{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T07:35:02Z","timestamp":1785569702838,"version":"3.56.0"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2005,11,28]],"date-time":"2005-11-28T00:00:00Z","timestamp":1133136000000},"content-version":"vor","delay-in-days":8612,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[1982,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Measurement of serum rheumatoid factor (RF) by conventional methods in patients with rheumatoid arthritis (RA) has repeatedly identified a subpopulation of patients without detectable RF. Previous investigators have consistently confirmed the association of HLA\u2013DR4 with seropositive RA, but studies of seronegative RA have been limited and contradictory. We studied 140 randomly selected patients from Alabama, all of whom had either classic or definite RA, and we were able to obtain complete HLA typing for 110 of these individuals. Eighty were consistently seropositive (on at least 2 separate occasions) and 30 were consistently seronegative (on at least 3 separate determinations). There was no statistically significant difference between the seronegative RA patients and 123 control subjects in the distribution of DR antigens. In seropositive RA, there was a significant increase in DR4 (<jats:italic>P<\/jats:italic>&lt;0.001; relative risk = 8.02; attributable risk = 49.2%) and a significant decrease in DR3 (<jats:italic>P<\/jats:italic>&lt;0.001; relative risk = 0.14) and DR7 (0.01&gt;<jats:italic>P<\/jats:italic>&gt;0.001; relative risk = 0.33). The clinical data also distinguished between seropositive RA and seronegative RA; subcutaneous nodules (37.5%) and vasculitis (6.3%) were present only in seropositive RA. DR4 positivity did not correlate with any of the clinical variables measured in the seropositive RA group. In contrast, DR4 in the seronegative RA group was associated with more destructive disease. The data suggest that seronegative RA represents a disease entity clinically and immunogenetically distinct from seropositive RA. Moreover, our results indicate that DR4 may be a previously undisclosed marker for disease severity in seronegative RA.<\/jats:p>","DOI":"10.1002\/art.1780250503","type":"journal-article","created":{"date-parts":[[2007,2,14]],"date-time":"2007-02-14T20:02:32Z","timestamp":1171483352000},"page":"502-507","source":"Crossref","is-referenced-by-count":61,"title":["Seronegative rheumatoid arthritis."],"prefix":"10.1002","volume":"25","author":[{"given":"Graciela S.","family":"Alarc\u00f3N","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Koopman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald T.","family":"Acton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce O.","family":"Barger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,11,28]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.19.3.209"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-60-1-88"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0049-0172(76)90013-5"},{"key":"e_1_2_1_5_2","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0307-742X(21)00026-6","article-title":"Seronegative peripheral arthritis","volume":"3","author":"Milazzo SC","year":"1977","journal-title":"Clin Rheum Dis"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.36.4.365"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197804202981602"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.6148.1326"},{"key":"e_1_2_1_9_2","first-page":"1306","article-title":"HLA\u2013D and DR determinants in rheumatoid arthritis","volume":"11","author":"Jaraquemada O","year":"1979","journal-title":"Transplant Proc"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(79)91186-3"},{"key":"e_1_2_1_11_2","first-page":"9","article-title":"Rheumatoid arthritis and B lymphocyte alloantigen HLA\u2013DRw4","volume":"7","author":"Scherak O","year":"1980","journal-title":"J Rheumatol"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780230307"},{"key":"e_1_2_1_13_2","unstructured":"StastnyP:Rheumatoid arthritis. Joint report from the 8th Histocompatibility Workshop. Los Angeles 1980"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(195902)2:1<16::AID-ART1780020104>3.0.CO;2-9"},{"key":"e_1_2_1_15_2","first-page":"888","article-title":"The latex fixation test. I. Application to the serologic diagnosis of rheumatoid arthritis","volume":"21","author":"Singer JM","year":"1956","journal-title":"Am J Med"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1949.02900430001001"},{"key":"e_1_2_1_17_2","volume-title":"Roentgen Diagnosis of Rheumatoid Arthritis","author":"Berens DL","year":"1969"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780190518"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/69.2.103"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1979.tb00856.x"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.1955.tb01348.x"},{"key":"e_1_2_1_22_2","first-page":"242","article-title":"Attributable risk percent in casecontrol studies","volume":"25","author":"Cole P","year":"1971","journal-title":"Br J Preventive Soc Med"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780231102"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780240516"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780240623"},{"key":"e_1_2_1_26_2","first-page":"688","article-title":"Heterogeneity of HLA\u2013DRw4 in a Chippewa population (abstract)","volume":"23","author":"Harvey J","year":"1980","journal-title":"Arthritis Rheum"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1979.tb01137.x"},{"key":"e_1_2_1_28_2","first-page":"677","volume-title":"Textbook of Rheumatology","author":"Carson DA","year":"1981"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(79)91285-6"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(81)90846-9"},{"key":"e_1_2_1_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(80)91100-9"},{"key":"e_1_2_1_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/103.3.579"},{"key":"e_1_2_1_33_2","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1093\/oxfordjournals.bmb.a071513","article-title":"HLA genetic heterogeneity and diabetes mellitus","volume":"34","author":"Cudworth AG","year":"1978","journal-title":"Br Med Bull"},{"key":"e_1_2_1_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780200501"},{"key":"e_1_2_1_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(78)90280-5"},{"key":"e_1_2_1_36_2","first-page":"549","article-title":"HLA\u2013DRw4 and rheumatoid arthritis","volume":"1","author":"Husby G","year":"1979","journal-title":"Lancet"},{"key":"e_1_2_1_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(79)91395-3"},{"key":"e_1_2_1_38_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-93-4-551"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.1780250503","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.1780250503","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T18:49:44Z","timestamp":1700765384000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.1780250503"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1982,5]]},"references-count":37,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1982,5]]}},"alternative-id":["10.1002\/art.1780250503"],"URL":"https:\/\/doi.org\/10.1002\/art.1780250503","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[1982,5]]}}}