Reduction of the complement activation capacity of soluble IgG aggregates and immune complexes by IgM-rheumatoid factor

Abstract

The influence of IgM-rheumatoid factor (IgM-RF) on the activation of isolated C1 by soluble IgG aggregates (AIgG) and immune complexes was studied. IgM preparations obtained from the sera of four patients with seropositive rheumatoid arthritis markedly reduced the C1 activation capacity of AIgG, especially when large aggregates were tested. The results of parallel experiments with radiolabelled AIgG indicated that this inhibitory effect of IgM-RF was accompanied by a very large increase of the aggregate size. A comparable IgM preparation isolated from pooled normal human serum influenced neither the size nor the C1 activation capacity of AIgG. The inhibitory effect of IgM-RF on C1 activation was also demonstrated for soluble tetanus-anti-tetanus immune complexes. Thus, in spite of the established C activation ability of IgM-RF and the fact that, in general, larger IgG aggregates and immune complexes activate C1 more efficiently, cross-linking and size enlargement of soluble IgG complexes and aggregates by IgM-RF lead to a decrease of the C1 activation capacity. As a consequence, IgM-RF may reduce plasma complement activation by soluble IgG complexes in the circulation of patients with seropositive rheumatic diseases.