POOLED NORMAL HUMAN POLYSPECIFIC IGM CONTAINS NEUTRALIZING ANTIIDIOTYPES TO IGG AUTOANTIBODIES OF AUTOIMMUNE PATIENTS AND PROTECTS FROM EXPERIMENTAL AUTOIMMUNE-DISEASE

Normal human serum contains IgM antibodies that regulate the natural a utoantibody activity of IgG in autologous serum. In the present study, we show that pooled normal human IgM (IVIgM) purified from plasma of more than 2,500 healthy donors and processed in a similar fashion to t hat of therapeutic preparations of pooled normal human IgG (IVIg) supp resses activity of IgG autoantibodies purified from the serum of patie nts with autoimmune diseases in vitro. The inhibitory effect of IVIgM was greater or equivalent to that of IVIg on a molar basis. We show th at IVIgM contains antiidiotypic antibodies directed against idiotypic determinants of autoantibodies, in particular by showing that Sepharos e-bound IVIgM selectively retained F(ab')(2) fragments of IgG autoanti bodies. The infusion of (Lewis x Brown-Norway) F1 rats with IVIgM prot ected the animals against experimental autoimmune uveitis induced by i mmunization with the soluble retinal S antigen, as evidenced by clinic al scoring and histopathological analysis. The present findings provid e a rationale for considering pooled IgM for immunomodulation of autoi mmune disease. (C) 1997 by The American Society of Hematology.