Complement activation by 19S IgM rheumatoid factor: Relationship to disease activity in rheumatoid arthritis

19S IgM rheumatoid factor (RF) in rheumatoid arthritis (RA) are polyclonal auto-antibodies directed against the Fc piece of IgG. Rheumatoid patients with RF tend to have aggressive synovitis, nodules, and extraarticular manifestations. Alhough RF titer does not correlate with disease activity, RF activates complement (C) by the classical pathway. Thus, we postulated that selective stimulation of cell clones producing efficient C activating RF molecules might be associated with disease flares, independent of changes in serum RF concentration. To address the question, 42 patients with RA were evaluated prospectively. Serum RF cncentration was measured by radioimmunoassay (RIA) and C activating activity by hemolytic assay. We then calculated the mean hemolysis (MH) of sensitized sheep erythrocytes (SRC) produced/ml of RF serum (MH/ml) and MH/μg of RF as an expression of RF C activating properties (CAP). The following observations were made: (1) RF CAP varied among the patients studied; (2) RF CAP varied over time in individual patients; (3) RF CAP differences varied in both groups independently from RF concentration; (4) RF CAP correlated with both systemic and articular disease activity; and (5) total RF concentration correlated with articular findings and nodules but less well with systemic disease activity.