{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T16:36:06Z","timestamp":1771000566368,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2005,12,9]],"date-time":"2005-12-09T00:00:00Z","timestamp":1134086400000},"content-version":"vor","delay-in-days":5913,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[1989,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In response to the continuing debate as to whether seronegative rheumatoid arthritis (RA) and seropositive RA are part of the same disease spectrum or are distinct disorders, we evaluated 720 patients with definite and classic RA, of whom 53 subjects had definite persistently seronegative destructive disease. For all but 1 seronegative RA patient, a seropositive RA case control was identified and matched for age, disease duration, degree of destruction on hand radiographs, and disease\u2010modifying drug therapy. DR typing was undertaken on these 105 patients, together with scoring of hand radiographs. The frequency of DR4 was 69% in seropositive RA patients and 60% in seronegative RA patients (<jats:italic>P<\/jats:italic> = 0.22), versus 36% in 318 healthy controls (<jats:italic>P<\/jats:italic> = 0.008 and <jats:italic>P<\/jats:italic> = 0.007 versus seropositive and seronegative RA, respectively). Patients were matched and rematched with different controls in a series of subanalyses in order to make comparisons of hand radiograph scores. We found that HLA\u2013DR4 was associated with destructive RA in both seropositive and seronegative RA patients. In general, DR4+ patients had more severe disease by radiologic criteria than did DR4\u2013 patients. Thus, HLA\u2013DR4 may be an additive factor to the serologic status and may be more closely related to disease severity than to disease susceptibility.<\/jats:p>","DOI":"10.1002\/anr.1780321006","type":"journal-article","created":{"date-parts":[[2007,2,14]],"date-time":"2007-02-14T22:40:18Z","timestamp":1171492818000},"page":"1221-1225","source":"Crossref","is-referenced-by-count":65,"title":["Destructive arthritis, rheumatoid factor, and HLA\u2013DR4. Susceptibility versus severity, a case\u2013control study"],"prefix":"10.1002","volume":"32","author":[{"given":"Andrei","family":"Calin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith","family":"Elswood","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter T.","family":"Klouda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,12,14]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(81)90846-9"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.42.6.605"},{"key":"e_1_2_1_4_2","first-page":"6","article-title":"Seronegative rheumatoid arthritis and HLA\u2010DR4: proposal for criteria","volume":"14","author":"Gran JT","year":"1987","journal-title":"J Rheumatol"},{"key":"e_1_2_1_5_2","first-page":"4","article-title":"Rheumatoid factor negative (seronegative) rheumatoid arthritis: evolving clinical classification and immunogenetic associations","volume":"15","author":"Masi AT","year":"1988","journal-title":"J Rheumatol"},{"key":"e_1_2_1_6_2","first-page":"1","article-title":"Immunogenetics of rheumatoid arthritis (editorial)","volume":"15","author":"Woodrow JC","year":"1988","journal-title":"J Rheumatol"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.22.6962"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.8.2642"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111413"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(86)92614-0"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00915418"},{"key":"e_1_2_1_12_2","volume-title":"Definition of MCI, a novel HLA determinant associated with DR1 and DR4, Histocompatibility Testing","author":"Duquesnoy RJ","year":"1984"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/317359a0"},{"key":"e_1_2_1_14_2","first-page":"29","article-title":"Genetic heterogeneity of rheumatoid arthritis","volume":"4","author":"De Jongh BM","year":"1986","journal-title":"Dis Markers"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00541511"},{"key":"e_1_2_1_16_2","first-page":"9","article-title":"Estudios de los antigenos HLA\u2010DR en la artritis reumatoidea","volume":"9","author":"Nunez\u2010Roldan A","year":"1982","journal-title":"Rev Esp Reum"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.283.6302.1287"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.41.4.403"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1986.tb00454.x"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00541336"},{"key":"e_1_2_1_21_2","first-page":"51","article-title":"Association between DR antigens, rheumatoid arthritis with and without extraarticular features and SLE in northern Italy","volume":"15","author":"Ferraccioli GF","year":"1988","journal-title":"J Rheumatol"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(88)90422-6"},{"key":"e_1_2_1_23_2","first-page":"175","article-title":"1958 revision of diagnostic criteria for rheumatoid arthritis","volume":"9","author":"Ropes MW","year":"1958","journal-title":"Bull Rheum Dis"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI109265"},{"key":"e_1_2_1_25_2","first-page":"43","article-title":"HLA and rheumatoid arthritis: susceptibility or severity","volume":"4","author":"Jaraquemada D","year":"1986","journal-title":"Dis Markers"},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.47.8.648"},{"key":"e_1_2_1_27_2","first-page":"121","article-title":"HLA associations are with severe rheumatoid arthritis","volume":"4","author":"Walker DJ","year":"1986","journal-title":"Dis Markers"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/27.2.102"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.46.3.184"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.44.1.39"},{"key":"e_1_2_1_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780301102"},{"key":"e_1_2_1_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310111"}],"container-title":["Arthritis &amp; 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