Anti-red blood cell (RBC) immunoglobulin G (IgG) autoantibodies are present in patients with warm autoimmune haemolytic anaemia (WAIHA), and, as natural autoantibodies, in healthy individuals. This study investigated whether the feature of polyreactivity discriminates disease-associated from natural anti-RBC IgG autoantibodies. The patterns of reactivity of puri®ed anti-RBC IgG eluted from the RBC of WAIHA patients and from the RBC of healthy individuals were analysed using quantitative immunoblotting on a panel of whole human tissue or bacterial cell extracts as antigen sources. In parallel, the reactivity patterns of IgG puri®ed from plasma were analysed. Anti-RBC IgG of WAIHA patients and of healthy individuals recognized a wide range of self-and nonself-antigens. The reactivity patterns of anti-RBC IgG were homogeneous among patients and controls, did not differ between patients and controls, and were similar to those of IgG puri®ed from plasma in the case of both patients and healthy individuals. The data demonstrate that the anti-RBC IgG autoantibodies of WAIHA patients share extensive similarity with those of healthy individuals. Polyreactivity is a common feature of both disease-associated and natural anti-RBC IgG autoantibodies.

Immunoglobulin preparations enriched with IgM and IgA are used in the therapy of severe bacterial infections and for the treatment of acute graft-versus-host disease, but not as yet, in the treatment of autoimmune diseases. We investigated the potential of an IgM- and IgA-enriched immunoglobulin preparation to neutralize activity autoantibodies from patients with autoimmune diseases. We demonstrate that Pentaglobin(R) was at least as effective as intravenous immunoglobulin (Sandoglobulin(R)) in inhibiting autoantibody activity. Each of the immunoglobulin isotypes present in Pentaglobin(R) may be responsible for the inhibitory effect. Pentaglobin(R) immobilized on an affinity matrix retained the disease associated autoantibodies and interacted with F(ab')2 fragments of IgG autoantibodies. Suppression of autoantibody activity is dependent, at least in part, on idiotypic interactions. The present findings provide a rationale for considering these preparations for the immunomodulation of autoimmune disease.