An IgM anti-MBP Ab in a case of Waldenstrom’s macroglobulinemia with polyneuropathy expressing an idiotype reactive with an MBP epitope immunodominant in MS and EAE

Abstract

In a previously described case of Waldenstrom’s Macroglobulinemia, complicated by polyneuropathy, the IgM/λ monoclonal antibody (mAb) was highly reactive with myelin basic protein (MBP). Given our demonstration that Vλx, a recently described murine λ variable region gene product, can itself bind MBP as well as confer MBP reactivity to an Ab, the possibility of a shared idiotypy between murine Vλx and this human IgM/λ anti-MBP was investigated. We characterized the epitope specificity of the macroglobulinemia patient’s MBP-reactive IgM/λ using indirect ELISA procedures with MBP, a citrullinated isomer of MBP termed C8, or peptide fragments of MBP as the coating antigens and monospecific Ab to Vλx as the secondary Ab. The patient’s MBP-reactive IgM/λ was recognized by Ab specific for Vλx and, like murine mAb containing Vλx bound human MBP but not MBP-C8 nor other common autoantigens such as DNA, thyroglobulin, or actin. The anti-MBP reactivity was selective for MBP peptide 90–170 and preferentially recognized MBP peptide 84–96. Thus, the patient’s macroglobulin and perhaps certain other human Ab with a ‘Vλx idiotype’ bind to MBP peptide residues 84–96, an immunodominant peptide in multiple sclerosis patients. Such binding may be involved in the pathogenesis of neural damage in patients with neuroimmunologic disorders related to plasma cell dyscrasias or autoimmunity.