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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Beh&#231;et&#39;s disease is a chronic autoinflammatory disease characterized by recurrent attacks&#46; Although the precise role is unknown&#44; certain changes that occur in immune system homeostasis are believed to play a role&#44; and there may be an increased tendency for autoimmunity although this is arguable&#46; Various studies carried out until now have suggested that antinuclear antibody screening tests&#44; which provide guidance for the diagnosis of autoimmune diseases&#44; do not point to a significant positivity in these patients&#46; However&#44; certain specific and nonspecific staining patterns or cell organelle staining associated with certain diseases have been identified in ANA screenings in recent years&#46; The aim of this study was to reveal these patterns in more detail and to investigate whether they could be related&#44; even to a minor extent&#44; to the yet unexplained etiopathogenesis of the disease&#46; With this in mind&#44; we aimed to investigate autoantibodies in active and inactive period Beh&#231;et&#39;s patients in this study&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Materials and method</span><p id="par0010" class="elsevierStylePara elsevierViewall">140 patients &#40;87 females&#44; 53 males&#41; with an average of 41&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3 years who were being followed up for Beh&#231;et&#39;s Disease&#44; and a control group consisting of a total of 736 &#40;464 females&#44; 272 males&#41; healthy volunteers made up of blood donors without any disease whose average age was 50&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4 years were included in the study&#46; In compliance with international criteria&#44; patients with signs and symptoms of oral or genital aphthae&#44; pathergy positivity&#44; etc&#46; were regarded as active&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;2</span></a> According to this&#44; 33 patients who were being followed up for oral aphthae but had not been diagnosed with Beh&#231;et&#39;s Disease&#46; After the study&#44; it was confirmed that these patients were diagnosed with Beh&#231;et&#46; The remaining 107 patients had Beh&#231;et&#39;s Disease&#46; Peripheral venous blood was collected from the patients and the sera were separated&#46; The sera were left to wait at &#8722;20<span class="elsevierStyleHsp" style=""></span>&#176;C for indirect immunofluorescence antibody testing &#40;IFA&#41;&#46; 1&#47;40 and 1&#47;100 dilution were done for the sera to be studied&#46; Dilutions of 1&#47;100 and above were regarded as positive&#46; HEp-2 IIF tests from the company EUROIMMUN &#40;IIFT Mosaic&#58; HEp-20-10&#47;Liver Monkey Germany Lot&#58; F111125DG&#41; were prepared in accordance with the recommended procedure&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">3</span></a> All the slides were examined by same researcher under a fluorescent microscope &#40;Zeiss-Eurostar&#44; Germany&#41; at 20x and 40x magnifications&#46; Positivities were classified according to fluorescence intensity and nuclear and cytoplasmic stainings were examined&#46; Where necessary&#44; dilutions were made&#44; and the test was repeated and positivities were graded&#46; Because the number of subjects in certain cells was less than five in the data frame&#44; the Fisher-Freeman-Halton Exact Test&#44; which is Fisher&#39;s Exact Test generalized for RXC tables&#44; was used&#46; Comparison of the data was done using the SPSS 11&#46;0 statistics software on a computer&#46; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was used as the significance interval&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0015" class="elsevierStylePara elsevierViewall">An ANA positivity rate of 8&#46;3&#37; was found in the total of 736 healthy controls we studied&#46; ANA patterns observed in healthy controls&#59; 7 cases &#40;1&#37;&#41; Homogeneous pattern&#44; 17 cases &#40;2&#46;3&#37;&#41; Spotted pattern&#44; 15 cases &#40;2&#37;&#41; Nucleolar pattern&#44; 5 cases &#40;0&#46;6&#37;&#41; DFS-70 pattern&#44; 1 case &#40;0&#46;1&#37;&#41; Sentriol pattern&#44; 1 case &#40;0&#46;1&#37;&#41; Sentromer pattern&#44; 5 cases &#40;0&#46;7&#37;&#41; Midbody pattern&#46; This rate was 10&#46;7&#37; in 107 Beh&#231;et&#39;s patients&#46; ANA patterns in patients with Beh&#231;et&#39;s diagnosis&#59; 1 case &#40;0&#46;7&#37;&#41; Spotted pattern&#44; 1 case &#40;0&#46;7&#37;&#41; Nucleolar pattern&#44; 3 cases &#40;2&#37;&#41; DFS-70 pattern&#44; 2 cases &#40;1&#46;9&#37;&#41; Sentriol pattern&#44; 3 cases &#40;2&#37;&#44; 9&#41; Midbody pattern&#46; It was rate 9&#46;09&#37; in 33 patients who were followed up with oral aphthae and later diagnosed as Beh&#231;et&#46; ANA patterns in patients with oral aphthae&#59; 1 case &#40;3&#37;&#41; DFS-70 pattern&#44; 1 case &#40;3&#46;03&#37;&#41; Midbody pattern&#46; There was no significant difference between the groups in terms of autoantibody positivity &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; When observed in terms of staining patterns&#44; there was no difference between the controls and Beh&#231;et&#39;s patients &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0020" class="elsevierStylePara elsevierViewall">Beh&#231;et&#39;s Disease is defined as a typical systemic vasculitic disease accompanied by recurrent oral and genital ulcers and uveitis&#46; However&#44; the etiopathogenesis of the disease is uncertain&#46; Genetic predisposition and environmental factors are usually blamed&#46; An autoimmunity process by abnormal T and B cell reactions and autoantigens is being focused on&#46; While inflammation in which Th1 type cytokine response and neutrophils play a role is detected in Beh&#231;et&#39;s Disease&#44; the hallmarks are no indication of the classic autoimmune disease&#44; such as predominance of the female sex and autoantibody positivity&#46; B cell numbers are normal but overall B cell activation is increased&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">4</span></a> However&#44; no autoantibody tests or specific autoantigen have been identified in patients&#46; The anti-endothelial cell antibody has been identified and alpha-enolase has been reported to be a possible antigen&#46; In addition&#44; kinetin&#44; which is an endoplasmic reticulum-dependent integral membrane protein&#44; has been reported as a possible autoantigen in Beh&#231;et&#39;s Disease&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Antinuclear antibodies &#40;ANA&#41; can be detected in several autoimmune diseases&#44; such as SLE &#40;Systemic Lupus Erythematosus&#41;&#44; Scleroderma&#44; and Sjogren&#39;s Syndrome in particular&#44; and lead to a diagnosis&#46; ANA tests can assist diagnosis by detecting antibodies that target various proteins found in the cell structure and proteins&#44; receptors&#44; and enzymes associated with mitosis as well as the cell nucleus&#46; While the increased tendency for autoimmunity in Beh&#231;et&#39;s Disease has led researchers to the detection of autoantibodies&#44; the presence of a specific autoantibody associated with Beh&#231;et&#39;s Disease has not been reported until now&#46; In one study&#44; it is stated that ANA prevalence was found high among Beh&#231;et&#39;s patients&#44; that a significant increase was observed compared to the control group&#44; and that this can be linked to polyclonal B cell activation&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">6</span></a> In the study by Chun et al&#46;&#44; it is reported that the rate of patients in whom ANA positivity was detected in a series of 554 cases was 8&#46;3&#37;&#44; but it is emphasized that the results are not related to the severity of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">7</span></a> In our series&#44; the rate of ANA-positive patients was 10&#46;7&#37;&#46; When the staining patterns of these patients are examined&#44; nonspecific patterns other than the homogenous&#44; speckle-type patterns observed frequently in autoimmune rheumatic diseases&#44; while few in numbers&#44; stand out&#46; Detected patterns include midbody&#44; centriole&#44; nucleolar&#44; and speckled staining and anti-DFS70 &#40;Anti-dense fine speckles 70&#41; staining&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In midbody staining&#44; intercellular bridge-like staining occurs in cells in anaphase or telophase&#46; In cells in metaphase&#44; granular staining in the chromosomal region can be noticed&#46; Until now&#44; it has not been associated with a specific autoimmune disease&#46; Autoantibody positivity is commonly found in low titers in healthy individuals and in diseases other than rheumatic diseases&#46; However&#44; such autoantibody positivity can sometimes also be a prodrome of a rheumatic disease that may be detected in the future&#46; Centrioles are at the center of the net-like structure &#40;spindle&#41; which is formed by microtubule and observed in mitosis&#46; Anti-centriole antibodies have been rarely detected in scleroderma spectrum diseases&#44; systemic sclerosis and Raynaud&#39;s phenomenon&#46; Hayakawa et al&#46; have reported finding them in a patient with systemic sclerosis and pulmonary hypertension&#46; In conclusion&#44; they report that mitosis-related antigens like centrioles can be associated with vascular damage&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">8</span></a> It is noteworthy that this pattern&#44; which was not detected in the healthy controls&#44; was detected in Beh&#231;et&#39;s patients in our series&#44; and that the disease&#44; in essence&#44; is a form of vasculitis&#46; Nucleolar staining and speckled staining&#44; on the other hand&#44; are usually detected in mixed connective tissue diseases such as scleroderma&#44; polymyositis&#44; rheumatoid arthritis&#44; and systemic lupus&#44; and have no known association with Beh&#231;et&#39;s Disease&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Anti DFS70 was first identified by Ochs et al&#46; in 1994 in the form of a thin speckled staining in HEp-2 cells and a positive reaction in the chromosomal region in mitotic cells and was given this name because it formed a band of about 70<span class="elsevierStyleHsp" style=""></span>kDa when immunoblotting was done&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">9</span></a> The target antigen of anti-DFS70 is identified as Lens Epithelium-Derived Growth Factor &#40;LEDGF&#47;p75&#41; and as transcription coactivator p75&#46; The antigen targeted by this antibody has important biological functions&#44; such as sustaining cell life and increasing the cell&#39;s resistance to cellular stress&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">10</span></a> The anti-DFS70 antibody can be detected in a variety of chronic inflammatory conditions&#44; in cancer patients&#44; and in a significant portion of the healthy population&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">11&#44;12</span></a> Beh&#231;et&#39;s Disease&#44; which forms the basis of our study group&#44; is an autoinflammatory disease as it is well known and anti-DFS70 positivity was found at a rate of 2&#46;1&#37; in our series of Beh&#231;et&#39;s patients and at a rate of 0&#46;7&#37; in the healthy controls&#44; and interestingly&#44; all of these patients were female&#46; In Japan&#44; DFS70 is reported at a rate of approximately 10&#37; among healthy people&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">11</span></a> but in our series&#44; this rate is much lower than in Japanese society&#46; The recognition of a DFS70 pattern in ANA testing is very important&#46; DFS70 can be found alongside anti-p80 coilin antibodies or SS-A positivity in rheumatoid diseases&#46; In their study on patients with Vogt-Koyanagi-Harada &#40;VKH&#41; Disease and Beh&#231;et&#39;s patients with panuveitis&#44; Yamada et al&#46; investigated LEDGF and found the anti lgG and anti-LEDGF detection rate as 66&#46;7&#37; in this group&#44; as 21&#46;6&#37; in healthy controls&#44; as 34&#37; in Beh&#231;et&#39;s patients with panuveitis&#44; and as 25&#46;0&#37; in sarcoidosis patients&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">13</span></a> LEDGF is a protein linked to the stress reaction and for this reason&#44; can increase in inflammatory lesions and break immune tolerance&#44; but the fact that it can be detected in healthy controls decreases the likelihood of its direct association with the disease&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The inflammatory process in Beh&#231;et&#39;s patients may trigger DFS70 positivity&#44; and centriole staining may be associated with vasculitis&#46; However&#44; our results also support the general belief that there is no highly specific autoantibody associated with Beh&#231;et&#39;s disease&#46; It is noteworthy&#44; however&#44; that ANA staining patterns&#44; the exact disease associations of which have not yet been revealed&#44; can be found more in these patients&#44; considering that chronic inflammatory reactions can lead to the breakdown of immune tolerance&#46; The treatment of the disease with immunosuppressants is related to the ability to suppress with these treatments the inflammation that occurs due to immune response and endothelial dysfunction&#46; There are still many unanswered questions regarding the pathogenesis of the disease&#46; The detection of nonspecific patterns in our results suggests an indirect relationship with the disease&#44; and the unknowns should continue to be investigated&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflict of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The autoinflammatory character of Beh&#231;et&#39;s Disease has led researchers to investigate the role of autoantibodies&#46; However&#44; no significant positive result has been reported for autoantibody tests for the disease&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Aims</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To investigate the specific and nonspecific staining patterns of Beh&#231;et&#39;s Disease &#40;BD&#41; patients&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">140 patients &#40;87 females&#44; 53 males&#41; with an average of 41&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3 years who were being followed up for Beh&#231;et&#39;s Disease&#44; and a control group consisting of a total of 736 &#40;464 females&#44; 272 males&#41; healthy volunteers made up of blood donors without any disease whose average age was 50&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4 years were included in the study&#46; Peripheral venous blood was collected from the patients and the sera were separated&#46; Patient sera were studied by indirect immunofluorescence antibody test &#40;IFA&#41; at a dilution of 1&#47;40 and 1&#47;100&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A total of 140 &#40;87 females&#44; 53 males&#41; Beh&#231;et&#39;s Disease patients and 736 &#40;464 females&#44; 272 males&#41; healthy controls were examined&#46; The rate of ANA positivity was 11&#46;6&#37; in the control group and 10&#46;7&#37; in the Beh&#231;et&#39;s Disease group&#46; In general&#44; no difference was detected between the patients and the healthy controls in terms of autoantibody positivity &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; However&#44; when examined in terms of patterns&#44; the low detection of DFS70 and the observation of centriole staining type patterns in Beh&#231;et&#39;s Disease patients was noteworthy &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Autoantibody tests&#44; which hold an important place in classic autoimmune diseases&#44; are not necessary for Beh&#231;et&#39;s patients&#44; but they should be examined in terms of nonspecific patterns&#46;</p></span>"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Antecedentes</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El car&#225;cter autoinflamatorio de la enfermedad de Beh&#231;et &#40;EB&#41; ha llevado a los investigadores a estudiar el rol de los autoanticuerpos&#46; Sin embargo&#44; no se ha reportado un resultado positivo significativo para las pruebas de autoanticuerpos&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Investigar los patrones de tinci&#243;n espec&#237;ficos y no espec&#237;ficos de los pacientes con EB&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se incluy&#243; en el estudio a 140 pacientes &#40;87 mujeres y 53 varones&#41; con una edad media de 41&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3 a&#241;os con seguimiento por EB&#44; y un grupo control que incluy&#243; a un total de 736 voluntarios sanos &#40;464 mujeres y 272 varones&#41; integrados por donantes de sangre sin enfermedad alguna&#44; con una edad media de 50&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4 a&#241;os&#46; Se extrajo sangre de vena perif&#233;rica a todos los pacientes&#44; separ&#225;ndose el suero&#44; que se estudi&#243; mediante el test de anticuerpos por inmunofluorescencia directa &#40;IFA&#41; a un factor de diluci&#243;n de 1&#47;40 y 1&#47;100&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se examin&#243; a un total de 140 pacientes &#40;87 mujeres y 53 varones&#41; con EB y 736 controles sanos &#40;464 mujeres y 272 varones&#41;&#46; La tasa de positividad de ANA fue del 11&#44;6&#37; en el grupo control y del 10&#44;7&#37; en el grupo de EB&#46; En general no se detect&#243; diferencia entre los pacientes y los controles sanos en t&#233;rminos de positividad de autoanticuerpos &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46; Sin embargo&#44; al realizarse el examen en t&#233;rminos de patrones&#44; fue destacable la baja detecci&#243;n de DFS70 y la observaci&#243;n de los patrones tipo tinci&#243;n de centriolos en los pacientes con EB &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusi&#243;n</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Los test de autoanticuerpos&#44; que ocupan una posici&#243;n importante en las enfermedades autoinmunes cl&#225;sicas&#44; no son necesarios para los pacientes con EB&#44; aunque deber&#237;an examinarse en t&#233;rminos de patrones no espec&#237;ficos&#46;</p></span>"
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Original Article
Are the specific and nonspecific ANA staining patterns of Behçet's Disease patients important?
¿Son importantes los patrones de tinción ANA específicos y no específicos para los pacientes con enfermedad de Behçet?
Fulya Ilhana, Rahime Aksoyb,
Corresponding author
rahimeaksoy77@yahoo.com

Corresponding author.
, Hüseyin Tutkakc
a Department of Immunology, Faculty of Medicine, Elazığ University, Elaziğ, Turkey
b Department of Hematology, Faculty of Medicine, Ankara University, Ankara, Turkey
c Department of Immunology and Allergy Diseases, Faculty of Medicine, Ankara University, Ankara, Turkey
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Beh&#231;et&#39;s disease is a chronic autoinflammatory disease characterized by recurrent attacks&#46; Although the precise role is unknown&#44; certain changes that occur in immune system homeostasis are believed to play a role&#44; and there may be an increased tendency for autoimmunity although this is arguable&#46; Various studies carried out until now have suggested that antinuclear antibody screening tests&#44; which provide guidance for the diagnosis of autoimmune diseases&#44; do not point to a significant positivity in these patients&#46; However&#44; certain specific and nonspecific staining patterns or cell organelle staining associated with certain diseases have been identified in ANA screenings in recent years&#46; The aim of this study was to reveal these patterns in more detail and to investigate whether they could be related&#44; even to a minor extent&#44; to the yet unexplained etiopathogenesis of the disease&#46; With this in mind&#44; we aimed to investigate autoantibodies in active and inactive period Beh&#231;et&#39;s patients in this study&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Materials and method</span><p id="par0010" class="elsevierStylePara elsevierViewall">140 patients &#40;87 females&#44; 53 males&#41; with an average of 41&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3 years who were being followed up for Beh&#231;et&#39;s Disease&#44; and a control group consisting of a total of 736 &#40;464 females&#44; 272 males&#41; healthy volunteers made up of blood donors without any disease whose average age was 50&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4 years were included in the study&#46; In compliance with international criteria&#44; patients with signs and symptoms of oral or genital aphthae&#44; pathergy positivity&#44; etc&#46; were regarded as active&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;2</span></a> According to this&#44; 33 patients who were being followed up for oral aphthae but had not been diagnosed with Beh&#231;et&#39;s Disease&#46; After the study&#44; it was confirmed that these patients were diagnosed with Beh&#231;et&#46; The remaining 107 patients had Beh&#231;et&#39;s Disease&#46; Peripheral venous blood was collected from the patients and the sera were separated&#46; The sera were left to wait at &#8722;20<span class="elsevierStyleHsp" style=""></span>&#176;C for indirect immunofluorescence antibody testing &#40;IFA&#41;&#46; 1&#47;40 and 1&#47;100 dilution were done for the sera to be studied&#46; Dilutions of 1&#47;100 and above were regarded as positive&#46; HEp-2 IIF tests from the company EUROIMMUN &#40;IIFT Mosaic&#58; HEp-20-10&#47;Liver Monkey Germany Lot&#58; F111125DG&#41; were prepared in accordance with the recommended procedure&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">3</span></a> All the slides were examined by same researcher under a fluorescent microscope &#40;Zeiss-Eurostar&#44; Germany&#41; at 20x and 40x magnifications&#46; Positivities were classified according to fluorescence intensity and nuclear and cytoplasmic stainings were examined&#46; Where necessary&#44; dilutions were made&#44; and the test was repeated and positivities were graded&#46; Because the number of subjects in certain cells was less than five in the data frame&#44; the Fisher-Freeman-Halton Exact Test&#44; which is Fisher&#39;s Exact Test generalized for RXC tables&#44; was used&#46; Comparison of the data was done using the SPSS 11&#46;0 statistics software on a computer&#46; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was used as the significance interval&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0015" class="elsevierStylePara elsevierViewall">An ANA positivity rate of 8&#46;3&#37; was found in the total of 736 healthy controls we studied&#46; ANA patterns observed in healthy controls&#59; 7 cases &#40;1&#37;&#41; Homogeneous pattern&#44; 17 cases &#40;2&#46;3&#37;&#41; Spotted pattern&#44; 15 cases &#40;2&#37;&#41; Nucleolar pattern&#44; 5 cases &#40;0&#46;6&#37;&#41; DFS-70 pattern&#44; 1 case &#40;0&#46;1&#37;&#41; Sentriol pattern&#44; 1 case &#40;0&#46;1&#37;&#41; Sentromer pattern&#44; 5 cases &#40;0&#46;7&#37;&#41; Midbody pattern&#46; This rate was 10&#46;7&#37; in 107 Beh&#231;et&#39;s patients&#46; ANA patterns in patients with Beh&#231;et&#39;s diagnosis&#59; 1 case &#40;0&#46;7&#37;&#41; Spotted pattern&#44; 1 case &#40;0&#46;7&#37;&#41; Nucleolar pattern&#44; 3 cases &#40;2&#37;&#41; DFS-70 pattern&#44; 2 cases &#40;1&#46;9&#37;&#41; Sentriol pattern&#44; 3 cases &#40;2&#37;&#44; 9&#41; Midbody pattern&#46; It was rate 9&#46;09&#37; in 33 patients who were followed up with oral aphthae and later diagnosed as Beh&#231;et&#46; ANA patterns in patients with oral aphthae&#59; 1 case &#40;3&#37;&#41; DFS-70 pattern&#44; 1 case &#40;3&#46;03&#37;&#41; Midbody pattern&#46; There was no significant difference between the groups in terms of autoantibody positivity &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; When observed in terms of staining patterns&#44; there was no difference between the controls and Beh&#231;et&#39;s patients &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0020" class="elsevierStylePara elsevierViewall">Beh&#231;et&#39;s Disease is defined as a typical systemic vasculitic disease accompanied by recurrent oral and genital ulcers and uveitis&#46; However&#44; the etiopathogenesis of the disease is uncertain&#46; Genetic predisposition and environmental factors are usually blamed&#46; An autoimmunity process by abnormal T and B cell reactions and autoantigens is being focused on&#46; While inflammation in which Th1 type cytokine response and neutrophils play a role is detected in Beh&#231;et&#39;s Disease&#44; the hallmarks are no indication of the classic autoimmune disease&#44; such as predominance of the female sex and autoantibody positivity&#46; B cell numbers are normal but overall B cell activation is increased&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">4</span></a> However&#44; no autoantibody tests or specific autoantigen have been identified in patients&#46; The anti-endothelial cell antibody has been identified and alpha-enolase has been reported to be a possible antigen&#46; In addition&#44; kinetin&#44; which is an endoplasmic reticulum-dependent integral membrane protein&#44; has been reported as a possible autoantigen in Beh&#231;et&#39;s Disease&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Antinuclear antibodies &#40;ANA&#41; can be detected in several autoimmune diseases&#44; such as SLE &#40;Systemic Lupus Erythematosus&#41;&#44; Scleroderma&#44; and Sjogren&#39;s Syndrome in particular&#44; and lead to a diagnosis&#46; ANA tests can assist diagnosis by detecting antibodies that target various proteins found in the cell structure and proteins&#44; receptors&#44; and enzymes associated with mitosis as well as the cell nucleus&#46; While the increased tendency for autoimmunity in Beh&#231;et&#39;s Disease has led researchers to the detection of autoantibodies&#44; the presence of a specific autoantibody associated with Beh&#231;et&#39;s Disease has not been reported until now&#46; In one study&#44; it is stated that ANA prevalence was found high among Beh&#231;et&#39;s patients&#44; that a significant increase was observed compared to the control group&#44; and that this can be linked to polyclonal B cell activation&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">6</span></a> In the study by Chun et al&#46;&#44; it is reported that the rate of patients in whom ANA positivity was detected in a series of 554 cases was 8&#46;3&#37;&#44; but it is emphasized that the results are not related to the severity of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">7</span></a> In our series&#44; the rate of ANA-positive patients was 10&#46;7&#37;&#46; When the staining patterns of these patients are examined&#44; nonspecific patterns other than the homogenous&#44; speckle-type patterns observed frequently in autoimmune rheumatic diseases&#44; while few in numbers&#44; stand out&#46; Detected patterns include midbody&#44; centriole&#44; nucleolar&#44; and speckled staining and anti-DFS70 &#40;Anti-dense fine speckles 70&#41; staining&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In midbody staining&#44; intercellular bridge-like staining occurs in cells in anaphase or telophase&#46; In cells in metaphase&#44; granular staining in the chromosomal region can be noticed&#46; Until now&#44; it has not been associated with a specific autoimmune disease&#46; Autoantibody positivity is commonly found in low titers in healthy individuals and in diseases other than rheumatic diseases&#46; However&#44; such autoantibody positivity can sometimes also be a prodrome of a rheumatic disease that may be detected in the future&#46; Centrioles are at the center of the net-like structure &#40;spindle&#41; which is formed by microtubule and observed in mitosis&#46; Anti-centriole antibodies have been rarely detected in scleroderma spectrum diseases&#44; systemic sclerosis and Raynaud&#39;s phenomenon&#46; Hayakawa et al&#46; have reported finding them in a patient with systemic sclerosis and pulmonary hypertension&#46; In conclusion&#44; they report that mitosis-related antigens like centrioles can be associated with vascular damage&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">8</span></a> It is noteworthy that this pattern&#44; which was not detected in the healthy controls&#44; was detected in Beh&#231;et&#39;s patients in our series&#44; and that the disease&#44; in essence&#44; is a form of vasculitis&#46; Nucleolar staining and speckled staining&#44; on the other hand&#44; are usually detected in mixed connective tissue diseases such as scleroderma&#44; polymyositis&#44; rheumatoid arthritis&#44; and systemic lupus&#44; and have no known association with Beh&#231;et&#39;s Disease&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Anti DFS70 was first identified by Ochs et al&#46; in 1994 in the form of a thin speckled staining in HEp-2 cells and a positive reaction in the chromosomal region in mitotic cells and was given this name because it formed a band of about 70<span class="elsevierStyleHsp" style=""></span>kDa when immunoblotting was done&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">9</span></a> The target antigen of anti-DFS70 is identified as Lens Epithelium-Derived Growth Factor &#40;LEDGF&#47;p75&#41; and as transcription coactivator p75&#46; The antigen targeted by this antibody has important biological functions&#44; such as sustaining cell life and increasing the cell&#39;s resistance to cellular stress&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">10</span></a> The anti-DFS70 antibody can be detected in a variety of chronic inflammatory conditions&#44; in cancer patients&#44; and in a significant portion of the healthy population&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">11&#44;12</span></a> Beh&#231;et&#39;s Disease&#44; which forms the basis of our study group&#44; is an autoinflammatory disease as it is well known and anti-DFS70 positivity was found at a rate of 2&#46;1&#37; in our series of Beh&#231;et&#39;s patients and at a rate of 0&#46;7&#37; in the healthy controls&#44; and interestingly&#44; all of these patients were female&#46; In Japan&#44; DFS70 is reported at a rate of approximately 10&#37; among healthy people&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">11</span></a> but in our series&#44; this rate is much lower than in Japanese society&#46; The recognition of a DFS70 pattern in ANA testing is very important&#46; DFS70 can be found alongside anti-p80 coilin antibodies or SS-A positivity in rheumatoid diseases&#46; In their study on patients with Vogt-Koyanagi-Harada &#40;VKH&#41; Disease and Beh&#231;et&#39;s patients with panuveitis&#44; Yamada et al&#46; investigated LEDGF and found the anti lgG and anti-LEDGF detection rate as 66&#46;7&#37; in this group&#44; as 21&#46;6&#37; in healthy controls&#44; as 34&#37; in Beh&#231;et&#39;s patients with panuveitis&#44; and as 25&#46;0&#37; in sarcoidosis patients&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">13</span></a> LEDGF is a protein linked to the stress reaction and for this reason&#44; can increase in inflammatory lesions and break immune tolerance&#44; but the fact that it can be detected in healthy controls decreases the likelihood of its direct association with the disease&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The inflammatory process in Beh&#231;et&#39;s patients may trigger DFS70 positivity&#44; and centriole staining may be associated with vasculitis&#46; However&#44; our results also support the general belief that there is no highly specific autoantibody associated with Beh&#231;et&#39;s disease&#46; It is noteworthy&#44; however&#44; that ANA staining patterns&#44; the exact disease associations of which have not yet been revealed&#44; can be found more in these patients&#44; considering that chronic inflammatory reactions can lead to the breakdown of immune tolerance&#46; The treatment of the disease with immunosuppressants is related to the ability to suppress with these treatments the inflammation that occurs due to immune response and endothelial dysfunction&#46; There are still many unanswered questions regarding the pathogenesis of the disease&#46; The detection of nonspecific patterns in our results suggests an indirect relationship with the disease&#44; and the unknowns should continue to be investigated&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflict of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "titulo" => "Materials and method"
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    "fechaRecibido" => "2020-04-14"
    "fechaAceptado" => "2020-11-16"
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          "palabras" => array:3 [
            0 => "ANA staining patterns"
            1 => "Autoantibodies"
            2 => "Beh&#231;et&#39;s Disease"
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          "palabras" => array:3 [
            0 => "Patrones de tinci&#243;n del m&#233;todo ANA"
            1 => "Autoanticuerpos"
            2 => "Enfermedad de Beh&#231;et"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The autoinflammatory character of Beh&#231;et&#39;s Disease has led researchers to investigate the role of autoantibodies&#46; However&#44; no significant positive result has been reported for autoantibody tests for the disease&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Aims</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To investigate the specific and nonspecific staining patterns of Beh&#231;et&#39;s Disease &#40;BD&#41; patients&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">140 patients &#40;87 females&#44; 53 males&#41; with an average of 41&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3 years who were being followed up for Beh&#231;et&#39;s Disease&#44; and a control group consisting of a total of 736 &#40;464 females&#44; 272 males&#41; healthy volunteers made up of blood donors without any disease whose average age was 50&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4 years were included in the study&#46; Peripheral venous blood was collected from the patients and the sera were separated&#46; Patient sera were studied by indirect immunofluorescence antibody test &#40;IFA&#41; at a dilution of 1&#47;40 and 1&#47;100&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A total of 140 &#40;87 females&#44; 53 males&#41; Beh&#231;et&#39;s Disease patients and 736 &#40;464 females&#44; 272 males&#41; healthy controls were examined&#46; The rate of ANA positivity was 11&#46;6&#37; in the control group and 10&#46;7&#37; in the Beh&#231;et&#39;s Disease group&#46; In general&#44; no difference was detected between the patients and the healthy controls in terms of autoantibody positivity &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; However&#44; when examined in terms of patterns&#44; the low detection of DFS70 and the observation of centriole staining type patterns in Beh&#231;et&#39;s Disease patients was noteworthy &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Autoantibody tests&#44; which hold an important place in classic autoimmune diseases&#44; are not necessary for Beh&#231;et&#39;s patients&#44; but they should be examined in terms of nonspecific patterns&#46;</p></span>"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Antecedentes</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El car&#225;cter autoinflamatorio de la enfermedad de Beh&#231;et &#40;EB&#41; ha llevado a los investigadores a estudiar el rol de los autoanticuerpos&#46; Sin embargo&#44; no se ha reportado un resultado positivo significativo para las pruebas de autoanticuerpos&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Investigar los patrones de tinci&#243;n espec&#237;ficos y no espec&#237;ficos de los pacientes con EB&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se incluy&#243; en el estudio a 140 pacientes &#40;87 mujeres y 53 varones&#41; con una edad media de 41&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3 a&#241;os con seguimiento por EB&#44; y un grupo control que incluy&#243; a un total de 736 voluntarios sanos &#40;464 mujeres y 272 varones&#41; integrados por donantes de sangre sin enfermedad alguna&#44; con una edad media de 50&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4 a&#241;os&#46; Se extrajo sangre de vena perif&#233;rica a todos los pacientes&#44; separ&#225;ndose el suero&#44; que se estudi&#243; mediante el test de anticuerpos por inmunofluorescencia directa &#40;IFA&#41; a un factor de diluci&#243;n de 1&#47;40 y 1&#47;100&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se examin&#243; a un total de 140 pacientes &#40;87 mujeres y 53 varones&#41; con EB y 736 controles sanos &#40;464 mujeres y 272 varones&#41;&#46; La tasa de positividad de ANA fue del 11&#44;6&#37; en el grupo control y del 10&#44;7&#37; en el grupo de EB&#46; En general no se detect&#243; diferencia entre los pacientes y los controles sanos en t&#233;rminos de positividad de autoanticuerpos &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46; Sin embargo&#44; al realizarse el examen en t&#233;rminos de patrones&#44; fue destacable la baja detecci&#243;n de DFS70 y la observaci&#243;n de los patrones tipo tinci&#243;n de centriolos en los pacientes con EB &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusi&#243;n</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Los test de autoanticuerpos&#44; que ocupan una posici&#243;n importante en las enfermedades autoinmunes cl&#225;sicas&#44; no son necesarios para los pacientes con EB&#44; aunque deber&#237;an examinarse en t&#233;rminos de patrones no espec&#237;ficos&#46;</p></span>"
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            "identificador" => "abst0030"
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                    0 => array:2 [
                      "titulo" => "Criteria for diagnosis of Beh&#231;et&#39;s disease"
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                          "colaboracion" => "International study group of Beh&#231;et&#39;s disease"
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                        "tituloSerie" => "Lancet"
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                      "doi" => "10.1155/2012/607921"
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                        "tituloSerie" => "Patholog Res Int"
                        "fecha" => "2012"
                        "volumen" => "2012"
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