{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:28:44Z","timestamp":1780471724110,"version":"3.54.1"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,2,28]],"date-time":"2012-02-28T00:00:00Z","timestamp":1330387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["K23-AR-50177"],"award-info":[{"award-number":["K23-AR-50177"]}]},{"name":"NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["RC1-AR-058587"],"award-info":[{"award-number":["RC1-AR-058587"]}]},{"name":"NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["P30-AR-473639"],"award-info":[{"award-number":["P30-AR-473639"]}]},{"name":"NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["1-R01-AR-049762-01A2"],"award-info":[{"award-number":["1-R01-AR-049762-01A2"]}]},{"name":"NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["R21-AI-075254"],"award-info":[{"award-number":["R21-AI-075254"]}]},{"name":"NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["P01-AR-048929"],"award-info":[{"award-number":["P01-AR-048929"]}]},{"name":"NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["N01-AR-42272"],"award-info":[{"award-number":["N01-AR-42272"]}]},{"DOI":"10.13039\/100000980","name":"Arthritis Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000980","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Val A. Browning Charitable Foundation"},{"name":"Primary Children's Medical Center Foundation, Salt Lake City, Utah"},{"name":"Rooms To Go Children's Fund"},{"DOI":"10.13039\/100001068","name":"Dana Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001068","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Associations between shared epitope (SE)\u2013encoding <jats:italic>HLA\u2013DRB1<\/jats:italic> alleles and rheumatoid arthritis (RA) are well established. However, only a limited number of studies have investigated these alleles in patients with childhood\u2010onset RA, which is defined as rheumatoid factor\u2013 and\/or anti\u2013citrullinated protein antibody\u2013positive juvenile idiopathic arthritis. The aims of this study were to investigate the largest cohort of patients with childhood\u2010onset RA for association with SE alleles and to determine whether there is a hierarchy of risk based on the amino acid sequence of the SE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>High\u2010resolution <jats:italic>HLA\u2013DRB1<\/jats:italic> genotypes were obtained for 204 patients with childhood\u2010onset RA and 373 healthy control subjects. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for different SE\u2010encoding <jats:italic>HLA\u2013DRB1<\/jats:italic> alleles. In addition, genotype ORs were calculated for combinations of SE alleles classified into S<jats:sub>2<\/jats:sub>, S<jats:sub>3P<\/jats:sub>, or L alleles, based on amino acid sequences in position 70\u201374 of the DR\u03b21 chain, as proposed by Tezenas du Montcel et al.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We confirmed associations between <jats:italic>HLA\u2013DRB1<\/jats:italic> SE alleles and childhood\u2010onset RA (76% of patients carried 1 or 2 SE alleles compared with 46% of control subjects; OR 3.81, 95% CI 2.4\u20136.0, <jats:italic>P<\/jats:italic> &lt; 1 \u00d7 10<jats:sup>\u22127<\/jats:sup>). We also observed associations between individual SE alleles (<jats:italic>HLA\u2013DRB1<\/jats:italic>*0101, *0401, *0404, *0405, *0408, and *1001) and childhood\u2010onset RA. Genotype\u2010specific risk estimates suggested a hierarchy of risk, with the highest risk among individuals heterozygous for S<jats:sub>2<\/jats:sub>\/S<jats:sub>3P<\/jats:sub> (OR 22.3, 95% CI 9.9\u201350.5, <jats:italic>P<\/jats:italic> &lt; 0.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We confirm the association between SE\u2010encoding <jats:italic>HLA\u2013DRB1<\/jats:italic> alleles and susceptibility to childhood\u2010onset RA. The excess risk conferred by carriage of the combination of S<jats:sub>2<\/jats:sub> and S<jats:sub>3P<\/jats:sub> risk alleles suggests that children with DR\u03b21 chains containing the KRAA and QRRAA or RRRAA sequences are especially susceptible to RA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.33376","type":"journal-article","created":{"date-parts":[[2011,9,28]],"date-time":"2011-09-28T02:33:36Z","timestamp":1317177216000},"page":"925-930","source":"Crossref","is-referenced-by-count":43,"title":["Hierarchy of risk of childhood\u2010onset rheumatoid arthritis conferred by HLA\u2013DRB1 alleles encoding the shared epitope"],"prefix":"10.1002","volume":"64","author":[{"given":"Sampath","family":"Prahalad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan D.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen N.","family":"Conneely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxuan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Traci","family":"Leong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Prozonic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton R.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori A.","family":"Ponder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila T.","family":"Angeles\u2010Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry B.","family":"Vogler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Kennedy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol A.","family":"Wallace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol A.","family":"Wise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilynn","family":"Punaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Reed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane L.","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth 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N.","family":"Glass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,2,28]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.582"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780301102"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000024"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20989"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1949"},{"key":"e_1_2_6_7_2","first-page":"1611","article-title":"DNA analysis of HLA\u2010DR, DQ, and DP alleles in children with polyarticular juvenile rheumatoid arthritis","volume":"19","author":"Barron KS","year":"1992","journal-title":"J 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susceptibility to rheumatoid arthritis","volume":"51","author":"Wordsworth P","year":"1992","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23166"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08689"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.489"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21575"}],"container-title":["Arthritis &amp; 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