Beneficial Effect of a Human Monoclonal IgM Cryoglobulin on the Autoimmune Disease of New Zealand Black Mice

Abstract

NZB mice spontaneously develop an autoimmune disease characterized by autoimmune hemolytic anemia, thymic atrophy, lymphoid hyperplasia, and hypergammaglobulinemia. The aim of this study was to examine the hypothesis that cryoglobulins may have an immunoregulatory effect on the autoimmune process. The effect of human monoclonal IgM cryoglobulin preparations (including Cryo13, Cryo14, and Cryo16) isolated from the serum of patients with Waldenström's macroglobulinemia on the autoimmune disease of NZB mice was therefore studied. The effect of cryoglobulin preparations was evaluated on several disease parameters, i.e., survival, severity of anemia, and serum IgM and IgG levels (hypergammaglobulinemia). We found that immunization of NZB mice with Cryo13 at 3 months of age delayed the course of the disease, whereas Cryo14 and Cryo16 were ineffective. Furthermore, the effect of Cryo13 was long lasting. On the other hand, Cryo13 was able to react with 8 of 32 mouse monoclonal natural IgM autoantibodies. In contrast, Cryo14 was able to bind only 2 and Cryo16 none of these mouse monoclonal IgM antibodies. These results indicate that, in this model of autoimmune pathology, the beneficial effect of Cryo13 is mediated by its idiotypic interaction with the murine natural autoantibody network.