Monoclonal anti-DNA IgM kappa in neuropathy binds to myelin and to a conformational epitope formed by phosphatidic acid and gangliosides.

Abstract

Anti-DNA antibodies that cross-react with phosphorylated epitopes of other cellular constituents may be involved in the pathogenesis of autoimmune disease. An IgM monoclonal antibody from a patient with chronic lymphocytic leukemia (CLL) and neuropathy bound to denatured DNA and immunostained myelin in peripheral nerve and spinal cord. The monoclonal IgM bound to ELISA microwells coated with a mixture of phosphatidic acid and gangliosides at serum dilutions of up to 1/100,000, but binding to phosphatidic acid alone was observed at dilutions of less than 1/100 only, and there was no binding to gangliosides alone. Incubation with micelles containing phosphatidic acid and gangliosides selectively absorbed the monoclonal IgM and inhibited its binding to denatured DNA and to myelin. These observations suggest that autoantibodies may bind to conformational epitopes formed by two separate molecules, and that autoantibodies that cross-react with phosphorylated epitopes in DNA and neural tissue could be involved in autoimmune neurologic diseases.