vs&#46; mild disease activity &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>A and B&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Compared to normal controls&#44; purified monocytes from SLE patients displayed a robust inflammatory response when cultured in vitro&#46; As shown in <a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>A&#44; when monocytes from normal controls and SLE patients were stimulated with LPS&#44; there was a 60 &#40;mean&#58; 4597<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3515<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; and 100 &#40;mean&#58; 8895<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3475<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; fold increase in IL-1&#946; compared to non-stimulated monocytes &#40;mean&#58; 88&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;8&#41;&#46; No significant differences in IL1-&#946; production were observed between LPS-stimulated monocytes from controls and SLE patients&#46; Similar production pattern of IL-18 was observed &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>B&#41;&#44; where the mean of IL-18 production was significantly higher &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; in supernatants from stimulated monocytes from SLE-patients &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; than in non-stimulated&#46; Furthermore&#44; IL-18 production in LPS-stimulated monocytes from SLE patients was 3 fold higher when compared to normal controls &#40;mean&#58; 103&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>213&#46;2<span class="elsevierStyleHsp" style=""></span>pg&#47;ml and 30&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#46;9<span class="elsevierStyleHsp" style=""></span>pg&#47;ml respectively&#41;&#46; In <a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>A&#44; there was a slight reduction in IL-1&#946; production in LPS-stimulated normal monocytes plus the inhibitor&#44; that was not observed in SLE patients&#46; In contrast&#44; as seen in <a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>B&#44; a reduction of approximately 3 fold in IL-18 production was observed in supernatants of LPS-stimulated monocytes from SLE patients plus inhibitor&#46; Significant correlations between Caspase-1 expression&#47;cytokine production and clinical manifestations&#44; treatment or serologic markers of the disease were not found in this study&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">The major finding of this pilot study is that in vitro&#44; monocytes from SLE patients showed an increased expression of Caspase-1 that parallels with significant higher levels of inflammasome-related cytokines&#44; IL-1&#946; and IL-18&#44; in patients with SLE as compared to healthy subjects&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">How the inflammasome is triggered and activated in SLE&#44; has become an important concept to understand its role in this disease&#46; Immune complexes formed secondary to antibody recognition of DNA or RNA antigens&#44; have been shown to stimulate inflammasome activation through up-regulation of TLR-dependent activation of NF&#954;&#946; and subsequent activation of the NLRP3 inflammasome&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">9&#44;10</span></a> C3a&#44; which is released during complement activation in tissues&#44; promotes inflammasome activation through up-regulation of ATP secretion&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> Neutrophil extracellular traps &#40;NETs&#41; have also been proposed to play a pathogenic role in SLE&#46; Recently&#44; NETs have been shown to activate caspase-1&#44; resulting in release of IL-1&#946; and IL-18&#44; and this activation was enhanced in macrophages derived from SLE patients&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Because innate immune cells are crucial for the onset of the immune response&#44; inflammasome activation in these cells may promote the initiation and amplification of the autoimmune response&#46; In this study&#44; we found an increased expression of Caspase-1 in monocytes from SLE patients&#44; as compared with healthy controls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#46; To our knowledge this is the first study in demonstrating that basal inflammasome activation occurs in fresh isolated monocytes from SLE patients&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">IL-1&#946; and IL-18 cytokines&#44; hallmarks of inflammasome activation&#44; belong to the IL-1 cytokine family&#46; IL-1&#946; is critical to the pathology of most autoinflammatory and many autoimmune diseases&#46; IL-18 was discovered initially as an IFN-&#947; inducing factor&#44; and since then has been known as a prototypical Th-1 cytokine&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> In our study&#44; plasma levels of these cytokines were found to be significantly higher in SLE patients as compared to normal controls&#46; Recently&#44; Liu et al&#46; have also shown an enhanced inflammasome activity in SLE patients&#44; mediated by type I IFN&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">In this study&#44; we focused on investigating the capacity of monocytes from SLE patients to secrete inflammasome-related cytokines at the basal level&#44; and in response to the inflammatory stimuli LPS&#44; as compared with monocytes from healthy individuals&#46; As expected&#44; monocytes from SLE patients displayed a robust inflammatory response after LPS stimulation&#44; characterized by elevated levels of IL-1&#946; and IL-18 when compared to stimulated monocytes from healthy individuals&#46; In addition&#44; the production of IL-18 was reduced by almost 3 fold when Caspase-1 inhibitor was added to the cultures&#46; There was also a reduction in levels of IL-1&#946; in supernatants treated with Caspase-1 inhibitor&#44; although in less extent compared to IL-18&#46; A possible explanation might be related by the extraordinary high amount of IL-1&#946; released&#44; as compared to IL-18&#46; The inhibitor is competitive&#44; so inhibition could be overcome by substrate excess&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">A growing body of evidence supports the pivotal role of infections in the induction or exacerbation of SLE&#46; Infections can be responsible for aberrant immune response leading to a loss of tolerance toward native proteins&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a> Our findings suggest that monocytes from SLE patients might have an abnormal expression of IL-18 and IL-1&#946;-regulating molecules in response to infection&#44; thus resulting in anomalous activation of adaptive immune responses&#44; which can be the basis by which SLE develops and flares&#46; On the other hand&#44; we also agree that the main limitation of the study is the small number of the sample&#46; However&#44; despite this&#44; we were able to demonstrate the activation of the inflammasome in monocytes of SLE patients&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">In conclusion&#44; our study shows that monocytes from SLE patients exhibit an enhanced activation of the inflammasome complex in vitro&#44; which is the product of elevated expression of Caspase-1 and inflammasome-related cytokines&#46; The results of this proof of concept study indicate a potential role of the inflammasome pathway in the pathogenesis of SLE&#44; thus identifying a novel pathway for therapeutic targeting&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Ethical approval</span><p id="par0110" class="elsevierStylePara elsevierViewall">All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and&#47;or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Informed consent</span><p id="par0115" class="elsevierStylePara elsevierViewall">Informed consent was obtained from all individual participants included in the study&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflict of interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest to disclose&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:13 [
        0 => array:3 [
          "identificador" => "xres1489849"
          "titulo" => "Abstract"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Background"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "Methods"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "Results"
            ]
            3 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Conclusions"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1352808"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres1489850"
          "titulo" => "Resumen"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Introducci&#243;n"
            ]
            1 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "Objetivos"
            ]
            2 => array:2 [
              "identificador" => "abst0035"
              "titulo" => "Materiales y m&#233;todos"
            ]
            3 => array:2 [
              "identificador" => "abst0040"
              "titulo" => "Resultados"
            ]
            4 => array:2 [
              "identificador" => "abst0045"
              "titulo" => "Conclusiones"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec1352809"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Materials and methods"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Patients selection"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Collection and processing of blood samples"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Intracellular Caspase-1 detection"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Cytokine measurement"
            ]
            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Statistical analysis"
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Results"
        ]
        7 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Ethical approval"
        ]
        9 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Informed consent"
        ]
        10 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Conflict of interest"
        ]
        11 => array:2 [
          "identificador" => "xack521618"
          "titulo" => "Acknowledgements"
        ]
        12 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2019-05-30"
    "fechaAceptado" => "2019-10-17"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1352808"
          "palabras" => array:6 [
            0 => "Systemic lupus erythematosus"
            1 => "Pathogenesis"
            2 => "Inflammasomes"
            3 => "Innate immunity"
            4 => "Caspase-1"
            5 => "Cytokines"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1352809"
          "palabras" => array:6 [
            0 => "Lupus eritematoso sist&#233;mico"
            1 => "Patog&#233;nesis"
            2 => "Inflamasoma"
            3 => "Inmunidad innata"
            4 => "Caspasa-1"
            5 => "Citoquinas"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Systemic lupus erythematosus &#40;SLE&#41; is characterized by a wide spectrum of clinical and immunological abnormalities&#46; New data have emerged about the role of inflammasomes in autoimmune diseases&#46; We aimed to investigate whether basal inflammasome activation occurs in SLE patients&#44; and whether a relationship between inflammasome-related-cytokines and disease activity exists&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Fourteen &#40;14&#41; consecutive SLE patients and 13 healthy individuals&#44; matched by sex&#44; age and ethnicity&#44; were included&#46; Demographics&#44; laboratory and clinical data were recorded&#46; Peripheral blood mononuclear cells &#40;PBMCs&#41; from patients and controls were obtained and monocytes were isolated by negative selection&#46; Purified monocytes were stimulated with LPS in the presence or absence of Caspase-1 inhibitor&#46; CD14 and Caspase-1 expression were analyzed by flow cytometry&#46; Cytokine levels were determined in plasma and culture supernatants by ELISA&#46; Student&#39;s <span class="elsevierStyleItalic">t</span> test and Mann&#8211;Whitney tests were used for statistical analysis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The percentage of CD14<span class="elsevierStyleSup">&#43;</span>&#47;Caspase-1<span class="elsevierStyleSup">&#43;</span> was significantly higher in monocytes from SLE patients compared to normal controls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46; These findings paralleled with higher plasma levels of IL-1&#946; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; and IL-18 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; in those patients&#46; Purified monocytes from SLE patients displayed a robust inflammatory response after LPS stimulation where Caspase-1&#44; IL-1&#946; and IL-18 were highly expressed&#46; Plasma levels of IL-18 were also significantly higher in SLE patients with active disease &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; In addition&#44; the production of IL-18 was reduced by 3 fold when Caspase-1 inhibitor was added to the cultures&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Monocytes from SLE patients exhibited increased inflammasome activation&#44; characterized by high expression of Caspase-1&#44; IL-1&#946; and IL-18&#46; Caspase-1 specific inhibitor decreased inflammasome activation &#40;in vitro&#41; by suppressing the production of IL-18&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El lupus eritematoso sist&#233;mico &#40;LES&#41; se caracteriza por presentar diversas anormalidades cl&#237;nicas e inmunol&#243;gicas&#46; El ensamblaje de los componentes del inflamasoma da lugar a la activaci&#243;n de caspasa-1&#44; generando la liberaci&#243;n de citoquinas pro-inflamatorias IL-1&#946; e IL-18&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Objetivos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Evaluar si existe una activaci&#243;n basal del inflamasoma en pacientes con LES y determinar la asociaci&#243;n de las citoquinas IL-1&#946; e IL-18 con la actividad de la enfermedad&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Materiales y m&#233;todos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 14 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41; pacientes consecutivos con LES y 13 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#41; controles&#44; pareados por edad&#44; sexo y raza&#46; Se recogieron datos cl&#237;nicos&#44; demogr&#225;ficos y de laboratorio&#46; Los monocitos fueron aislados a partir de c&#233;lulas mononucleares de sangre perif&#233;rica obtenidas de pacientes y controles&#46; Los monocitos purificados fueron estimulados con LPS&#44; en presencia y ausencia de inhibidor de caspasa-1&#46; La expresi&#243;n de CD14 y caspasa-1 fueron determinados por citometr&#237;a de flujo&#46; Niveles de citoquinas fueron determinadas en plasma y en sobrenadantes de cultivos mediante t&#233;cnica de ELISA&#46; Test de Student y Mann-Whitney fueron usados para el an&#225;lisis estad&#237;stico&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El porcentaje de CD14<span class="elsevierStyleSup">&#43;</span>&#47;caspasa-1<span class="elsevierStyleSup">&#43;</span> fue significativamente superior en monocitos de pacientes con LES vs&#46; controles &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#46; En forma paralela&#44; se encontraron niveles plasm&#225;ticos significativamente superiores de IL-1&#946; &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41; y de IL-18 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41; en pacientes con LES&#46; Monocitos purificados de pacientes l&#250;picos presentaron una robusta respuesta inflamatoria luego de ser estimulados con LPS&#44; donde caspasa-1&#44; IL-1&#946; e IL-18 fueron altamente expresados&#46; Niveles plasm&#225;ticos de IL-18 fueron significativamente mayores en pacientes con LES y enfermedad activa &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46; Por otro lado&#44; la producci&#243;n de IL-18 se redujo casi 3 veces cuando se agreg&#243; inhibidor de caspasa-1 en cultivos&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusiones</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Monocitos de pacientes con LES presentaron evidencia de activaci&#243;n de componentes del inflamasoma&#44; caracterizada por una mayor expresi&#243;n de caspasa-1&#44; IL-1&#946; e IL-18&#46; El inhibidor espec&#237;fico de caspasa-1 disminuy&#243; la activaci&#243;n del inflamasoma <span class="elsevierStyleItalic">in vitro&#44;</span> reduciendo la producci&#243;n de IL-18&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introducci&#243;n"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Objetivos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Materiales y m&#233;todos"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Resultados"
          ]
          4 => array:2 [
            "identificador" => "abst0045"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "multimedia" => array:4 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2016
            "Ancho" => 2519
            "Tamanyo" => 277628
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Percentage of CD14<span class="elsevierStyleSup">&#43;</span>&#47;Caspase-1<span class="elsevierStyleSup">&#43;</span> expressing-cells&#46; A&#46; Cells were gated using FS vs SS to determine the &#37; of CD14<span class="elsevierStyleSup">&#43;</span>&#47;Caspase-1<span class="elsevierStyleSup">&#43;</span> cells in PBMC and Mono&#46; For lymphocytes it is only Caspase-1<span class="elsevierStyleSup">&#43;</span>&#46; Data from 14 SLE patients and 13 normal controls are presented&#44; as the mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#46; B&#46; Representative data from 1 normal control and 1 SLE patient dot plot showing the expression of CD14<span class="elsevierStyleSup">&#43;</span> vs&#46; Caspase-1<span class="elsevierStyleSup">&#43;</span> in PBMC &#40;1&#41;&#44; Lymph &#40;2&#41; and Mono &#40;3&#41;&#46; Stained cells were gated based on FSC and SSC parameters &#40;capase-1<span class="elsevierStyleSup">&#43;</span> lymphocytes in Q1 and PMBC and monocytes in Q2&#41;&#46; PBMC&#58; peripheral blood mononuclear cells&#59; Lym&#58; lymphocytes&#59; Mono&#58; monocytes&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 2082
            "Ancho" => 1447
            "Tamanyo" => 266251
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Plasma levels of inflammasome-related cytokines&#46; A and B&#46; IL-1&#946; and IL-18 level in the plasma of &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#41; normal controls and &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41; SLE patients were determined by ELISA&#46; IL1&#946; and IL-18 were significantly high expressed in SLE patients compared to normal controls&#46; Data are presented as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD from duplicates&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 2342
            "Ancho" => 1578
            "Tamanyo" => 311622
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Plasma levels of inflammasome-related cytokines and disease activity&#46; A and B&#46; Plasmatic levels of IL-1&#946; and IL-18 were tested by ELISA in &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41; SLE patients in remission and &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41; SLE patients with active disease &#40;SLEDAI<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>4&#41;&#46; Data are presented as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD from duplicates&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Fig&#46; 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 2382
            "Ancho" => 1457
            "Tamanyo" => 192314
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">LPS induces secretion of high levels of IL-1&#946; and IL-18 in monocytes from SLE patients&#46; Purified CD14<span class="elsevierStyleSup">&#43;</span> monocytes were incubated with LPS &#40;100<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41;&#44; in the presence or absence of Caspase-1 inhibitor &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;M&#41;&#46; IL-1&#946; &#40;A&#41; and IL-18 &#40;B&#41; concentrations were measured in supernatants by specific ELISA after &#8764;18-h incubation&#46; Data is representative as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD from duplicates&#46; NS&#58; Non-stimulated&#59; LPS&#58; lipopolysaccharide&#59; Inh&#58; Caspase-1 inhibitor&#59; SLE&#58; systemic lupus erythematosus&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:15 [
            0 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The pathogenesis of systemic lupus erythematosus-an up-date"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46; Choi"
                            1 => "S&#46; Taek Kim"
                            2 => "J&#46; Craft"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.coi.2012.10.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Opin Immunol"
                        "fecha" => "2012"
                        "volumen" => "24"
                        "paginaInicial" => "651"
                        "paginaFinal" => "657"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23131610"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inflammasomes and rheumatic diseases&#58; evolving concepts"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "P&#46; Sidiropoulos"
                            1 => "G&#46; Goulielmos"
                            2 => "G&#46; Voloudakis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2007.078014"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2008"
                        "volumen" => "67"
                        "paginaInicial" => "1382"
                        "paginaFinal" => "1389"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17921182"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inflammasomes and autoimmunity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "P&#46; Shaw"
                            1 => "M&#46;F&#46; McDermott"
                            2 => "T&#46;D&#46; Kanneganti"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.molmed.2010.11.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Trends Mol Med"
                        "fecha" => "2010"
                        "volumen" => "17"
                        "paginaInicial" => "57"
                        "paginaFinal" => "64"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21163704"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inflammatory Caspase-1s&#58; linking an intracellular innate immune system to autoinflammatory diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "F&#46; Martinon"
                            1 => "J&#46; Tschopp"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cell.2004.05.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell"
                        "fecha" => "2004"
                        "volumen" => "117"
                        "paginaInicial" => "561"
                        "paginaFinal" => "574"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15163405"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inflammasomes in health and disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "T&#46; Strowig"
                            1 => "J&#46; Henao-Mejia"
                            2 => "E&#46; Elinav"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nature10759"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nature"
                        "fecha" => "2012"
                        "volumen" => "481"
                        "paginaInicial" => "278"
                        "paginaFinal" => "286"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22258606"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The inflammasomes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "K&#46; Schroder"
                            1 => "J&#46; Tschopp"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cell.2010.01.040"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell"
                        "fecha" => "2010"
                        "volumen" => "140"
                        "paginaInicial" => "821"
                        "paginaFinal" => "832"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20303873"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The role of inflammasome-derived IL-1 in driving IL-17 responses"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "K&#46; Mills"
                            1 => "L&#46; Dungan"
                            2 => "S&#46; Jones"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1189/jlb.0812424"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Leukoc Biol"
                        "fecha" => "2013"
                        "volumen" => "93"
                        "paginaInicial" => "1"
                        "paginaFinal" => "9"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23284088"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Derivation of the SLEDAI&#46; A disease activity index for lupus patients&#46; The Committee on Prognosis Studies in SLE"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "C&#46; Bombardier"
                            1 => "D&#46;D&#46; Gladman"
                            2 => "M&#46;B&#46; Urowitz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.1780350606"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "1992"
                        "volumen" => "35"
                        "paginaInicial" => "630"
                        "paginaFinal" => "640"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1599520"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46; Baroja-Mazo"
                            1 => "F&#46; Martin-Sanchez"
                            2 => "A&#46;I&#46; Gomez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ni.2919"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Immunol"
                        "fecha" => "2014"
                        "volumen" => "15"
                        "paginaInicial" => "738"
                        "paginaFinal" => "748"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24952504"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Self Double-Stranded &#40;ds&#41; DNA induces IL-1&#946; production from human monocytes by activating NLRP3 inflammasome in the presence of anti-dsDNA antibodies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "M&#46;S&#46; Shin"
                            1 => "Y&#46; Kang"
                            2 => "N&#46; Lee"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "2013"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8759771"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "C3a modulates IL-1&#946; secretion in human monocytes by regulating ATP efflux and subsequent NLRP3 inflammasome activation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "E&#46; Asgari"
                            1 => "G&#46; Le Friec"
                            2 => "H&#46; Yamamoto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2013-05-502229"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2013"
                        "volumen" => "122"
                        "paginaInicial" => "3473"
                        "paginaFinal" => "3481"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23878142"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neutrophil extracellular trap-associated protein activation of the NLRP3 inflammasome is enhanced in lupus macrophages"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46;M&#46; Kahlenberg"
                            1 => "C&#46; Carmona-Rivera"
                            2 => "C&#46;K&#46; Smith"
                            3 => "M&#46;J&#46; Kaplan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4049/jimmunol.1202388"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "2013"
                        "volumen" => "190"
                        "paginaInicial" => "1217"
                        "paginaFinal" => "1226"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23267025"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The IL-1 family&#58; regulators of immunity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;E&#46; Sims"
                            1 => "D&#46;E&#46; Smith"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nri2691"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Immunol"
                        "fecha" => "2010"
                        "volumen" => "10"
                        "paginaInicial" => "89"
                        "paginaFinal" => "102"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20081871"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Enhanced inflammasome activity in systemic lupus erythematosus is mediated via type I interferon-induced up-regulation of interferon regulatory factor 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46; Liu"
                            1 => "C&#46;C&#46; Berthier"
                            2 => "J&#46;M&#46; Kahlenberg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.40166"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheumatol"
                        "fecha" => "2017"
                        "volumen" => "69"
                        "paginaInicial" => "1840"
                        "paginaFinal" => "1849"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28564495"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Infections as triggers and complications of systemic lupus erythematosus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46; Doria"
                            1 => "M&#46; Canova"
                            2 => "M&#46; Tonon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.autrev.2008.07.019"
                      "Revista" => array:6 [
                        "tituloSerie" => "Autoimmun Rev"
                        "fecha" => "2008"
                        "volumen" => "8"
                        "paginaInicial" => "24"
                        "paginaFinal" => "28"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18703174"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
    "agradecimientos" => array:1 [
      0 => array:4 [
        "identificador" => "xack521618"
        "titulo" => "Acknowledgements"
        "texto" => "<p id="par0125" class="elsevierStylePara elsevierViewall">We thank Cynthia Brown for assisting in the collection of blood samples&#46;</p>"
        "vista" => "all"
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/21735743/0000001700000004/v1_202103261153/S2173574321000538/v1_202103261153/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "43294"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Original articles"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/21735743/0000001700000004/v1_202103261153/S2173574321000538/v1_202103261153/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574321000538?idApp=UINPBA00004M"
]
Article information
ISSN: 21735743
Original language: English
The statistics are updated each day
Year/Month Html Pdf Total
2024 November 7 9 16
2024 October 36 106 142
2024 September 46 110 156
2024 August 75 95 170
2024 July 53 86 139
2024 June 55 92 147
2024 May 70 101 171
2024 April 69 100 169
2024 March 39 108 147
2024 February 42 109 151
2024 January 30 83 113
2023 December 32 84 116
2023 November 48 98 146
2023 October 36 76 112
2023 September 98 115 213
2023 August 105 83 188
2023 July 33 83 116
2023 June 30 82 112
2023 May 39 93 132
2023 April 18 68 86
2023 March 60 82 142
2023 February 48 76 124
2023 January 45 81 126
2022 December 60 95 155
2022 November 39 87 126
2022 October 58 38 96
2022 September 40 53 93
2022 August 35 57 92
2022 July 39 45 84
2022 June 43 61 104
2022 May 51 43 94
2022 April 41 51 92
2022 March 50 61 111
2022 February 55 54 109
2022 January 42 45 87
2021 December 26 50 76
2021 November 26 44 70
2021 October 30 54 84
2021 September 4 1 5
Show all

Follow this link to access the full text of the article

Idiomas
Reumatología Clínica (English Edition)
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?