{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:50:48Z","timestamp":1791435048577,"version":"4.3.3"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,5,29]],"date-time":"2018-05-29T00:00:00Z","timestamp":1527552000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["FKZ 01ER0812"],"award-info":[{"award-number":["FKZ 01ER0812"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["FKZ 01ER0813"],"award-info":[{"award-number":["FKZ 01ER0813"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["FKZ 01ER0828"],"award-info":[{"award-number":["FKZ 01ER0828"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007421","name":"Li Ka Shing Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007421","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2018,7]]},"abstract":"Objective<\/jats:title>Uveitis is a visually debilitating disorder that affects up to 30% of children with the most common forms of juvenile idiopathic arthritis (JIA<\/jats:styled-content>). The disease mechanisms predisposing only a subgroup of children to uveitis are unknown. This study was undertaken to identify genetic susceptibility loci for uveitis in JIA<\/jats:styled-content>, using a genome\u2010wide association study in 522 children with JIA<\/jats:styled-content>.<\/jats:p><\/jats:sec>Methods<\/jats:title>Two cohorts of JIA<\/jats:styled-content> patients with ophthalmologic follow\u2010up data were genotyped. Data were then imputed using a genome\u2010wide imputation reference panel, and an HLA<\/jats:styled-content>\u2010specific reference panel was used for imputing amino acids and HLA<\/jats:styled-content> types in the major histocompatibility complex (MHC<\/jats:styled-content>). After imputation, genome\u2010wide and MHC<\/jats:styled-content>\u2010specific analyses were performed, and a reverse immunology approach was utilized to model antigen presentation at 13 common HLA<\/jats:styled-content>\u2013DR<\/jats:styled-content>\u03b21 alleles.<\/jats:p><\/jats:sec>Results<\/jats:title>Presence of the amino acid serine at position 11 (serine 11) in HLA<\/jats:styled-content>\u2013DR<\/jats:styled-content>\u03b21<\/jats:italic> was associated with an increased risk of uveitis in JIA<\/jats:styled-content> patients (odds ratio [OR<\/jats:styled-content>] 2.60, P<\/jats:italic> = 5.43 \u00d7 10\u221210<\/jats:sup>) and was specific to girls (P<\/jats:italic>females<\/jats:sub> = 7.61 \u00d7 10\u221210<\/jats:sup> versus P<\/jats:italic>males<\/jats:sub> = 0.18). Serine 11 resides in the YST<\/jats:styled-content> motif in the peptide\u2010binding groove of HLA<\/jats:styled-content>\u2013DR<\/jats:styled-content>\u03b21; all 3 amino acids in this motif are in perfect linkage disequilibrium and show identical association with disease. Quantitative prediction of binding affinity revealed that HLA<\/jats:styled-content>\u2013DR<\/jats:styled-content>\u03b21 alleles with the YST<\/jats:styled-content> motif could be distinguished on the basis of discernable peptide\u2010binding preferences.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>These findings highlight a genetically distinct, sexually dimorphic feature of JIA<\/jats:styled-content> with uveitis as compared to JIA<\/jats:styled-content> without uveitis. The association could be indicative of the potential involvement of antigen presentation by HLA<\/jats:styled-content>\u2013DR<\/jats:styled-content>\u03b21 in the development of uveitis in JIA<\/jats:styled-content>. The results of this study may advance our progress toward improved treatments for, and possible prevention of, the sight\u2010threatening complications of uveitis in children with JIA<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40484","type":"journal-article","created":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T12:41:19Z","timestamp":1520426479000},"page":"1155-1165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Identification of an Amino Acid Motif in HLA<\/scp>\u2013DR<\/scp>\u03b21 That Distinguishes Uveitis in Patients With Juvenile Idiopathic Arthritis"],"prefix":"10.1002","volume":"70","author":[{"given":"Anne\u2010Mieke J. W.","family":"Haasnoot","sequence":"first","affiliation":[{"name":"University Medical Center Utrecht, Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco W.","family":"Schilham","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Kamphuis","sequence":"additional","affiliation":[{"name":"Sophia Children's Hospital, Erasmus University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra C. 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