HLA typing was carried out in 132 patients with rheumatoid arthritis (RA) with long term follow up, and special attention was focused on rheumatoid factor negative patients. The patients were divided into four groups: 55 patients with a seropositive RA and a positive antiperinuclear factor (group A); 39 seropositive patients but a negative antiperinuclear factor (group B); 14 patients consistently seronegative for 3-28 years (mean 11.8 years) but positive for antiperinuclear factor (group C); patients consistently negative for 3-28 years (mean 11.8) and also negative for antiperinuclear factor (group D). The prevalence of HLA-DR4 was 31/55 (56%), 29/39 (74%), 10/14 (71%), and 9/24 (37%) for groups A, B, C, and D respectively, and in all groups was significantly higher than in 277 healthy controls (55/277, 20%). No significant difference was found between seropositive (groups A and B) and seronegative (groups C and D) patients, but groups A, B, and C had higher prevalences than group D. It is concluded that in seronegative RA HLA-DR4 is preferentially associated with the antiperinuclear factor positive group.
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