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

In a previously described case of Waldenstrom's Macroglobulinemia, complica ted by polyneuropathy, the IgM/lambda monoclonal antibody (mAb) was highly reactive with myelin basic protein (MBP). Given our demonstration that V la mbdax, a recently described murine lambda 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 V lambdax and this human IgM/lambda an ti-MBP was investigated. We characterized the epitope specificity of the ma croglobulinemia patients MBP-reactive IgM/lambda using indirect ELISA proce dures with MBP. a citrullinated isomer of MBP termed C8, or peptide fragmen ts of MBP as the coating antigens and monospecific Ab to V lambdax as the s econdary Ab. The patient's MBP-reactive IgM/lambda was recognized by Ab spe cific for V lambdax and, like murine mAb containing V lambdax bound human M BP 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 macroglob ulin and perhaps certain other human Ab with a 'V lambdax idiotype' bind to MBP peptide residues 84-96, an immunodominant peptide in multiple sclerosi s patients. Such binding may be involved in the pathogenesis of neural dama ge in patients with neuroimmunologic disorders related to plasma cell dyscr asias or autoimmunity. (C) 2001 Elsevier Science B.V. All rights reserved.