{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:41:09Z","timestamp":1790804469985,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2016,10,6]],"date-time":"2016-10-06T00:00:00Z","timestamp":1475712000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["5 R01AI041721\u201012"],"award-info":[{"award-number":["5 R01AI041721\u201012"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["UL1 RR025014"],"award-info":[{"award-number":["UL1 RR025014"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Systemic sclerosis (SSc) is a rare disease that is particularly uncommon in children. Specific HLA alleles have been associated with SSc in adults. This study was undertaken to investigate HLA class II alleles in juvenile\u2010onset SSc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>DRB1, DQA1, and DQB1 alleles were determined by DNA\u2010based HLA typing. Analyses were conducted comparing Caucasian patients with juvenile\u2010onset SSc (n\u2009=\u200976) to healthy Caucasian controls (n\u2009=\u2009581).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Initial analyses focused on HLA class II associations previously reported in adult Caucasian patients with SSc. The frequency of DRB1*11 was not significantly increased in juvenile\u2010onset SSc (22.4% of patients with juvenile\u2010onset SSc versus 17.6% of controls; odds ratio [OR] 1.35, <jats:italic>P<\/jats:italic>\u2009=\u20090.34), nor were the specific DRB1*11:01 or *11:04 alleles. DQA1*05, a risk factor previously identified in adult men with SSc, was increased in patients with juvenile\u2010onset SSc versus controls (57.9% versus 44.1%; OR 1.76, <jats:italic>P<\/jats:italic>\u2009=\u20090.027), as was DRB1*03 (34.2% versus 22.5%; OR 1.79, <jats:italic>P<\/jats:italic>\u2009= 0.031). Secondary analyses of all DRB1 allele groups revealed an association with DRB1*10 (10.5% of patients with juvenile\u2010onset SSc versus 1.5% of controls; OR 7.48, <jats:italic>P<\/jats:italic>\u2009=\u20090.0002). As this is a new observation, correction was made for multiple comparisons of 13 different DRB1 allele groups; results nevertheless remained significant (<jats:italic>P<\/jats:italic>\u2009=\u20090.003). Also, a lower frequency of DRB1*01 was observed in patients with juvenile\u2010onset SSc who were younger at disease onset (OR 0.06, <jats:italic>P<\/jats:italic>\u2009=\u20090.01) and in those with antibodies to topoisomerase (OR 0.14, <jats:italic>P<\/jats:italic>\u2009=\u20090.024).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Associations of HLA alleles with juvenile\u2010onset SSc differed from associations with SSc in women, but were similar to associations with SSc in men. Additionally, a novel association with DRB1*10 was observed in children. The greatest proportion of genetic risk of SSc is contributed by the HLA complex, and the current study reveals the importance of the association of HLA class II genes in juvenile\u2010onset SSc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39765","type":"journal-article","created":{"date-parts":[[2016,5,24]],"date-time":"2016-05-24T06:49:10Z","timestamp":1464072550000},"page":"2772-2777","source":"Crossref","is-referenced-by-count":20,"title":["Brief Report: HLA\u2013DRB1, DQA1, and DQB1 in Juvenile\u2010Onset Systemic Sclerosis"],"prefix":"10.1002","volume":"68","author":[{"given":"Anne M.","family":"Stevens","sequence":"first","affiliation":[{"name":"Seattle Children's Research Institute and University of Washington Seattle"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami B.","family":"Kanaan","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn S.","family":"Torok","sequence":"additional","affiliation":[{"name":"University of Pittsburgh and Children's Hospital of the University of Pittsburgh Medical Center Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Medsger","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen D.","family":"Mayes","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Reveille","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Klein\u2010Gitelman","sequence":"additional","affiliation":[{"name":"Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann M.","family":"Reed","sequence":"additional","affiliation":[{"name":"Duke University School of Medicine Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzielan","family":"Lee","sequence":"additional","affiliation":[{"name":"Stanford University, Stanford, California and Lucile Packard Children's Hospital Palo Alto California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne C.","family":"Li","sequence":"additional","affiliation":[{"name":"Hackensack University Medical Center Hackensack New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gretchen","family":"Henstorf","sequence":"additional","affiliation":[{"name":"Seattle Children's Research Institute Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Luu","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa","family":"Aydelotte","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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