One hundred and forty-two patients with 'definite' or 'classical' rheumatoid arthritis (RA) were studied for the frequency and possible prognostic significance of HLA DR4. Of these, 122 were seropositive, while 20 were negative for rheumatoid factor (RF) in serum. The HLA antigen DR4 was significantly increased in the seropositive group (65%) as well as in the seronegative group (55%) in comparison with a frequency of 27% in 116 healthy controls. Among seropositive patients a higher frequency of DR4 was found in females (73%) than in males (50%), the difference being statistically significant (p less than 0.01). DR4 was more frequent among patients with a family history of RA (74%) than among patients without affected relatives (57%). DR4 appeared to be associated with an early onset of RA. No significant differences in general disease activity or functional capacity between DR4-positive and DR4-negative RA patients were found. Patients without the HLA antigen DR4 had a significantly (p less than 0.05) higher mean titre of RF than those with the antigen.
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