myelin-basic-protein and Waldenstrom-Macroglobulinemia

In a previously described case of Waldenstrom's Macroglobulinemia, complicated by polyneuropathy, the IgM/lambda monoclonal antibody (mAb) was highly reactive with myelin basic protein (MBP). Given our demonstration that V lambda x, 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 lambda x and this human IgM/lambda anti-MBP was investigated. We characterized the epitope specificity of the macroglobulinemia patient's MBP-reactive IgM/lambda 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 V lambda x as the secondary Ab. The patient's MBP-reactive IgM/lambda was recognized by Ab specific for V lambda x and, like murine mAb containing V lambda x 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 'V lambda x 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.

Topics: Animals; Autoantibodies; Encephalomyelitis, Autoimmune, Experimental; Enzyme-Linked Immunosorbent Assay; Humans; Immunodominant Epitopes; Immunoglobulin M; Macroglobulins; Multiple Sclerosis; Myelin Basic Protein; Peptide Fragments; Polyneuropathies; Rabbits; Waldenstrom Macroglobulinemia

We report on the case of a 70-year-old man with primary macroglobulinemia who showed cranial polyneuropathy and extensive radiculoneuropathy. His serum contained an IgM lambda monoclonal antibody which reacted with both a high molecular weight protein in grey matter and purified myelin basic protein (MBP) on immunoblotting. In an immunohistochemical study, strong immunoreactivity was detected only in the cytoplasm of neurons and weak immunoreactivity was detected in myelin. These findings suggest that this antibody may be related to the pathogenesis of neuronal damage in patients with macroglobulinemia.

Topics: Aged; Antibodies, Monoclonal; Antibody Specificity; Blotting, Western; Cytoplasm; Fatal Outcome; Humans; Immunoglobulin M; Immunohistochemistry; Male; Myelin Basic Protein; Neurons; Waldenstrom Macroglobulinemia

Sera of 23 patients with Waldenström's macroglobulinaemia and six monoclonal IgM paraproteins, which had been isolated from these sera, were examined for reactivity against peripheral nerve tissue. Of these 23 patients, 12 had clinical signs of peripheral polyneuropathy (PN). Using an indirect immunofluorescence method, all sera and monoclonal IgM preparations reacted with peripheral nerve structures, displaying a distinct granular fluorescence pattern with anti-IgM sera. The Waldenström sera reacted mainly with structures at the border of the myelin sheath, as well as between myelin and axon, and occasionally with the axon itself. There was no difference between sera of patients with PN and those without. Negative results were obtained in a complement fixation assay. Of the 23 sera, 15 reacted in an antibody-dependent lymphocyte-mediated cytotoxicity reaction (ADLC) with peripheral nerve myelin, and to a much lesser extent with myelin basic protein from CNS. Five of the six isolated monoclonal IgM preparations also gave positive ADLC reactions. These results constitute additional evidence for an immunological mechanism in the pathogenesis of PN in Waldenström's macroglobulinaemia.

Topics: Aged; Antibody-Dependent Cell Cytotoxicity; Complement Fixation Tests; Fluorescent Antibody Technique; Humans; Immunoglobulin M; Middle Aged; Myelin Basic Protein; Myelin Sheath; Peripheral Nerves; Polyneuropathies; Waldenstrom Macroglobulinemia