The myelin-associated glycoprotein (MAG) is localized in the periaxonal part of PNS and CNS myelin sheaths where it appears to be involved in glia-axon ineractions. The amount of MAG in Jimpy mice with a severe hypomyelination is reduced to 5% of the control level, but its apparent molecular weight is not higher than normal as had previously been described in Quaking and Grembler mice. Several types of monoclonal antibodies have now been identified that react with related carbohydrate epitopes in MAG and other glycoconjugates. These include: 1. several that were generated by MBDS in mice immunized with MAG; 2. HNK-1, that reacts with a subset of human lymphocytes; 3. 10C5, an antibody reacting with glycoproteins in melanoma, small cell lung carcinoma and other tumors of neuroectodermal origin; 4. L2, an antibody reacting with several proteins involved in cell-cell interactions including neural cell adhesion molecule (N-CAM); and 5. human monoclonal IgM in paraproteinemia associated with neuropathy. In addition to MAG, each of these antibodies reacts with glycolipids and 20 to 26 K dalton glycoproteins that are specific for the PNS. The principal glycolipid reacting with these antibodies is an unusual sulfated, glucoronic acid-containing sphingoglycolipid that had not previously been described. The carbohydrate epitopes in MAG and other glycoconjugates of nervous tissue that are shared with the immune system and various tumors of neuroectodermal origin may be relevant to demyelinating diseases. A number of patients with IgM paraproteinemia associated with neuropathy have been identified in which the IgM does not react with MAG but does react with other glycolipids, indicating that glycolipid antigens are frequent in neuropathy associated with IgM gammopathy. Relatively high levels of a proteolytic derivative of MAG, dMAG are present in all cerebrospinal fluids, but the amount does not correlate with active demyelination. A low level of anti-MAG antibodies was detected in the cerebrospinal fluid of multiple sclerosis patients.
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