Autoantibody activity in Waldenstrom's macroglobulinemia

Some monoclonal proteins from patients with Waldenstrom's macroglobulinemia (WM) or immunoglobulin (Ig) M monoclonal gammopathy of undetermined significance possess antigen-binding activity directed to autogenous or foreign antigens. These monoclonal IgM autoantibodies include cold agglutinins, mixed cryoglobulins, and antineural components. Because of the antigenantibody interaction, patients with these autoimmune syndromes often present with hemolytic anemia, mixed cryoglobulinemia, or peripheral neuropathy, respectively, at an earlier stage than patients with typical WM who do not have evident antibody activity. The presence of monoclonal macroglobulin autoreactive antibodies thus influences clinical presentation and natural history. Monoclonal IgM antibodies display polyreactivity to antigens of microbial origin in addition to autogenous antigens and may arise through T-independent as well as T-dependent pathways. Waldenstrom proteins with antibody activity appear to provide a link between autoimmunity, infection, and lymphoproliferative disease. Study of the antigens reacting with monoclonal IgMs may provide further insight into the pathogenesis of WM.