AbstractImmunologic functions of peripheral blood mononuclear cells were studied in rheumatoid arthritis (RA) patients treated with methotrexate (MTX). Spontaneous IgM rheumatoid factor (IgM‐RF) synthesis by unstimulated cultured blood mononuclear cells was seen in only 3 of 18 MTX‐treated patients, compared with 31 of 54 RA patients who were not receiving long‐acting drugs. Total IgM production by unstimulated cultured mononuclear cells, pokeweed mitogen‐induced antibody synthesis, and plasma levels of IgM‐RF were also lower in MTX‐treated patients than in other RA patients. The numbers of circulating B cells, T4 and T8 cells, the T4:T8 cell ratio, and mitogen‐induced proliferation indices were similar in MTX‐treated and non‐MTX‐treated patients. Eleven additional patients were studied prospectively after initiation of MTX therapy. All showed significant decreases in spontaneous IgM‐RF synthesis, with declining IgM‐RF:IgM ratios, including all of the 9 who were studied during the first 24 hours of treatment. The results indicate that MTX has rapid effects on IgM‐RF synthesis, and this action might be associated with its t
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