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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS025187-01
Application #
3410385
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1987-07-01
Project End
1990-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027