Peripheral neuropathy associated with anti-GM2 ganglioside antibodies: Clinical and immunopathological studies

GM2 ganglioside is a potential peripheral nerve antigen for neuropathy-asso ciated autoantibodies. However little data are available on their pathogeni c effects, if any. In this study we have screened both neuropathy-associate d and control sera for anti-GM2 antibodies and subsequently used high titre sera for immunohistological and complement mediated cytotoxicity studies. We identified abnormally elevated anti-GM2 antisera in the normal populatio n, as well as in patients with peripheral neuropathies and other neurologic al diseases. GM2 antibodies were either mono-reactive, cross-reactive with GM1a, or cross-reactive with GalNAc-GM1b and/or GalNAc-GD1a. All GM2 antise ra from neuropathy subjects and normal controls bound to, and were capable of complement-mediated lysis of the NSC-34 cell line which expresses high l evels of membrane-associated GM2. However, in immunohistological studies on human and rodent peripheral nervous system tissues, no specific binding wa s seen with GM2 antisera, either cross-reactive with GalNAc-GM1b and GalNAc -GD1a, or with GM1a. These data indicate that although GM2 antisera can lys e neural membranes containing GM2, this antigen(s) is not detectable by sta ndard immunohistological techniques in human or rodent peripheral nerve. Th is raises doubts about their pathophysiological significance in human autoi mmune neuropathy.