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HLA-B51 has been confirmed as the strongest risk factor for BD&#44; which was verified in various populations&#46; More recently studies have disclosed the association of many non-HLA genes with the BD&#44; such as chemokine receptor 1 &#40;CCR1&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">3</span></a> Vitamin D Receptor &#40;VDR&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">4</span></a> interleukin-23 &#40;IL-23&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">5</span></a> IL-23R and IL-12RB2&#44;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">3&#44;6</span></a> fork head box P3 &#40;Foxp3&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a> IL-2&#44; IL-4&#44; transforming growth factor &#40;TGF&#41;-beta&#44;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">8</span></a> IL-27<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">9</span></a> and IL-6<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">10</span></a> for BD&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">IL-6 is a multifunctional cytokine with a wide-range of biologic activities such as the regulation of the acute-phase response to infection&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">11</span></a> Dysregulation and dysfunction of IL-6 gene expression contributes to the inception of numerous diseases&#44; such as several types of cancer&#44; autoimmune disease for example rheumatoid arthritis &#40;RA&#41;&#44; type 1 diabetes &#40;T1D&#41;&#44; inflammatory bowel disease &#40;IBD&#41;&#44; multiple sclerosis &#40;MS&#41;&#44; and autoinflammatory disorders such as Beh&#231;et&#39;s disease &#40;BD&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">11&#44;12</span></a> According to previous studies&#44; it was found that IL-6 exerts its action via the activation of the JAK&#47;STAT &#40;Janus kinase&#47;signal transducer and activator of transcription&#41; and MAPK &#40;mitogenactivated protein kinase&#41; cascades&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">11&#44;13</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Previous studies have found four types of epigenetic mechanisms&#44; which are responsible for regulating the expression of genes including&#58; DNA methylation&#44; histone modification&#44; non-coding RNAs &#40;nc RNAs&#41; and chromatin remodeling&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">14&#8211;16</span></a> DNA methylation is an epigenetic alteration that efficiently controls gene expression via gene silencing&#44; and may significantly contribute to the risks of many multiplex diseases&#44; including cancer&#44; autoimmune disease&#44; and metabolic disorders&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">16&#8211;18</span></a> Recent researches of cytokine&#39;s gene expression have focused on the epigenetic alterations&#44; because the DNA methylation status at CpG sites is often related with cytokine expression changes&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">19</span></a> Decreasing of methylation is related with chromatin&#39;s open position&#44; but increasing of methylation corresponds to chromatin&#39;s closed status&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">20</span></a> Then&#44; the extent to which CpG islands methylation is associated with the level of cytokine expression&#46; Thus&#44; we questioned whether DNA methylation of IL-6 is reduced in BD T cells with modifying transcription factor recruitment&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Proinflammatory and anti-inflammatory agents are involved in the beginning and development of BD&#59; thus&#44; a comprehensive survey of the regulatory mechanism for the production of cytokines during the progression of BD is the most importance challenge&#46; IL-6 produced mainly by monocytes&#44; B cells&#44; T helper type 2 &#40;Th2&#41; and endothelial cells and plays an essential role in encouraging inflammation and stimulating the immune response&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">21</span></a> Also&#44; the production of IL-6 in the joint tissues is usually done in response to interleukin-1 beta &#40;IL-1&#946;&#41; and tumor necrosis factor alpha &#40;TNF-&#945;&#41; and is mostly performed by chondrocytes&#44; osteoblasts&#44; macrophages&#44; and adipocytes&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">22&#44;23</span></a> Also&#44; IL-6 is an important cytokine in BD pathogenesis as well as it plays a key role in differentiation of CD4&#43; T cells to Th17 cells&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">24</span></a> IL-6 is an inflammatory cytokine that has been associated in several immune-mediated inflammatory diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">25</span></a> IL-6 can encourage inflammation by increasing the production of inflammatory cytokines such as TNF-&#945;&#44; IL-1&#946; and other agents&#46; In addition&#44; this cytokine plays a key role by inhibiting the anti-inflammatory cytokines and interleukin-1 receptor antagonists &#40;IL-1Ra&#41; production&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">26&#44;27</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Evidence has indicated that IL-6 is involved in the pathogenesis of autoimmune disease&#46; In this study&#44; we analyzed the IL-6 expression in patient with BD in comparison with healthy groups&#46; Also&#44; we evaluated the methylation level of interleukin-6 in both healthy and patient groups&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods and materials</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients and healthy controls study group</span><p id="par0030" class="elsevierStylePara elsevierViewall">All specimens presented their written informed agreement for this study&#44; and the study protocol was permitted by the ethics committee of Tabriz University of Medical Sciences&#44; Tabriz&#44; Iran &#40;Permit Number&#58; TBZMED&#46;REC&#46;1394&#46;640&#41;&#46; The study group consisted of 51 Iranian patients with BD &#40;61&#46;7&#37; men and 38&#46;3&#37; women&#41;&#44; range 16&#8211;60 years and 61 healthy candidates&#46; The analysis of BD was based on the international study group criteria for BD&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">28</span></a> Features of the patients were evaluated at the time of diagnosis&#46; The control group composed of 61 healthy subjects who were matched with age&#44; gender&#44; and ethnic of patients &#40;59&#37; men versus 41&#37; women&#41;&#46; Healthy participants had no clinical or laboratory signs of autoimmune or inflammatory diseases&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">DNA&#44; RNA isolation and RT-PCR method</span><p id="par0035" class="elsevierStylePara elsevierViewall">Peripheral blood mononuclear cells &#40;PBMCs&#41; were extracted from EDTA blood tubes by Ficoll &#40;Lymphodex&#44; Inno -Train&#44; Germany&#41; density-gradient centrifugation and directly stored at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C until use&#46; Genomic DNA samples of BD and healthy controls were isolated by using the rapid genomic DNA extraction &#40;RGDE&#41; method from the peripheral blood collected in tubes containing EDTA&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">29</span></a> Total RNA was extracted from the PBMCs according to the protocol of TRIzol &#40;Invitrogen&#44; San Diego&#44; CA&#41;&#44; followed by reverse transcription using the reverse transcription reagent kit &#40;Thermo Fisher scientific&#44; USA&#41;&#46; Then&#44; purity and concentration of total RNA were estimated by nanodrop ND1000 and at 260&#8211;280<span class="elsevierStyleHsp" style=""></span>nm purity of RNAs were assessed&#46; The entirety of total RNA was showed by gel electrophoresis of the individual samples on a 1&#37; agarose gel&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Primer design</span><p id="par0040" class="elsevierStylePara elsevierViewall">IL-6 gene sequence and data about promoter were picked up from the National Center for Biotechnology Information &#40;NCBI&#41; and eukaryotic promoter database &#40;EPD&#41;&#46; For IL-6 mRNA sequence&#44; the primer pairs were designed using OLIGO7 Software&#44; &#40;Molecular Biology Insights&#44; Inc&#46;&#44; Cascade&#44; CO&#46;&#44; USA&#41; and MethPrimer online software&#46; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; Also&#44; IL-6 gene Promoter CpG islands were predicted with eukaryotic promoter database &#40;EPD&#41;&#46; One pairs of IL-6 primer were designed using PrimerQuest tool to amplify CpG islands of TSS &#40;transcription start site&#41; upstream &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Real-time PCR</span><p id="par0045" class="elsevierStylePara elsevierViewall">Peripheral blood mononuclear cells &#40;PBMCs&#41; were extracted from EDTA blood tubes by Ficoll &#40;Lymphodex&#44; Inno -Train&#44; Germany&#41; density-gradient centrifugation&#46; Total RNA was extracted from the PBMCs using TRIzol &#40;Invitrogen&#44; San Diego&#44; CA&#41;&#44; followed by reverse transcription using the reverse transcription reagent kit &#40;thermofisher Scientific&#44; USA&#41; and then the expression of IL-10 was measured by MIC real-time instrument &#40;Bio Molecular Systems&#44; AUSTRALIA&#41;&#46; The following sequences of the sense and antisense primers of IL-6 were used&#58; forward 5&#8242;-GCAGAAAACAACCTGAACC-3&#8242; and reverse 5&#8242;-GCTTGTTCCTCACTACTCTC-3&#8242;&#46; &#946;-Actin was chosen as the internal reference for expression and copy number variation detection and its expression was evaluated by the following primers in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Relative expression levels of IL-6 were calculated using the &#916;&#916;Ct formula&#46; All tests were performed in at three biological repeats&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Methylated DNA immunoprecipitation assessment</span><p id="par0050" class="elsevierStylePara elsevierViewall">One pair of primers were designed using Primer Quest Tool and methMarker &#40;PREMIER Biosoft&#44; CA&#44; USA&#41; to amplify CpG islands of TSS &#40;transcription start site&#41; upstream &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Methylated DNA immunoprecipitation &#40;MeDIP&#41; was performed using EpiQuik&#8482; MeDIP Ultra Kit &#40;Epigentek&#44; Farmingdale&#44; NY&#44; USA&#41;&#46; This Kit contains all components essential for doing a successful MeDIP procedure using DNA extracted from PBMCs such as a methylated DNA &#40;mDNA&#41; control and an unmethylated DNA &#40;unDNA&#41; control and control primers that can be used with the control DNA to exhibit the enrichment efficacy and specificity for methylated DNA&#46; The extracted DNA is sonicated to produce random fragments ranging in size from 200 to 800<span class="elsevierStyleHsp" style=""></span>bp using the BANDELIN sonicator &#40;UVV&#58; 3200&#44; Germany&#41; for 15 cycles of 20<span class="elsevierStyleHsp" style=""></span>s on&#47;20<span class="elsevierStyleHsp" style=""></span>s off&#46; Fragment size was confirmed by electrophoresis on a 1&#46;5&#37; agarose gel &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Then&#44; 1<span class="elsevierStyleHsp" style=""></span>&#956;g of DNA is used for following MeDIP enrichment&#46; This method was performed by 5<span class="elsevierStyleHsp" style=""></span>&#956;g of fragmented genomic DNA was diluted to 400<span class="elsevierStyleHsp" style=""></span>&#956;l in TE buffer and DNA was denatured at 95<span class="elsevierStyleHsp" style=""></span>&#176;C for 5<span class="elsevierStyleHsp" style=""></span>min followed by immediate cooling on ice for 5<span class="elsevierStyleHsp" style=""></span>min&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">MeDIP-QPCR amplification was carried out using 1<span class="elsevierStyleHsp" style=""></span>&#956;l of eluted DNA in a 20<span class="elsevierStyleHsp" style=""></span>&#956;l PCR reaction along with primer sets&#46; The assays were performed in three replicates and relative methylation fold change was measured for each sample with FE&#37; method which is referred to below&#46; QPCR cycles and the timing steps include an activation cycle&#44; a denaturation cycle at 95<span class="elsevierStyleHsp" style=""></span>&#176;C for 2<span class="elsevierStyleHsp" style=""></span>min and 40 cycles of extension at 95<span class="elsevierStyleHsp" style=""></span>&#176;C for 10<span class="elsevierStyleHsp" style=""></span>s&#44; 54<span class="elsevierStyleHsp" style=""></span>&#176;C for 30<span class="elsevierStyleHsp" style=""></span>s&#44; and finally 72<span class="elsevierStyleHsp" style=""></span>&#176;C for 20<span class="elsevierStyleHsp" style=""></span>s&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The fold enrichment &#40;FE&#41; of IL-6 fragments was calculated using a formula described in manufacture protocol of this kit using a ratio of amplification efficiency of the MeDIP sample over that of non-immune IgG&#58;<elsevierMultimedia ident="eq0005"></elsevierMultimedia></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0065" class="elsevierStylePara elsevierViewall">Statistical analysis was performed using SPSS software version 17&#46;0 &#40;SPSS&#44; Chicago&#44; IL&#44; USA&#41;&#46; Normal distributions were tested with the Kolmogorov&#8211;Smirnov test with Lilliefors correction&#46; Quantitative data were presented as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation &#40;SD&#41;&#46; The differences in mRNA and serum levels of IL-6 between control and BD groups were evaluated by Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test&#46; <span class="elsevierStyleItalic">p</span>-Value &#60;0&#46;05 was considered as significant difference&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Subject characteristics</span><p id="par0070" class="elsevierStylePara elsevierViewall">Patient&#39;s characteristics are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; The patient group consisted of 29 males and 18 females&#44; with a mean age of 38&#46;02<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;25 years&#46; The control subjects included 37 males and 24 females and had a mean age of 37&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;5 years&#46; No significant difference was observed in age between patients with BD and controls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Real-time quantitative PCR for IL-6 gene</span><p id="par0075" class="elsevierStylePara elsevierViewall">In order to compare the level of interleukin-6 &#40;IL-6&#41; gene expression in two groups of BD and healthy subjects&#44; an independent <span class="elsevierStyleItalic">T</span>-test was adopted&#44; taking into consideration the data obtained by employing Kolmogorov&#8211;Smirnov test&#44; was normal &#40;<span class="elsevierStyleItalic">p</span>-value &#62;0&#46;05&#41;&#46; The obtained results were indicative of significant difference between two groups &#40;<span class="elsevierStyleItalic">p</span>-value &#60;0&#46;05&#41;&#46; As we expected&#44; the level of gene expression showed increase in BD individuals group in comparison with healthy group &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; Also in the patient groups&#44; we analyzed the relationship between gene expression and clinical features&#46; As the results indicated&#44; the gene expression level of IL-6 was significantly different in phlebitis section that is shown as bold in table&#46; Interleukin-6 gene expression was also significantly increased in individuals with positive phlebitis &#40;<span class="elsevierStyleItalic">p</span>-value &#60;0&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Methylation status and mRNA expression</span><p id="par0080" class="elsevierStylePara elsevierViewall">We evaluated the association between the methylation pattern of the IL-6 gene and mRNA expression&#46; The mRNA &#40;1&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;3 versus 0&#46;77<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;14&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; of IL6 was significantly higher in the patients with BD than healthy groups&#46; Also&#44; in order to compare the methylation status of interleukin-6 &#40;IL-6 in two groups of BD and healthy individuals&#44; an independent <span class="elsevierStyleItalic">T</span>-test was adopted&#44; taking into consideration the data obtained by employing Kolmogorov&#8211;Smirnov test&#44; was normal &#40;<span class="elsevierStyleItalic">p</span>-value &#62;0&#46;05&#41;&#46; The results showed that there was a statistical difference between both groups in terms of methylation rate of interleukin-6 gene &#40;<span class="elsevierStyleItalic">p</span>-value &#60;0&#46;001&#41;&#46; In line with our expectations&#44; the methylation ratio of IL-6 revealed decrease in BD individuals group in comparison with healthy group &#40;0&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;08 versus 0&#46;77<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;09&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Also in the patient groups&#44; we analyzed the relationship between methylation level and clinical features&#46; As the results showed&#44; the methylation levels had significant differences in the arthritis section&#46; In addition&#44; the methylation level of IL-6 was lower in positive group of arthritis than the negative value &#40;<span class="elsevierStyleItalic">p</span>-value &#60;0&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">Behcet&#39;s disease &#40;BD&#41; is an autoinflammatory disease of unknown etiology&#46; Cytokines involved can be classified as Th1&#44; Th2&#44; Th17&#44; Treg types&#44; chemokines and others proinflammatory agents&#46; The cytokine network plays an important role in the pathogenesis of diseases&#44; especially autoimmune disorders&#44; as well in the formation and progression of lesions of the organism and may be blocked by one of the basic links of cytokines&#44; which in turn may obtain the critical clues to view the target therapy program of cytokine in BD&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">30</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Chronic inflammation and responses creates a main mechanism for autoimmune disease&#46; The definite pathways by which the inflammation causes autoimmune are not completely recognized&#46; IL-6 is a multifunctional cytokine produced and released by inflammatory cells and can trigger intracellular transcription factors leading to gene expression&#44; cell division&#44; apoptosis processes and inflammation response&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">25&#44;31&#44;32</span></a> Persistent differences in the production of IL-6 have been identified among different individuals in various populations with polymorphism at the end of 5&#8242; region<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">33</span></a> and the genetic associations of IL-6 polymorphism have been identified with rates of infections&#44; inflammation and immune diseases&#46; This suggested that the production rate of this cytokine is a risk factor for most diseases and their condition&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a> However&#44; to date&#44; the role of epigenetic variable has not been reported in IL-6 gene on Beh&#231;et&#39;s disease&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">There are some findings indicated that IL-6 may stimulate immune response through the effect on the expression of effective genes by altering patterns of DNA methylation&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">35</span></a> On the other hand&#44; IL-6 production is regulated by methylation of the IL-6 gene promoter&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">35</span></a> DNA demethylation is a property of transcriptionally active genes&#44; and our results are fit with the view that the level of methylation is essential in the regulation of the IL-6 production in patients with BD and could participate in production of this cytokine as seen in BD and other autoimmune disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">35&#44;36</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">In a study of 51 BD patients aged 16&#8211;60<span class="elsevierStyleHsp" style=""></span>y&#44; we examined the level of promoter methylation of IL-6 in association with demographic and clinical risk factors such as gender and severe BD as well as inflammation markers&#46; As the results showed&#44; the gene expression level of IL-6 was significantly different in phlebitis section&#46; IL-6 gene expression was also significantly increased in individuals with positive phlebitis&#46; Furthermore&#44; in order to compare the methylation status of IL-6 in two groups of BD and healthy individuals&#44; the results showed that there was a statistical significant difference between both groups in terms of methylation rate of IL-6 gene &#40;<span class="elsevierStyleItalic">p</span>-value &#60;0&#46;001&#41;&#46; According to our results&#44; there was no relationship between the gene expression and its methylation in different parts of the clinical profile&#46; One of the possible reasons for these results is that our population sample size was small&#44; and if we selected a larger population size&#44; our results may be more meaningful&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Epigenetic differences&#44; especially the level of IL-6 methylation between BD patients and healthy group&#44; can be an initial manifestation suggested an increased risk of BD prevalence with the low methylation level of IL-6 promoter&#46; On the other hand&#44; this difference can be considered as a main manipulation for BD prevention or treatment&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Scientists from China reported in previous studies that a significantly higher level of IL-6 in cerebrospinal fluid &#40;CSF&#41; had been detected in Chinese patients with active BD with central nervous system &#40;CNS&#41; involvement&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">37</span></a> Also&#44; in a previous study about the methylation level of the IL-6 promoter in patients with RA in comparison with healthy groups&#44; the results indicated that a single CpG site at -1&#44;181 was considerably less methylated in subjects with rheumatoid arthritis &#40;RA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">35</span></a> Some pioneering studies demonstrated that dysregulation of immune system is related to aging&#46; Furthermore&#44; these results revealed that the level of IL-6 expression was intensified with age in animals model such as mice&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">38</span></a> It has also been shown that the level of IL-6 are much higher in serum&#44; synovial fluid and synovial tissue in patients with severe RA compared with subjects without inflammatory arthritis which indicates that it is related to the activity of disease&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a> Some contradictory results reported in previous studies&#46; A decrease or no effect of age on IL-6 production had been shown already&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">40</span></a> According to the results of this clinical study&#44; significant difference could not be seen between patients when dichotomized by age&#46; These diverse results may be caused by the differences in experimental conditions and the health status of subjects in various investigations&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">These results recommend that the level of methylation in promoter region of gene may be a key mechanism for regulation of IL-6 gene expression in BD and IL-6 CpG island hypomethylation might be involved in the progression of BD&#46; Besides&#44; according to the results&#44; molecular methods such as the analysis of DNA methylation could recognize in early detection by changes in the genotype and genome sequencing&#46; This may be used for early diagnosis and initiation of rapid therapies&#46; Therefore&#44; IL-6 can be used as a molecular marker for the diagnosis of Behcet&#39;s patients&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conclusion</span><p id="par0125" class="elsevierStylePara elsevierViewall">Regarding the results of expression and methylation of IL-6 in this study&#44; it may be considered that methylation may be as one of the regulatory mechanisms involved in regulating gene expression&#46; Generally&#44; epigenetic alteration such as hypermethylation of IL-6 gene may be a potent therapeutic approach in controlling BD&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflict of interest</span><p id="par0130" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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            3 => "Metilaci&#243;n"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">IL-6 mRNA expression is significantly high in many autoimmune diseases such as Beh&#231;et&#39;s disease&#59; this is often related with more aggressive phenotypes&#46; Nevertheless&#44; the essential molecular process for its high expression has not been completely realized&#46; The aim of this study was undertaken to estimate the gene copy number variation and promoter methylation to IL-6&#39;s high expression&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This study was performed on 51 patients and 61 healthy controls&#46; Initially&#44; DNA and RNA were extracted from all specimens&#46; Promoter methylation levels of IL-6 were evaluated by MeDIP-qPCR technique&#46; Also&#44; IL-6 gene expression was measured by Real-time PCR&#46; After that&#44; we evaluated the relationship between gene expression and methylation&#44; as well as their relationship with clinical specification&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">As we expected&#44; the expression level of IL-6 gene increased significantly in the patient group compared to the healthy subjects&#46; Also&#44; the relative promoter methylation level of the IL-6 mRNA was significantly lower in patient group compared to healthy group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Discussion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">We disclosed that the promoter hypomethylation may be considered as one of the main defects for IL-6 mRNA high expression in patients with Beh&#231;et&#39;s disease&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
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            "identificador" => "abst0015"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La expresi&#243;n de ARNm de IL-6 es significativamente elevada en muchas enfermedades autoinmunes&#44; tales como el s&#237;ndrome de Beh&#231;et&#44; y ello se relaciona a menudo con fenotipos m&#225;s agresivos&#46; Sin embargo&#44; no se ha comprendido plenamente el proceso molecular esencial para esta expresi&#243;n elevada&#46; El objetivo de este estudio fue la estimaci&#243;n de la variaci&#243;n del n&#250;mero de copias del gen&#44; y la metilaci&#243;n del promotor de la expresi&#243;n elevada de IL-6&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Este estudio se realiz&#243; en 51 pacientes y 61 controles sanos&#46; Al inicio&#44; se extrajo ADN y ARN de todas las muestras&#46; Se evaluaron los niveles de metilaci&#243;n del promotor de IL-6 mediante la t&#233;cnica MeDIP-qPCR&#46; Tambi&#233;n se midi&#243; la expresi&#243;n del gen IL-6 mediante PCR a tiempo real&#46; Tras ello&#44; evaluamos la relaci&#243;n entre la expresi&#243;n del gen y la metilaci&#243;n&#44; as&#237; como su relaci&#243;n con la especificaci&#243;n cl&#237;nica&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Seg&#250;n lo previsto&#44; el nivel de expresi&#243;n del gen IL-6 se increment&#243; significativamente en el grupo de pacientes&#44; con respecto a los sujetos sanos&#46; Tambi&#233;n encontramos que el nivel relativo de metilaci&#243;n del promotor de ARNm de IL-6 fue considerablemente menor en el grupo de pacientes&#44; con respecto al grupo sano &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Discusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Concluimos que la hipometilaci&#243;n del promotor puede considerarse uno de los defectos principales de la expresi&#243;n elevada de ARNm de IL-6&#44; en los pacientes con s&#237;ndrome de Beh&#231;et&#46;</p></span>"
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                  \t\t\t\t">GCAGAAAACAACCTGAACCGCTTGTTCCTCACTACTCTC&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">GGTGAAGGTGACAGCAGTTGGGGTGGCTTTTAGGAT&nbsp;\t\t\t\t\t\t\n
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">As shown in the table&#44; items that have a statistically significant difference are shown as bold&#46; IL-6&#58; interleukin-6&#44; SD&#58; standard deviation&#44; HLA&#58; Human leukocyte antigen&#44; BD&#58; Beh&#231;et&#39;s disease&#44; EN&#58; Erythema Nodosum&#46;</p>"
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;29&#41; 61&#46;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;41</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;18</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;18&#41; 38&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;05<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;72<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">HLA-B5-</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;33&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;36</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;31</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;21&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;35<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;65<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">HLA-B51</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;15&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;9</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;5</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;13&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;65<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">HLA-B27</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;34<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;17</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;69<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;88</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;44&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;88<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Oral aphtha</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45 &#40;96&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;35</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;5</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Genital ulcer</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;51&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;78</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;18</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;49&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;66<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Arthritis</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;19&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;97</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle"><span class="elsevierStyleBold">0&#46;04</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38 &#40;81&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sever B&#46;D&#46;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;64&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;41</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;69<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;41</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;36&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;91<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Severe eye involvement</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;22&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;9</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;64</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 &#40;78&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">EN</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;16&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;62</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;94</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38 &#40;84&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Phlebitis</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;11&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle"><span class="elsevierStyleBold">0&#46;04</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="middle">0&#46;29</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41 &#40;89&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Ocular</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No eye involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;23&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="char" valign="middle">0&#46;44</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="char" valign="middle">0&#46;26</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Serum levels of TNF-&#945;&#44; sIL-2R&#44; IL-6&#44; and IL-8 are increased and associated with elevated lipid peroxidation in patients with Beh&#231;et&#39;s disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "C&#46; Evereklioglu"
                            1 => "H&#46; Er"
                            2 => "Y&#46; T&#252;rk&#246;z"
                            3 => "M&#46; &#199;ekmen"
                          ]
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Mediat Inflamm"
                        "fecha" => "2002"
                        "volumen" => "11"
                        "paginaInicial" => "87"
                        "paginaFinal" => "93"
                      ]
                    ]
                  ]
                ]
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            10 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "11"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Principles of interleukin &#40;IL&#41;-6-type cytokine signalling and its regulation"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "P&#46;C&#46; Heinrich"
                            1 => "I&#46; Behrmann"
                            2 => "H&#46; Serge"
                            3 => "H&#46;M&#46; Hermanns"
                            4 => "G&#46; M&#252;ller-Newen"
                            5 => "F&#46; Schaper"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1042/BJ20030407"
                      "Revista" => array:7 [
                        "tituloSerie" => "Biochem J"
                        "fecha" => "2003"
                        "volumen" => "374"
                        "paginaInicial" => "1"
                        "paginaFinal" => "20"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12773095"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0167527315300796"
                          "estado" => "S300"
                          "issn" => "01675273"
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                  ]
                ]
              ]
            ]
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              "identificador" => "bib0260"
              "etiqueta" => "12"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cytokines in Behcet&#39;s disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "N&#46; Sayinalp"
                            1 => "O&#46; Ozcebe"
                            2 => "O&#46; Ozdemir"
                            3 => "I&#46; Haznedaro&#287;lu"
                            4 => "S&#46; D&#252;ndar"
                            5 => "S&#46; Kirazli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Rheumatol"
                        "fecha" => "1996"
                        "volumen" => "23"
                        "paginaInicial" => "321"
                        "paginaFinal" => "322"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8882039"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Interleukin-6-type cytokine signalling through the gp130&#47;Jak&#47;STAT pathway"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "P&#46;C&#46; Heinrich"
                            1 => "I&#46; Behrmann"
                            2 => "G&#46; M&#252;ller-Newen"
                            3 => "F&#46; Schaper"
                            4 => "L&#46; Graeve"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Biochem J"
                        "fecha" => "1998"
                        "volumen" => "334"
                        "paginaInicial" => "297"
                        "paginaFinal" => "314"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "14"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Epigenetic modifications of interleukin-6 in synovial fibroblasts from osteoarthritis patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Yang"
                            1 => "S&#46; Zhou"
                            2 => "C&#46; Wang"
                            3 => "Y&#46; Huang"
                            4 => "H&#46; Li"
                            5 => "Y&#46; Wang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/srep43592"
                      "Revista" => array:5 [
                        "tituloSerie" => "Sci Rep"
                        "fecha" => "2017"
                        "volumen" => "7"
                        "paginaInicial" => "43592"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28262826"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0275"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "KLF4 modulates expression of IL-6 in dendritic cells via both promoter activation and epigenetic modification"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46;M&#46; Rosenzweig"
                            1 => "J&#46;D&#46; Glenn"
                            2 => "P&#46;A&#46; Calabresi"
                            3 => "K&#46;A&#46; Whartenby"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Biol Chem"
                        "fecha" => "2013"
                        "volumen" => "288"
                        "paginaInicial" => "23868"
                        "paginaFinal" => "23874"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epigenetic alterations in chronic disease focusing on Beh&#231;et&#39;s disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Alipour"
                            1 => "M&#46; Nouri"
                            2 => "E&#46; Sakhinia"
                            3 => "N&#46; Samadi"
                            4 => "N&#46; Roshanravan"
                            5 => "A&#46; Ghavami"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.biopha.2017.04.106"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biomed Pharmacother"
                        "fecha" => "2017"
                        "volumen" => "91"
                        "paginaInicial" => "526"
                        "paginaFinal" => "533"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28482290"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A gene hypermethylation profile of human cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Esteller"
                            1 => "P&#46;G&#46; Corn"
                            2 => "S&#46;B&#46; Baylin"
                            3 => "J&#46;G&#46; Herman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Cancer Res"
                        "fecha" => "2001"
                        "volumen" => "61"
                        "paginaInicial" => "3225"
                        "paginaFinal" => "3229"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11309270"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mechanisms of disease&#58; the developmental origins of disease and the role of the epigenotype"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "S&#46;E&#46; Ozanne"
                            1 => "M&#46; Const&#226;ncia"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Nat Rev Endocrinol"
                        "fecha" => "2007"
                        "volumen" => "3"
                        "paginaInicial" => "539"
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673614617748"
                          "estado" => "S300"
                          "issn" => "01406736"
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                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Methylation and demethylation in the regulation of genes&#44; cells&#44; and responses in the immune system"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "D&#46;R&#46; Fitzpatrick"
                            1 => "C&#46;B&#46; Wilson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s1521-6616(03)00205-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Immunol"
                        "fecha" => "2003"
                        "volumen" => "109"
                        "paginaInicial" => "37"
                        "paginaFinal" => "45"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14585274"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Identification of a coordinate regulator of interleukins 4&#44; 13&#44; and 5 by cross-species sequence comparisons"
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46;G&#46; Loots"
                            1 => "R&#46;M&#46; Locksley"
                            2 => "C&#46;M&#46; Blankespoor"
                            3 => "Z&#46;-E&#46; Wang"
                            4 => "W&#46; Miller"
                            5 => "E&#46;M&#46; Rubin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1126/science.288.5463.136"
                      "Revista" => array:6 [
                        "tituloSerie" => "Science"
                        "fecha" => "2000"
                        "volumen" => "288"
                        "paginaInicial" => "136"
                        "paginaFinal" => "140"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10753117"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0305"
              "etiqueta" => "21"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "IL-6&#58; a regulator of the transition from neutrophil to monocyte recruitment during inflammation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "G&#46; Kaplanski"
                            1 => "V&#46; Marin"
                            2 => "F&#46; Montero-Julian"
                            3 => "A&#46; Mantovani"
                            4 => "C&#46; Farnarier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s1471-4906(02)00013-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Trends Immunol"
                        "fecha" => "2003"
                        "volumen" => "24"
                        "paginaInicial" => "25"
                        "paginaFinal" => "29"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12495721"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0310"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Interleukin-1&#946; induces synthesis and secretion of interleukin-6 in human chondrocytes"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Bender"
                            1 => "H&#46;-D&#46; Haubeck"
                            2 => "E&#46; Van de Leur"
                            3 => "G&#46; Dufhues"
                            4 => "X&#46; Schiel"
                            5 => "J&#46; Lauwerijns"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "FEBS Lett"
                        "fecha" => "1990"
                        "volumen" => "263"
                        "paginaInicial" => "321"
                        "paginaFinal" => "324"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases&#44; matrix metalloproteinases&#44; and other destructive and inflammatory responses in osteoarthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
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                            1 => "S&#46;D&#46; Wainwright"
                            2 => "S&#46; Lauder"
                            3 => "N&#46; Amos"
                            4 => "C&#46;E&#46; Hughes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/ar2099"
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                        "tituloSerie" => "Arthritis Res Ther"
                        "fecha" => "2006"
                        "volumen" => "8"
                        "paginaInicial" => "R187"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17177994"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0320"
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                0 => array:2 [
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                    0 => array:2 [
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                          "etal" => true
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                            1 => "S&#46;W&#46; Kim"
                            2 => "C&#46;M&#46; Moon"
                            3 => "J&#46;J&#46; Park"
                            4 => "T&#46;I&#46; Kim"
                            5 => "W&#46;H&#46; Kim"
                          ]
                        ]
                      ]
                    ]
                  ]
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                    0 => array:2 [
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                        "tituloSerie" => "Life Sci"
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                        "volumen" => "90"
                        "paginaInicial" => "740"
                        "paginaFinal" => "746"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22483685"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0002914916305616"
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                          "issn" => "00029149"
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                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0325"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "IL-6 in autoimmune disease and chronic inflammatory proliferative disease"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "K&#46; Ishihara"
                            1 => "T&#46; Hirano"
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s1359-6101(02)00027-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cytokine Growth Factor Rev"
                        "fecha" => "2002"
                        "volumen" => "13"
                        "paginaInicial" => "357"
                        "paginaFinal" => "368"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12220549"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Z&#46; Xing"
                            1 => "J&#46; Gauldie"
                            2 => "G&#46; Cox"
                            3 => "H&#46; Baumann"
                            4 => "M&#46; Jordana"
                            5 => "X&#46;-F&#46; Lei"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI1368"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Clin Investig"
                        "fecha" => "1998"
                        "volumen" => "101"
                        "paginaInicial" => "311"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9435302"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Interleukin 1 receptor antagonist &#40;IL-1Ra&#41; is an acute-phase protein"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            2 => "D&#46; Eidlen"
                            3 => "W&#46;P&#46; Arend"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI119488"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Clin Investig"
                        "fecha" => "1997"
                        "volumen" => "99"
                        "paginaInicial" => "2930"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9185517"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Validation of the International Study Group criteria for Beh&#231;et&#39;s disease"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "T&#46; O&#8217;Neill"
                            1 => "A&#46; Rigby"
                            2 => "A&#46; Silman"
                            3 => "C&#46; Barnes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rheumatology"
                        "fecha" => "1994"
                        "volumen" => "33"
                        "paginaInicial" => "115"
                        "paginaFinal" => "117"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rapid genomic DNA extraction &#40;RGDE&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46;M&#46; Ali"
                            1 => "S&#46; Mahnaz"
                            2 => "T&#46; Mahmood"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Forensic Sci Int&#58; Genet Suppl Ser"
                        "fecha" => "2008"
                        "volumen" => "1"
                        "paginaInicial" => "63"
                        "paginaFinal" => "65"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cytokines and Behcet&#39;s disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Z&#46; Zhou"
                            1 => "S&#46; Chen"
                            2 => "N&#46; Shen"
                            3 => "Y&#46; Lu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.autrev.2011.12.005"
                      "Revista" => array:6 [
                        "tituloSerie" => "Autoimmun Rev"
                        "fecha" => "2012"
                        "volumen" => "11"
                        "paginaInicial" => "699"
                        "paginaFinal" => "704"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22197901"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Interplay between IFN-&#947; and IL-6 signaling governs neutrophil trafficking and apoptosis during acute inflammation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;M&#46; McLoughlin"
                            1 => "J&#46; Witowski"
                            2 => "R&#46;L&#46; Robson"
                            3 => "T&#46;S&#46; Wilkinson"
                            4 => "S&#46;M&#46; Hurst"
                            5 => "A&#46;S&#46; Williams"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI17129"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Investig"
                        "fecha" => "2003"
                        "volumen" => "112"
                        "paginaInicial" => "598"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12925700"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S1525861013003034"
                          "estado" => "S300"
                          "issn" => "15258610"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Roles of STAT3 in mediating the cell growth&#44; differentiation and survival signals relayed through the IL-6 family of cytokine receptors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "T&#46; Hirano"
                            1 => "K&#46; Ishihara"
                            2 => "M&#46; Hibi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/sj.onc.1203551"
                      "Revista" => array:6 [
                        "tituloSerie" => "Oncogene"
                        "fecha" => "2000"
                        "volumen" => "19"
                        "paginaInicial" => "2548"
                        "paginaFinal" => "2556"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10851053"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0365"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effect of novel polymorphisms in the interleukin-6 &#40;IL-6&#41; gene on IL-6 transcription and plasma IL-6 levels&#44; and an association with systemic-onset juvenile chronic arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Fishman"
                            1 => "G&#46; Faulds"
                            2 => "R&#46; Jeffery"
                            3 => "V&#46; Mohamed-Ali"
                            4 => "J&#46;S&#46; Yudkin"
                            5 => "S&#46; Humphries"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI2629"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Clin Investig"
                        "fecha" => "1998"
                        "volumen" => "102"
                        "paginaInicial" => "1369"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9769329"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Novel IL-6 haplotypes and disease association"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Fife"
                            1 => "E&#46; Ogilvie"
                            2 => "D&#46; Kelberman"
                            3 => "J&#46; Samuel"
                            4 => "A&#46; Gutierrez"
                            5 => "S&#46; Humphries"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/sj.gene.6364186"
                      "Revista" => array:6 [
                        "tituloSerie" => "Genes Immunity"
                        "fecha" => "2005"
                        "volumen" => "6"
                        "paginaInicial" => "367"
                        "paginaFinal" => "370"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15815691"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Methylation status of a single CpG site in the IL6 promoter is related to IL6 messenger RNA levels and rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "C&#46;J&#46; Nile"
                            1 => "R&#46;C&#46; Read"
                            2 => "M&#46; Akil"
                            3 => "G&#46;W&#46; Duff"
                            4 => "A&#46;G&#46; Wilson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Arthritis Rheumatol"
                        "fecha" => "2008"
                        "volumen" => "58"
                        "paginaInicial" => "2686"
                        "paginaFinal" => "2693"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Interleukin-6 &#40;IL-6&#41; in patients with Beh&#231;et&#39;s disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Yamakawa"
                            1 => "Y&#46; Sugita"
                            2 => "T&#46; Nagatani"
                            3 => "S&#46; Takahashi"
                            4 => "T&#46; Yamakawa"
                            5 => "S&#46;-i&#46; Tanaka"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/0923-1811(95)00439-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Dermatol Sci"
                        "fecha" => "1996"
                        "volumen" => "11"
                        "paginaInicial" => "189"
                        "paginaFinal" => "195"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8785169"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anticardiolipin antibodies and interleukin-6 in cerebrospinal fluid and blood of Chinese patients with neuro-Beh&#231;et&#39;s syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "C&#46; Wang"
                            1 => "C&#46; Chuang"
                            2 => "C&#46; Chen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Rheumatol"
                        "fecha" => "1991"
                        "volumen" => "10"
                        "paginaInicial" => "599"
                        "paginaFinal" => "602"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1483312"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "38"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Age-associated increase in interleukin 6 in MRL&#47;lpr mice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46; Tang"
                            1 => "T&#46; Matsuda"
                            2 => "S&#46; Akira"
                            3 => "N&#46; Nagata"
                            4 => "S&#46; Ikehara"
                            5 => "T&#46; Hirano"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/intimm/3.3.273"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int Immunol"
                        "fecha" => "1991"
                        "volumen" => "3"
                        "paginaInicial" => "273"
                        "paginaFinal" => "278"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2049341"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "In situ hybridization of IL-6 in rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "N&#46; Wood"
                            1 => "J&#46; Symons"
                            2 => "E&#46; Dickens"
                            3 => "G&#46; Duff"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2249.1992.tb02972.x"
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                        "tituloSerie" => "Clin Exp Immunol"
                        "fecha" => "1992"
                        "volumen" => "87"
                        "paginaInicial" => "183"
                        "paginaFinal" => "189"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1531188"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0400"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Interleukin-6 production does not increase with age"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46;A&#46; Beharka"
                            1 => "M&#46; Meydani"
                            2 => "D&#46; Wu"
                            3 => "L&#46;S&#46; Leka"
                            4 => "A&#46; Meydani"
                            5 => "S&#46;N&#46; Meydani"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Gerontol Ser A&#58; Biol Sci Med Sci"
                        "fecha" => "2001"
                        "volumen" => "56"
                        "paginaInicial" => "B81"
                        "paginaFinal" => "B88"
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
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