Gangliosides G(M2), IV⁴GalNAcG(M1b), and IV⁴GalNAcG(D1a) as antigens for monoclonal immunoglobulin M in neuropathy associated with gammopathy

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 GalNAcβ1-4Gal(3-2αNeuAc)β1-4Glcβ1-1Cer(G(M2)), GalNAcβ1-4Gal(3-2αNeuAc)β1-3GalNAcβ1-4Galβ1-4Glcβ1-1Cer(IV⁴Gal AcG(M1b), and GalNAcβ1-4Gal(3-2αNeu-Ac)β1-3GalNAcβ1-4βGal(3-2αNeuAc)β1-4Glcβ- 1-1-Cer(IV⁴GalNAcG(D1a). The monoclonal IgM appears to be reacting with the terminal [GalNAcβ1-4Gal(3-2αNeuAc)β1-] moiety shared by these three gangliosides and is a useful probe for detecting small amounts of G(M2), IV⁴GalNAcG(M1b), IV⁴GalNAcG(D1a), and other gangliosides with the same terminal sugar configuration in tissues. Species distribution studies using the antibody revealed that G(M2) is present in the brains and nerves of all species examined, while IV⁴GalNAcG(M1b) and IV⁴GalNAcG(D1a) exhibit some striking species specificity. G(M2), but not IV⁴GalNAcG(D1a), is enriched in purified myelin from human brain.