Novel lacto-ganglio type gangliosides with G(M2)-epitope in bovine brain which react with IgM from a patient of the amyotrophic lateral sclerosis- like disorder

A motor neuron disorder resembling that of amyotrophic lateral sclerosis was found in a patient who had received the intramuscular administration of a mixture of bovine brain gangliosides (Yuki, N., Sato, S., Miyatake, T., Sugiyama, K., Katagiri, T., and Sasaki, H. (1991) Lancet 337, 1109-1110). A very high titer of anti-G(M2) IgM was detected in the patient's serum and the patient quickly recovered after plasmapheresis. The clinical course of the patient appeared to be different from amyotrophic lateral sclerosis and the anti-G(M2) IgM was thought to be the culprit. The IgM reacted with G(M2), G(M1b)-GalNAc, SPG(α2-3)-GalNAc, and G(D1a)-GalNAc, but not with G(A2) or G(D2), meaning that the epitope recognized by the IgM was the G(M2)-like terminal structure GalNAcβ1-4(NeuAcα2-3)Galβ1-. In this study, we found two novel G(M2)-epitope containing gangliosides, X1 and X2, in bovine brain gangliosides by TLC immunostaining using the patient's IgM. They were characterized as unique lacto-ganglio type gangliosides. Their unusual structures may be immunogenic to humans to induce anti-G(M2) antibody.