{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:23:23Z","timestamp":1789421003679,"version":"build-2803163510"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,3,27]],"date-time":"2015-03-27T00:00:00Z","timestamp":1427414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"BTCURE"},{"name":"Masterswitch"},{"name":"Netherlands Organization for Scientific Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>For decades it has been known that the HLA\u2013DRB1 shared epitope (SE) alleles are associated with an increased risk of development and progression of rheumatoid arthritis (RA). Recently, the following variations in the peptide\u2010binding grooves of HLA molecules that predispose to RA development have been identified: Val and Leu at HLA\u2013DRB1 position 11, Asp at HLA\u2013B position 9, and Phe at HLA\u2013DPB1 position 9. This study was undertaken to investigate whether these variants are also associated with radiographic progression in RA, independent of SE and anti\u2013citrullinated protein antibody (ACPA) status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 4,911 radiograph sets from 1,878 RA patients included in the Leiden Early Arthritis Clinic (The Netherlands), Ume\u00e5 (Sweden), Hospital Clinico San Carlos\u2013Rheumatoid Arthritis (Spain), and National Data Bank for Rheumatic Diseases (US) cohorts were studied. HLA was imputed using single\u2010nucleotide polymorphism data from an Immunochip, and the amino acids listed above were tested in relation to radiographic progression per cohort using an additive model. Results from the 4 cohorts were combined in inverse\u2010variance weighted meta\u2010analyses using a fixed\u2010effects model. Analyses were conditioned on SE and ACPA status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Val and Leu at HLA\u2013DRB1 position 11 were associated with more radiographic progression (meta\u2010analysis <jats:italic>P<\/jats:italic> = 5.11 \u00d7 10<jats:sup>\u22127<\/jats:sup>); this effect was independent of SE status (meta\u2010analysis <jats:italic>P<\/jats:italic> = 0.022) but not independent of ACPA status. Phe at HLA\u2013DPB1 position 9 was associated with more severe radiographic progression (meta\u2010analysis <jats:italic>P<\/jats:italic> = 0.024), though not independent of SE status. Asp at HLA\u2013B position 9 was not associated with radiographic progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Val and Leu at HLA\u2013DRB1 position 11 conferred a risk of a higher rate of radiographic progression independent of SE status but not independent of ACPA status. These findings support the relevance of these amino acids at position 11.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39018","type":"journal-article","created":{"date-parts":[[2015,1,7]],"date-time":"2015-01-07T15:02:52Z","timestamp":1420642972000},"page":"877-886","source":"Crossref","is-referenced-by-count":21,"title":["Association of Valine and Leucine at HLA\u2013DRB1 Position 11 With Radiographic Progression in Rheumatoid Arthritis, Independent of the Shared Epitope Alleles but Not Independent of Anti\u2013Citrullinated Protein Antibodies"],"prefix":"10.1002","volume":"67","author":[{"given":"H. W.","family":"van Steenbergen","sequence":"first","affiliation":[{"name":"Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Raychaudhuri","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Harvard Medical School, and Partners HealthCare Center for Personalized Genetic Medicine, Boston, Massachusetts, Broad Institute of Harvard and MIT Cambridge Massachusetts"},{"name":"University of Manchester and Manchester Academic Health Sciences Centre Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Rodr\u00edguez\u2010Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"San Carlos Clinical Hospital Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Rantap\u00e4\u00e4\u2010Dahlqvist","sequence":"additional","affiliation":[{"name":"University Hospital Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Berglin","sequence":"additional","affiliation":[{"name":"University Hospital Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. E. M.","family":"Toes","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. W. J.","family":"Huizinga","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Fern\u00e1ndez\u2010Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"San Carlos Clinical Hospital Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. K.","family":"Gregersen","sequence":"additional","affiliation":[{"name":"Feinstein Institute for Medical Research and North Shore\u2013LIJ Health System Manhasset New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. H. M.","family":"van der Helm\u2010van Mil","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,3,27]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-203375"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21272"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27366"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.62.7.611"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108382"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780301102"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21385"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21302"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/342407"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1076"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.02.013"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.160.6.1752"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830220612"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21739"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keq230"},{"key":"e_1_2_6_18_1","first-page":"1002","article-title":"Antibodies against mutated citrullinated vimentin are a better predictor of disease activity at 24 months in early rheumatoid arthritis than antibodies against cyclic citrullinated peptides","volume":"35","author":"Innala L","year":"2008","journal-title":"J Rheumatol"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.3109\/03009742.2013.785590"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keq155"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064683"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.998"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2008.00997.x"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200103)44:3<535::AID-ANR101>3.0.CO;2-Z"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10210"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.37938"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.3109\/03009742.2012.728618"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131241"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.39018","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.39018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T12:57:13Z","timestamp":1759928233000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.39018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,27]]},"references-count":27,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2015,4]]}},"alternative-id":["10.1002\/art.39018"],"URL":"https:\/\/doi.org\/10.1002\/art.39018","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,27]]}}}