IgM in a human neuropathy related carbohydrate determinant in the m3 and to a ganglioside (monoclonal antibody/myelin proteins/plasma cell dyscrasia/demyelin

The IgM in three patients with paraprotein- emia and peripheral neuropathy was shown to bind to human myelin-associated glycoprotein (MAG) that had been purified to homogeneity by gel filtration on Sepharose CL-6B. The antigenic determinant reacting with the IgM from all three pa- tients was in the carbohydrate part of the MAG molecule. In addition, the IgM from the same three patients bound to a single ganglioside of human sciatic nerve. The results indicate that the IgM paraproteins in these patients react with a carbo- hydrate determinant that is shared between MAG and a pe- ripheral nerve ganglioside. Some patients producing large amounts of monoclonal IgM due to plasma cell dyscrasia have a demyelinating peripheral neuropathy (1). There is evidence to suggest that the neurop- athies are caused by binding of the IgM paraproteins to pe- ripheral nerve antigens (2-9), although this has not been es- tablished. Experiments in several laboratories have provided evidence that the monoclonal IgM in some of these patients binds to the myelin-associated glycoprotein (MAG) (10-14). In this paper, it is demonstrated that the monoclonal IgM antibodies in three neuropathy patients of this type bind to human MAG purified to homogeneity by the procedure rou- tinely used in our laboratory for chemical studies on this gly- coprotein (15). It is further shown that the antibodies are di- rected against determinants in the carbohydrate part of the MAG molecule. Experiments are also described, however, which indicate that the IgM antibodies produced by the same patients bind to a ganglioside of human sciatic nerve. The results indicate that there are at least two molecules in pe- ripheral nerve containing the carbohydrate antigen that re- acts with the paraproteins produced by these patients. If the monoclonal IgM causes the neuropathy in these patients, both MAG and the ganglioside are candidates to be involved in the dysimmune phenomena. Some of the results reported here have been described in abstract form (13, 16). MATERIALS AND METHODS