Altered control of self-reactive IgG by autologous IgM in patients with warm autoimmune hemolytic anemia

Warm autoimmune hemolytic anemia (WAIHA) is characterized by an accelerated clearance of red blood cells (RBCs) associated with the presence of anti-R BC immunoglobulin (Ig)G autoantibodies. In the present study, we analyzed t he self-reactive IgG and IgM antibody repertoires of patients with WAIHA us ing a technique of quantitative immunoblotting on a panel of whole tissue e xtracts as sources of self-antigens. Data were compared by means of multipa rametric statistical analysis. We demonstrate that self-reactive antibody r epertoires of IgG purified from plasma and of IgG purified from RBC eluates do not differ between healthy donors and patients with WAIHA, whereas auto reactive repertoires of IgM from patients exhibit broadly altered patterns of reactivity as compared with those of healthy controls. We further demons trate that IgG purified from eluates of RBCs of healthy donors induces aggl utination of RBCs in an indirect Coombs assay to a similar extent as IgG pu rified from eluates of RBCs of patients with WAIHA. The capability of IgG t o induce agglutination of RBCs is suppressed in unfractionated eluates of h ealthy donors' cells, whereas it is readily found in unfractionated eluates of patients' RBCs, IgM is an essential factor in controlling the ability o f IgG in unfractionated RBC eluates to induce agglutination of RBCs. These observations indicate that anti-RBC IgG autoantibodies of patients with WAI HA share extensive similarity with natural anti-RBC autoantibodies of healt hy donors and suggest that defective control of IgG autoreactivity by autol ogous IgM is an underlying mechanism for autoimmune hemolysis in WAIHA. (C) 2000 by The American Society of Hematology.