IgM monoclonal gammopathy is frequently associated with peripheral neuropathy. In approximately 50% of the patients, the neuropathy may be caused by IgM M-proteins that bind to a carbohydrate determinant shared by the myelin associated glycoprotein (MAG), as well as by several other glycoproteins and two glycolipids in peripheral nerve. The reason for the frequent occurrence of IgM M-proteins with the same specificity is unknown, but the monoclonal gammopathy could result from an abnormality linked to the expression of an immunoglobulin heavy chain variable region (VH) gene that encodes for antibodies with that particular specificity. To determine whether anti-MAG M-proteins from different patients are encoded by the same VH genes, M-protein secreting hybridomas will be generated from patients' B-cells, and the VH regions that encode the M-proteins will be cloned from genomic DNA libraries constructed from the hybridoma cells. The VH genes will then be sequenced and compared for homology. If the same VH genes are utilized to encode for anti-MAG M- proteins in different patients, it would suggest that an abnormality linked to the expression of these genes may be responsible for the development of the monoclonal gammopathy. Otherwise, other mechanisms, possible dependent on the antigenic specificity of the M-proteins, might be responsible. Depending on the results of these experiments, future studies could be designed to further examine the mechanisms responsible for the development of monoclonal gammopathies.
