Original Article
Association of anti-Ro52, anti-Ro60 and anti-La antibodies with diagnostic, clinical and laboratory features in a referral hospital in Jerez, Spain
Asociación de los anticuerpos anti-Ro52, anti-Ro60 y anti-La con las características diagnósticas, clínicas y de laboratorio en un hospital de referencia en Jerez, España
Raúl Menor Almagroa,
, Aurora Jurado Rogerb, Francisco Javier Rodríguez Gutiérrezc, Rocío Solís Díazd, Mario Humberto Cardiele, José Javier Salaberri Maestrojuana
Corresponding author
a Dept. of Rheumatology, Hospital de Jerez, Jerez de la Frontera, Spain
b Dept. of Immunology, Hospital Reina Sofía, Córdoba, Spain
c Dept. of Immunology, Hospital de Jerez, Jerez de la Frontera, Spain
d Hospital Comarcal Virgen del Camino, Sanlucar, Spain
e Centro de Investigación Clínica de Morelia SC, Morelia, Mexico
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array:3 [ "entidad" => "Hospital Comarcal Virgen del Camino, Sanlucar, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Centro de Investigación Clínica de Morelia SC, Morelia, Mexico" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Asociación de los anticuerpos anti-Ro52, anti-Ro60 y anti-La con las características diagnósticas, clínicas y de laboratorio en un hospital de referencia en Jerez, España" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1720 "Ancho" => 2651 "Tamanyo" => 147282 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Cluster analysis to identify cluster of antibodies in our sample of patients.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Autoimmune diseases represent a wide variety of clinical problems affecting multiple organs and systems, and affect as least 5% of the population.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> A great diversity of antibodies has been associated with different clinical manifestations and clinicians have relied on them guiding clinical diagnosis, prognostic implications, and in some cases therapeutic decisions.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2,3</span></a> Current knowledge on pathogenesis of autoimmune diseases agrees that a complex interaction of genes and environmental features are needed for them to appear.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Combination of line immunoblot ENA assay (INNOLIA-ANA) and indirect immunofluorescence techniques to detect antinuclear antibodies in HEp-2 cells as substrate are good screening methods in patients with a clinical suspicion of an autoimmune disease, mainly systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). Although false positive results can occur, titers >1:80 suggest the possibility of an autoimmune disorder and should prompt ordering more specific evaluations to determine specific reactivities of the antinuclear antibodies (ANA) such as anti-double stranded DNA and extractable nuclear antigens (ENA).<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Ro/SSA and La/SSB are heterogeneous antigenic complexes formed by three different proteins (Ro-52, Ro-60 and La) and four YRNA particles. The Ro60 protein acts as a quality check point for RNA misfolded with molecular chaperones for defective RNAs. The misfolded RNAs are recognized and then tagged by Ro60 for degradation. Ro52 interacts with different molecules, among them calreticulin and the immunoglobulin heavy chain-binding protein. Ro52 is thought to modify the role or stability of its substrates through ubiquitination, and this modification might result in the Ro52 mediated biological events.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Anti-Ro/SSA and anti-La/SSB antibodies have been described in various autoimmune diseases. In primary Sjögren's syndrome (pSS) circulating antibodies are detected in approximately 60–70% of patients, and higher levels have been associated with early disease onset and systemic manifestations.<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">7,8</span></a> GEMESS Study Group, which included 12 reference centers in Spain, confirmed these clinical and laboratory features in a cohort of patients with pSS, and observed decreased levels of C4 in patients with early disease onset.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Anti-Ro/SSA are detected in 30% of patients with SLE diagnosis, particularly (90%) those subtypes with late onset, subacute cutaneous lupus erythematosus, drug induced lupus and congenital deficiencies of C2, C4 and C1q, also in patients with SS/SLE overlap syndrome and undifferentiated connective tissue disease.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a> In contrast, anti-La/SSB is more commonly associated with SS,<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a> and strongly correlated in anti-La/SSB positive with anti-Ro/SSA negative to organ dysfunction (kidney, lung, liver).<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Since the eighties, development of congenital heart blockade has been described in autoimmune diseases, such as SS and SLE. However cardiac involvement is more related to circulating antibodies from the mother rather than the diagnosis of autoimmune disease. Although the immune profile is variable among different studies the anti-Ro52 antibody is more common in mothers of children with congenital cardiac blockade, neonatal lupus, and neonates with prolonged QT without congenital cardiac blockade.<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">10,13,14</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Prevalence and clinical associations of anti-Ro/SSA and anti-La/SSB antibodies may vary in different ethnic groups. In addition to studies conducted in the Spanish population on immune expression of SS, other studies have been developed in recent years on the immune profile of patients with anti-Ro52, anti-Ro60 and anti-La antibodies. Most of them have been performed on specific diagnosis of connective tissue disorders. In a cohort of patients with pSS developed in Korea associations of these antibodies with different clinical manifestations were observed. Anti-Ro52 was the most frequent autoantibody and related with liver and muscle damage.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a> A recent study in the Mexican population to determine the prevalence of pSS in recent-onset SLE showed the presence of anti-Ro/SSA as a predictor of overlap, while the absence of anti-Ro/SSA, anti-La/SSB and rheumatoid factor was related to the lowest risk of overlap.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> Finally, the Ghent University Hospital proposed a study to determine the diagnostic distribution associated with serotype of anti-Ro/SSA or anti-La/SSB in consecutive patients referred to the rheumatology laboratory. SLE was associated to anti-Ro60 positive and isolated anti-La predisposed more to pSS.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">We undertook this study to evaluate clinical, laboratory and diagnosis associations of this important subset of antibodies at a hospital in Spain.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Research center</span><p id="par0045" class="elsevierStylePara elsevierViewall">Hospital de Jerez de la Frontera is a regional specialty center located in Southwestern Spain. It provides specialized clinical services and has 550 beds. Its Immunology Department analyzes around 5800 ANA test and 1700 immunoblot ENA assay per year in a population of 450,000 inhabitants. Among its laboratory personnel are a biologist and an immunologist who perform specialized tests for different departments. Any practicing clinician can order antinuclear antibodies tests but they are mainly requested by rheumatologists, followed by primary care physicians, gastroenterologists, internists, nephrologists, pneumologists and hematologists.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Samples</span><p id="par0050" class="elsevierStylePara elsevierViewall">A computerized registry of laboratory results is available since June 2002. We retrospectively analyzed all consecutive samples ordering ANA test from June 2002 to December 2012. Sera with titter at least 1:160 by immunofluorescence assay on HEp-2 cells (Euroimmun, Germany) were considered positive and performed by a single trained observer. Those sera with a positive ANA test for this titer dilution were analyzed using a commercially available line immunoblot ENA assay (INNO-LIA ANA, Fujirebio, Japan). This kit provides a qualitative in vitro assay for human autoantibodies of the IgG class to 13 different antigens: RNP-70, RNP-A, RNP-C, Ro-52, Ro-60, La/SSB, Scl-70, CENP-B, histones, Jo-1, Sm, P ribosomal protein and U1-nRNP complex in serum or plasma. The overall sensitivity and specificity of autoantibody detection by LIA was similar or higher as compared to combined conventional techniques.<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">18,19</span></a> This immunoblot has 99.6% specificity to anti-La, whereas anti-Ro60 has 98.2%, and anti-Ro52 has 98.3%.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Furthermore the computer system allow us to detect in the immunoassay anti-Ro and/or anti-La positive with negative ANA test, because in patients with high clinical suspicion of an autoimmune disease the immunoblot ENA assay was performed despite a negative ANA test. Finally, only patients with more than one positive serum samples for anti-Ro/SSA or anti-La/SSB were included in the study.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Clinical and laboratory data were obtained by either two trained observers by reviewing clinical charts or a computerized laboratory data base.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Variables</span><p id="par0065" class="elsevierStylePara elsevierViewall">Dependent variables were single or combined positives for anti-Ro52, anti-Ro60 and anti-La antibodies and all possible combinations were characterized as subgroups for further analysis, e.g. anti-Ro52+/anti-Ro60+/anti-La+, anti-Ro52+/anti-Ro60+/anti-La−, anti-Ro52+anti-Ro60−/anti-La+, anti-Ro52+/anti-Ro60−/anti-La−, anti-Ro52−/anti-Ro60+/anti-La+, anti-Ro52−/anti-Ro60+/anti-La−, anti-Ro52−/anti-Ro60−/anti-La+.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Independent variables included demographics (age, gender), clinical (diagnosis, disease characteristics), laboratory (hemoglobin, leukocyte and platelet counts, thyroid hormone levels) or immunologic (complement levels, hypergammaglobulinemia, rheumatoid factor).</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0075" class="elsevierStylePara elsevierViewall">Descriptive statistics were used with frequencies and percentages for qualitative variables and mean, standard deviation, and range for quantitative variables. Clinical associations between different sets of positive combinations against clinical or laboratory variables were analyzed by contingency tables using chi square of Fisher's exact tests. In all cases alpha level was set at 0.01 as an adjustment for multiple comparisons. Strength of association is presented as odds ratio and its 99% confidence intervals. We performed the cluster analysis of variables using average linkage between groups, and using as interval measure, the squared Euclidean distance. Analyses were performed using SPSS 16.0 (SPSS Inc., Chicago, IL).</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0080" class="elsevierStylePara elsevierViewall">A total of 41,102 serum samples were referred to the Department of Immunology for ANA detection. 12,124 samples were positive from 2970 patients. 322 patients with more than one positive serum sample for anti-Ro52 and/or anti-Ro60 and/or anti-La antibodies with titer dilution >160 were included. Females represented 90.4% of the sample. They had an age between 10 and 84, mean 44.4 and standard deviation 15.7 years. Some isolated sera were positive for immunoblot ENA assay with negative ANA test. But the 322 patients showed all or most of their sera positive for ANA test, and the pattern of sera for each patients were virtually identical. No patient was found in our study with more than one sera negative test for IIF.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Main clinical diagnosis in descending order of frequency were: 129 SS (40.06%), 88 of them had a primary disease, 118 SLE (36.6%), 27 undifferentiated connective tissue disease (8.4%), 26 systemic sclerosis (8.1%) (included 9 CREST syndrome), 16 rheumatoid arthritis (4.9%), 11 discoid lupus (3.4%), 7 mixed connective tissue disease (2.2%) and 5 inflammatory myopathy (1.6%). Secundary Sjögren syndrome was found in 41 patients, mainly associated to SLE (30 patients) and rheumatoid arthritis (5 cases).</p><p id="par0090" class="elsevierStylePara elsevierViewall">In relation to immunofluorescence patterns in HEp-2 cells the fine speckled pattern was the most common in 225 cases (69.8%) followed by homogenous pattern in 64 (19.8%), cytoplasmic pattern in 36 (11.1%), coarse speckled pattern in 23 (7.1%), nucleolar in 18 (5.5%) and centromeric in 9 patients (2.8%). We found a mixed pattern in 53 patients, the most prevalent was homogeneus/fine speckled mixed pattern in 11 of them (3.4% of all patients).</p><p id="par0095" class="elsevierStylePara elsevierViewall">Main clinical and laboratory data of patients with positive samples for anti-Ro52 and/or anti-Ro60 and/or anti-La (322 cases) are presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Specificities of different antigens of these patients are depicted in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. We can see that the most frequent positive finding was anti-Ro52 in 269 patients (83.5%), followed by 205 patients with anti-Ro60 (63.7%) and 155 with anti-La (48.1%).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows different associations between combinations of antibodies anti-Ro52/anti-Ro60/anti-La and diagnosis, clinical or laboratory results. <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> shows significant associations of positive test for the presence of circulating antibody anti-Ro52, anti-Ro60 and anti-La. Since a strict significance level selected, some interesting associations were not presented such as the group anti-Ro52+ with cytoplasmic pattern (OR 3.72, 99% CI: 0.9–16, <span class="elsevierStyleItalic">p</span> value 0.04) and the group anti-Ro60+ with subacute cutaneous lupus (SCLE) (OR 7.0, 99% CI: 0.9–55.3, <span class="elsevierStyleItalic">p</span>: 0.023).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">Using cluster analysis, four groups of autoantibodies can be identified. Cluster 1 comprises antibodies against SmB, SmD, RNP,70, RNP-A and RNP-C. Cluster 2 is formed for antibodies against Scl-70, Ribosomal P, Jo1 and centromere. Cluster 3 is formed for antibodies to Ro60 and SSB. Cluster 4 consisted of antibodies against Ro52 (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0110" class="elsevierStylePara elsevierViewall">Rheumatologists have established the importance of clinical and serological findings in classifying many autoimmune diseases. Some concerns have been published on the importance of critical evaluation of specialized tests in clinical care. It seems that ordering many tests could produce multiple laboratory results that must be carefully evaluated in the context of clinical findings.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">17,21</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">In our study we describe the clinical, diagnostic and immunological associations with all several possible combinations of anti-Ro52, anti-Ro60 and anti-La antibodies, found in a large cohort of patients from a single center in Spain for 10 years. A total of 322 patients presented more than one positivity for these antibodies, and the most prevalent disease were SLE and pSS, mainly associated with immunologic profile anti-Ro52+/anti-Ro60+/anti-La− and anti-Ro52+/anti-Ro60+/anti-La+, respectively.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Our strict definition of statistical significance could make that some associations were lost but we are confident that described associations could be more robust. The clinical and practical relevance of these associations could be particularly interesting for isolated anti-Ro52 (anti-Ro52+/anti-Ro60−/anti-La−). This subset of autoantibodies has independent clinical and immunological associations, data confirmed in our cluster analysis.<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">22,23</span></a> Positive isolated anti-Ro52 antibody was associated with systemic sclerosis, especially those with CREST syndrome, and dermatomyositis (OR 11.65, 99% CI: 1.28–105.79, <span class="elsevierStyleItalic">p</span>: 0.018). Other associations were mainly seen with some laboratory findings such as anti-Jo-1 (OR 3.45, 99% CI: 1.12–10.59, <span class="elsevierStyleItalic">p</span>: 0.03), anti-centromere (OR 2.66, 99% CI: 1.04–2.80, <span class="elsevierStyleItalic">p</span>: 0.03) or particular immunofluorescence patterns such as centromeric, cytoplasmic and nucleolar pattern. Moreover, comparing the isolated positive anti-Ro52+ group (anti-Ro52+/anti-Ro60−/anti-La−) with positive triple reactivity (anti-Ro52+/anti-Ro60+/anti-La+) the clinical, laboratory and diagnosis associations found in one group were the opposite in the other one. So, the immunologic subset anti-Ro52+/anti-Ro60+/anti-La+ was positively associated to xerostomia and fine speckled pattern and negatively to systemic sclerosis (OR 0.22, 99% CI: 0.05–1.00, <span class="elsevierStyleItalic">p</span>: 0.026). This highlights the diagnostic clinical value of the combination. In relation to positive test result for the group of anti-Ro60+, mainly associated with anti-La− (anti-Ro52+/anti-Ro60+/anti-La− and anti-Ro52−/anti-Ro60+/anti-La−), was very indicative for SLE.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Our findings are similar to those previously reported.<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6,22–25</span></a> The presence of circulating antibody anti-Ro52, anti-Ro60 and anti-La positive predisposed to xerostomia and xerophthalmia (xerostomia in anti-Ro60 OR 1.75, 99% CI: 1.10–2.79, <span class="elsevierStyleItalic">p</span>: 0.012). This clinical data supported by numerous studies on the pSS.<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6–9,11,17,24</span></a> Positive anti-Ro52 with negative anti-Ro60 and anti-La exhibited negative association with photosensitivity, however in previous studies patients with anti-Ro52+ had higher frequency of cutaneous involvement.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">17,26</span></a> Furthermore, this immunological combination (anti-Ro52+/anti-Ro60−/anti-La−) was also inversely associated with xerostomia and xerophthalmia. However in previous studies isolated positive anti-Ro52 was closely related with the main clinical, histopathological and immunological features of pSS.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a> Isolated positive anti-Ro60 or anti-Ro60+ combined with anti-Ro52+ increased the probability for SLE or overlap SLE/SS, as described in several works,<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">11,17,28</span></a> but also in our cohort was strongly associated to oral ulcers and arthritis. Anti-La reactivity was strongly associated to pSS and its main clinical manifestations (xerostomia and xerophthalmia), as in many others studies in different populations.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">11,17,26</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Most previous research studies on the usefulness of these antibodies have been performed on samples from patients with a diagnosed autoimmune disease, especially SLE and SS. However there are few studies performed to describe the diagnostic association of anti-Ro and anti-La antibodies identified in a consecutive samples.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">In addition to diagnosis, we determined the utility of the immunologic profiles with anti-Ro52 and/or anti-Ro60 and/or anti-La in the prediction of clinical and laboratory data in a consecutive sample of patients and these are ordered for all departments of hospital and primary care. We reviewed all the samples of each patient during this period and registered the more prevalent anti-Ro52, anti-Ro60 and anti-La reactivity combination. The selected positivity cut-off point >160 increases the validity of the study, due to the positive ANA test and anti-Ro/SSA and anti-La/SSB assay can be detected in up to 25–30% and 1.6% of healthy individuals, respectively. Their prevalence is higher with age, and its positivity without a relevant clinical data can be misleading.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Therefore, in our study we showed an immune profile may lead us to a certain diagnosis or development of disease manifestations. This is more important in the onset of autoimmune diseases, due to circulating antibodies may be present several years before disease diagnosis, and could indicate the severity of its manifestations.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">17,30</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Some limitations inherent to these studies are the retrospective clinical evaluations of clinical charts and the possible diagnostic biases in treating physicians who see these patients and order specialized laboratory tests. Many of our patients with positive ANA test resulted negative for the immunoblot ENA assay determination. This could be related to the type of immunoassay developed. In cases with a high clinical suspicion specific antibody detection is recommended.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Ethical disclosures</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Protection of human and animal subjects</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare that this research has not been conducted experiments on humans or animals.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Confidentiality of data</span><p id="par0155" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of the workplace on the publication of patient data.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Right to privacy and informed consent</span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors declare that this article does not appear patient data.</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflict of interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres823634" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec820297" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres823633" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec820298" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Research center" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Samples" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Variables" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 8 => array:3 [ "identificador" => "sec0045" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0065" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-04-28" "fechaAceptado" => "2015-10-30" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec820297" "palabras" => array:4 [ 0 => "Anti-Ro/SS-A antibodies" 1 => "Anti-La/SS-B antibodies" 2 => "Autoimmune disease" 3 => "Immunofluorescence patterns" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec820298" "palabras" => array:4 [ 0 => "Anticuerpo anti-Ro/SSA" 1 => "Anticuerpo anti-La/SSB" 2 => "Enfermedades autoinmunes" 3 => "Patrones de inmunofluorescencia indirecta" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Several antibodies have proven to be useful in autoimmune diseases, as markers for diagnosis, prognosis or clinical manifestations. Our objective was to evaluate the diagnosis and manifestations associated for antibodies anti-Ro52, anti-Ro60 and anti-La at a referral hospital in Spain.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We retrospectively analyzed the antigenic specificities of the consecutive samples submitted to the Immunology Unit for antinuclear antibody screening between 2002 and 2012. We included patients with more than one positive sample for some of the autoantibodies anti-Ro52, anti-Ro60 or anti-La. We also reviewed diagnosis, clinical and laboratory features. As dependent variable we evaluated possible combinations of anti-Ro52, anti-Ro60 and anti-La.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">322 patients, 91% females, were studied (age 44.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15.51 years). The most frequent diagnosis was Sjögren's syndrome (40.06%) and systemic lupus erythematosus (SLE) (36.6%). The most prevalent pattern by indirect immunofluorescence was the fine speckled (69.9%). Anti-Ro52+/anti-Ro60+/anti-La+ combination was positively associated with fine speckled pattern (<span class="elsevierStyleItalic">p</span>: 0.001) and negatively with homogeneous (<span class="elsevierStyleItalic">p</span>: 0.016) and cytoplasmic pattern (<span class="elsevierStyleItalic">p</span>: 0.002). Isolated anti-Ro52+ was negatively associated with fine speckled pattern (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001) and positively with the cytoplasmic one (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001). The main positive associations with clinical symptoms were xerostomia and xerophthalmia with anti-Ro52+/anti-Ro60+/anti-La+ (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001), oral ulcers with anti-Ro52+/anti-Ro60+/anti-La− (<span class="elsevierStyleItalic">p</span>: 0.002) and alopecia with anti-Ro52−/anti-Ro60+/anti-La− (<span class="elsevierStyleItalic">p</span>: 0.003). Negative associations were xerophthalmia and photosensitivity with anti-Ro52+/anti-Ro60−/anti-La− (<span class="elsevierStyleItalic">p</span>: 0.003). Laboratory positive associations were hypergammaglobulinemia with anti-Ro52+/anti-Ro60+/anti-La+ (<span class="elsevierStyleItalic">p</span>: 0.003), and hypocomplementemia with anti-Ro52−/anti-Ro60+/anti-La− (<span class="elsevierStyleItalic">p</span>: 0.003). Leucopenia was negatively associated with anti-Ro52+/anti-Ro60−/anti-La− (<span class="elsevierStyleItalic">p</span>: 0.003).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Our study found significant relationships between clinical and laboratory manifestations with different patterns of antibodies to anti-Ro52, anti-Ro60 and anti-La. The combination of antibodies might be clinically useful due to prognostic and therapeutic implications.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Varios anticuerpos han demostrado ser útiles en enfermedades autoinmunes, como marcadores de diagnóstico, pronóstico o manifestaciones clínicas. Nuestro objetivo fue evaluar el diagnóstico y las manifestaciones asociadas a anticuerpos anti-Ro52, anti-Ro60 y anti-La en un hospital de referencia en España.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se analizaron retrospectivamente las especificidades antigénicas de todas las muestras consecutivas solicitadas a la Unidad de Inmunología para la detección de anticuerpos antinucleares entre 2002 y 2012. Se incluyeron pacientes con más de una muestra positiva para algunos de los autoanticuerpos anti-Ro52, anti-Ro60 o anti-La, y se revisaron sus características diagnósticas, clínicas y de laboratorio. Como variable dependiente se evaluaron las combinaciones de anti-Ro52, anti-Ro60 y anti-La.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">322 pacientes, 91% mujeres, fueron estudiados (edad 44.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15.51 años). El diagnóstico más frecuente fue el síndrome de Sjögren (40.06%), y el lupus eritematoso sistémico (LES) (36.6%). El patrón por inmunofluorescencia indirecta más prevalente fue el moteado fino (69.9%). La combinación Anti-Ro52+/anti-Ro60+/anti-La+ se asoció positivamente con el patrón moteado fino (p: 0.001) y negativamente con el homogéneo (p: 0.016) y el citoplasmático (p: 0.002). Anti-Ro52+ aislado se asoció negativamente con el patrón moteado fino (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001) y positivamente con el citoplasmático (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001). La principal asociación con síntomas clínicos fue de xerostomía y xeroftalmia con anti-Ro52+/anti-Ro60+/anti-La+ (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001), úlceras orales con anti-Ro52+/anti-Ro60+/anti-La− (p: 0.002) y alopecia con anti-Ro52−/anti-Ro60+/anti-La−. Asociaciones negativas fueron xeroftalmia y fotosensibilidad con anti-Ro52+/anti-Ro60−/anti-La− (p: 0.003). Asociaciones positivas de laboratorio fueron hipergammaglobulinemia con anti-Ro52+/anti-Ro60+/anti-La+ (p: 0.003) e hipocomplementemia con anti-Ro52−/anti-Ro60+/anti-La− (p: 0.003). Leucopenia se asoció negativamente con anti-Ro52+/anti-Ro60−/anti-La− (p: 0.003).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusión</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Nuestro estudio encontró una relación significativa entre las manifestaciones clínicas y de laboratorio con diferentes patrones de anticuerpos anti-Ro52, anti-Ro60 y anti-La. La combinación de anticuerpos podría ser clínicamente útil, debido a implicaciones pronósticas y terapéuticas.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1720 "Ancho" => 2651 "Tamanyo" => 147282 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Cluster analysis to identify cluster of antibodies in our sample of patients.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Frequency (%)/(<span class="elsevierStyleItalic">n</span>) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="char" valign="top"><span class="elsevierStyleItalic">Clinical features</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Xerostomia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45.3 (146) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Xerophthalmia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48.8 (157) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Arthritis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41 (132) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Raynaud's phenomenon \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27.6 (89) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Photosensitivity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27 (87) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Oral ulcers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24.2 (78) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Alopecia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18.3 (59) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Interstitial pneumonitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.6 (34) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Acute cutaneous lupus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.6 (34) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Peripheral nervous system involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.3 (30) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Vasculitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.5 (24) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Glomerulonephritis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.5 (21) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Central nervous system involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.5 (21) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pleural effusion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.9 (19) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pericardial effusion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.6 (18) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Discoid lupus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.3 (17) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Subacute cutaneous lupus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (13) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Heart blockade \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.6 (2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Laboratory features</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Rheumatoid factor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43.5 (140) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Leukopenia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37.3 (120) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lymphopenia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32.3 (104) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hypergammaglobulinemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26.1 (84) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Anemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25.2 (81) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hypocomplementemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24.5 (79) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hypothyroidism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.5 (37) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Thrombocytopenia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.9 (35) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1384884.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Main clinical and laboratory data of patients with positive samples for anti-Ro52 and/or anti-Ro60 and/or anti-La (322 cases).</p>" ] ] 2 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">INNOLIA-updated \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Frequency (%)/(<span class="elsevierStyleItalic">n</span>) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ro52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">83.5 (269) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ro60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">63.7 (205) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">La \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48.1 (155) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">RNPA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.0 (29) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">RNPC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.1 (23) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SmB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.5 (21) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Centromere \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.9 (19) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SmD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.0 (16) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">RNP70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.7 (15) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Jo-1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.0 (13) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ribosomal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.8 (9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Scl-70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.6 (5) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1384883.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Specificities of different antigens of patients with positive samples for anti-Ro52 and/or anti-Ro60 and/or anti-La (322 cases).</p>" ] ] 3 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">SLE, systemic lupus erythematosus.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Anti-Ro/SSA and/or anti-La/SSB immunoblot ENA assay<br>Frequency %/(<span class="elsevierStyleItalic">n</span>) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Association \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">99% Confidence interval</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="9" align="left" valign="top">Anti-Ro52+/anti-Ro60+/anti-La+<br>36.3% (117)</td><td class="td" title="table-entry " align="char" valign="top">Fine speckled pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.96 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Xerostomia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Primary Sjögren \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.79 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Xerophthalmia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.62 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Rheumatoid factor + \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.46 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Hypergammaglobulinemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.56 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Homogeneous pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.002 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.75 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Cytoplasmic pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.002 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.68 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Systemic sclerosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.004 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.73 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Anti-Ro52+/anti-Ro60+/anti-La−<br>17.0% (55)</td><td class="td" title="table-entry " align="char" valign="top">Oral ulcers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.002 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.80 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Arthritis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.006 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.03 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.009 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.84 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anti-Ro52+/anti-Ro60−/anti-La+<br>4.3% (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">Rheumatoid factor + \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18.19 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="11" align="left" valign="top">Anti-Ro52+/anti-Ro60−/anti-La−<br>26.7% (86)</td><td class="td" title="table-entry " align="char" valign="top">Systemic sclerosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30.72 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Nucleolar pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36.59 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">CREST \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.002 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51.82 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Cytoplasmic pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.63 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Centromeric pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.04 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Xerophthalmia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.78 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Leukopenia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.78 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Photosensitivity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.76 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Rheumatoid factor + \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.67 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.56 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Fine speckled pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.45 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="5" align="left" valign="top">Anti-Ro52−/anti-Ro60+/anti-La−<br>7.4% (24)</td><td class="td" title="table-entry " align="char" valign="top">Anti-RNP C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.78 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21.48 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Anti-RNP 70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.002 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25.97 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Alopecia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.41 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Hypocomplementemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.94 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Oral ulcers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.009 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.48 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anti-Ro52−/anti-Ro60−/anti-La+<br>4.0% (13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">No association found for <span class="elsevierStyleItalic">p</span> value<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1384885.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Associations between combinations of anti-Ro52, anti-Ro60 and anti-La antibodies and diagnosis, clinical or laboratory results.</p>" ] ] 4 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">SLE, systemic lupus erythematosus.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Anti-Ro/SSA and/or anti-La/SSB immunoblot ENA assay \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Association \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">99% Confidence interval</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Anti-Ro52+</td><td class="td" title="table-entry " align="char" valign="top">Xerostomia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.92 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Xerophthalmia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.002 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.79 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Anti-RNP C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.43 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="8" align="left" valign="top">Anti-Ro60+</td><td class="td" title="table-entry " align="char" valign="top">Anti-La \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.27 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.55 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Fine speckled pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.25 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Undifferentiated connective tissue \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.002 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17.11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Xerophthalmia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.004 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.06 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Cytoplasmic pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.50 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Systemic sclerosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.37 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Nucleolar pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.44 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="15" align="left" valign="top">Anti-La+</td><td class="td" title="table-entry " align="char" valign="top">Anti-Ro60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.27 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Fine speckled pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.08 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.06 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Rheumatoid factor+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.09 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Hypergammaglobulinemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.12 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Primary Sjögren \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.95 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Xerostomia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.44 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Xerophthalmia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.39 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Cytoplasmic pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.53 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Systemic sclerosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.37 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Anti-RNP 70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.54 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Oral ulcers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.005 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.82 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Anti-RNP A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.005 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.74 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Nucleolar pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.005 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.71 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Anti-RNP C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.007 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.76 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Homogeneous pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.009 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.86 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1384886.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Associations between presence of circulating anti-Ro52+, anti-Ro60+ and anti-La+ antibodies and clinical and laboratory data.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0155" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autoantibodies as 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 19 | 14 | 33 |
| 2024 October | 108 | 43 | 151 |
| 2024 September | 84 | 35 | 119 |
| 2024 August | 131 | 71 | 202 |
| 2024 July | 118 | 49 | 167 |
| 2024 June | 142 | 61 | 203 |
| 2024 May | 149 | 53 | 202 |
| 2024 April | 104 | 26 | 130 |
| 2024 March | 100 | 52 | 152 |
| 2024 February | 93 | 31 | 124 |
| 2024 January | 72 | 36 | 108 |
| 2023 December | 85 | 38 | 123 |
| 2023 November | 79 | 53 | 132 |
| 2023 October | 106 | 50 | 156 |
| 2023 September | 143 | 49 | 192 |
| 2023 August | 67 | 19 | 86 |
| 2023 July | 100 | 38 | 138 |
| 2023 June | 84 | 30 | 114 |
| 2023 May | 114 | 29 | 143 |
| 2023 April | 111 | 17 | 128 |
| 2023 March | 445 | 70 | 515 |
| 2023 February | 143 | 33 | 176 |
| 2023 January | 104 | 24 | 128 |
| 2022 December | 164 | 42 | 206 |
| 2022 November | 112 | 45 | 157 |
| 2022 October | 144 | 31 | 175 |
| 2022 September | 89 | 30 | 119 |
| 2022 August | 95 | 44 | 139 |
| 2022 July | 88 | 36 | 124 |
| 2022 June | 76 | 31 | 107 |
| 2022 May | 125 | 72 | 197 |
| 2022 April | 130 | 43 | 173 |
| 2022 March | 139 | 51 | 190 |
| 2022 February | 123 | 32 | 155 |
| 2022 January | 79 | 38 | 117 |
| 2021 December | 51 | 46 | 97 |
| 2021 November | 45 | 52 | 97 |
| 2021 October | 48 | 51 | 99 |
| 2021 September | 43 | 41 | 84 |
| 2021 August | 41 | 54 | 95 |
| 2021 July | 29 | 44 | 73 |
| 2021 June | 45 | 55 | 100 |
| 2021 May | 51 | 70 | 121 |
| 2021 April | 76 | 94 | 170 |
| 2021 March | 61 | 40 | 101 |
| 2021 February | 45 | 39 | 84 |
| 2021 January | 40 | 30 | 70 |
| 2020 December | 39 | 34 | 73 |
| 2020 November | 29 | 25 | 54 |
| 2020 October | 16 | 20 | 36 |
| 2020 September | 24 | 22 | 46 |
| 2020 August | 31 | 27 | 58 |
| 2020 July | 29 | 20 | 49 |
| 2020 June | 29 | 24 | 53 |
| 2020 May | 28 | 25 | 53 |
| 2020 April | 38 | 26 | 64 |
| 2020 March | 15 | 4 | 19 |
| 2020 February | 2 | 0 | 2 |
| 2019 May | 1 | 2 | 3 |
| 2018 December | 1 | 0 | 1 |
| 2018 May | 3 | 1 | 4 |
| 2018 April | 34 | 12 | 46 |
| 2018 March | 30 | 9 | 39 |
| 2018 February | 25 | 6 | 31 |
| 2018 January | 9 | 5 | 14 |
| 2017 December | 13 | 14 | 27 |
| 2017 November | 23 | 12 | 35 |
| 2017 October | 24 | 19 | 43 |
| 2017 September | 28 | 21 | 49 |
| 2017 August | 32 | 20 | 52 |
| 2017 July | 30 | 16 | 46 |
| 2017 June | 37 | 37 | 74 |
| 2017 May | 44 | 22 | 66 |
| 2017 April | 35 | 37 | 72 |
| 2017 March | 43 | 34 | 77 |
| 2017 February | 7 | 24 | 31 |
| 2017 January | 23 | 23 | 46 |
| 2016 December | 36 | 20 | 56 |
| 2016 November | 31 | 24 | 55 |
| 2016 October | 66 | 44 | 110 |
| 2016 September | 59 | 17 | 76 |
| 2016 August | 7 | 1 | 8 |
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