g(m2)-ganglioside and Paraproteinemias

Antibodies against several neural antigens have been associated with different chronic immune-mediated neuropathies but their practical clinical relevance remains unclear. To determine the possible diagnostic usefulness of these antibodies we reviewed the clinical correlate of IgM antibodies to the myelin-associated glycoprotein (MAG), sulfatide, the gangliosides GM1, GM2, GD1a and GD1b in 539 consecutive patients examined for neuropathy or related diseases in our Neuropathy Clinics and tested for these antibodies in our laboratory since 1985. 302 patients (56%) had an established diagnosis of definite or possible chronic immune-mediated neuropathy while 237 had a neuropathy of non-immune-mediated origin or of unknown aetiology or a closely related disease. Antibodies to one or more antigen were more frequent (chi(2)=63.32; p<0.00001) in patients with chronic immune-mediated neuropathy (37.7%) than with other neuropathy or related diseases (7.2%) and their presence was associated in 87% of the patients with an immune-mediated neuropathy, incrementing by 31% the probability of having this form. Testing for MAG permitted to identify 24.8% of patients with an immune-mediated neuropathy, GM1 an additional 9.9%, while GM2, GD1b, GD1a and sulfatide altogether an additional 3% of the patients. Concerning clinical correlations, all 75 patients with anti-MAG IgM had neuropathy and IgM monoclonal gammopathy (PN+IgM) with a positive predictive value for this neuropathy of 100%. A similarly high predictive value for neuropathy (91.4%) was observed among 269 patients with IgM monoclonal gammopathy including 103 patients without neuropathy. Anti-sulfatide IgM, though rare, were also significantly and constantly associated with PN+IgM and permitted to identify few patients not bearing anti-MAG IgM. Anti-GM1 IgM were significantly associated with multifocal motor neuropathy (MMN) (29.2%) but where also found in a few patients with other immune or non-immune neuropathies or related diseases with a positive predictive value for MMN of 25.5%. Anti-GM2 IgM were also significantly associated with MMN and increased the sensitivity (36.2%) for MMN obtained with anti-GM1 IgM only, without affecting its specificity and positive predictive value. Anti-GD1a, GD1b, though not significantly more frequent in patients with immune-mediated neuropathy, were associated in 80 to 100% of patients with these neuropathies. In conclusion anti-neural IgM antibodies may help in identifying patie

Topics: Antibody Specificity; Autoimmune Diseases of the Nervous System; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; G(M2) Ganglioside; Gangliosides; Humans; Immunoblotting; Immunoglobulin M; Myelin-Associated Glycoprotein; Paraproteinemias; Retrospective Studies; Sulfoglycosphingolipids

It was previously reported that monoclonal IgM from two patients with gammopathy and neuropathy showed similar specificity by reacting with the same group of unidentified minor components in the ganglioside fractions of human nervous tissues (Ilyas, A. A., Quarles, R. H., Dalakas, M. C., and Brady, R. O. (1985) Proc. Natl. Acad. Sci. U. S. A. 82, 6697-6700). Enzymatic degradation, ion-exchange chromatography, and immunostaining of purified ganglioside standards on thin-layer chromatograms have now revealed that the antigenic glycolipids recognized by the IgM from these patients are gangliosides GalNAc beta 1-4Gal(3-2 alpha NeuAc)beta 1-4Glc beta 1-1Cer(GM2), GalNAc beta 1-4Gal(3-2 alpha NeuAc)beta 1-3GalNAc beta 1-4Gal beta 1-4Glc beta 1-1Cer (IV4GalNAcGM1b), and GalNAc beta 1-4Gal(3-2 alpha NeuAc)beta 1-3GalNAc beta 1-4 beta Gal(3-2 alpha NeuAc)beta 1-4Glc beta 1-1-Cer (IV4GalNAcGD1a). The monoclonal IgM appears to be reacting with the terminal [GalNAc beta 1-4Gal(3-2 alpha NeuAc)beta 1-] moiety shared by these three gangliosides and is a useful probe for detecting small amounts of GM2, IV4GalNAcGM1b, IV4GalNAcGD1a, and other gangliosides with the same terminal sugar configuration in tissues. Species distribution studies using the antibody revealed that GM2 is present in the brains and nerves of all species examined, while IV4GalNAcGM1b and IV4GalNAcGD1a exhibit some striking species specificity. GM2, but not IV4GalNAcGD1a, is enriched in purified myelin from human brain.

Topics: Animals; Antibodies, Monoclonal; beta-N-Acetylhexosaminidases; Brain Chemistry; Cats; Cattle; Chickens; Electrophoresis, Polyacrylamide Gel; Epitopes; G(M1) Ganglioside; G(M2) Ganglioside; Gangliosides; Guinea Pigs; Humans; Immunoglobulin M; Paraproteinemias; Peripheral Nervous System Diseases; Rabbits; Species Specificity; Subcellular Fractions