Anti-myelin associated glycoprotein (MAG) IgM antibodies are now recognized as a treatable cause of acquired peripheral neuropathy in adulthood. The antibodies react with a carbohydrate epitope that is highly concentrated in peripheral nerve myelin and is shared by the myelin associated glycoprotein (MAG) and several other glycoconjugates in peripheral nerve. Increased titers of monoclonal or polyclonal anti-MAG antibodies are invariably associated with a demyelinating neuropathy, but low antibody titers are frequently found in normal individuals, a nd B-cells capable of secreting the antibodies are present at birth. The reason for the occurrence of anti-MAG antibodies and for their increase in patients with peripheral neuropathy is unknown.
The aim of the proposed project is to investigate the molecular mechanisms responsible for the frequent occurrence of anti=-MAG antibodies in normal individuals, the reasons for their increase in patients with peripheral neuropathy, and the structural basis for their binding activity. Specifically, the immunoglobulin variable region genes encoding anti-MAG antibodies in different patients will be cloned from hybridoma lines generated from the patients' lymphocytes, and their nucleotide sequences compared to determine whether the different antibodies are encoded by the same or similar variable region genes. The expressed variable regions will then be compared to their germline sequences, cloned from fibroblast lines of the same patients, in order to determine whether they are encoded by germline genes with little or no somatic mutations, or whether they evolve by somatic mutations as occurs in a T-cell dependent, antigen driven immune response. In addition, the deduced amino acid sequences of the variable regions encoding the different anti-MAG antibodies will be compared to determine whether there are common sequences present in their complementary determining regions which might be important for their binding activity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS025187-05
Application #
3410391
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1987-07-01
Project End
1994-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
5
Fiscal Year
1992
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