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

GM2 ganglioside is a potential peripheral nerve antigen for neuropathy-associated autoantibodies. However little data are available on their pathogenic effects, if any. In this study we have screened both neuropathy-associated 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 population, as well as in patients with peripheral neuropathies and other neurological diseases. GM2 antibodies were either mono-reactive, cross-reactive with GM1a, or cross-reactive with GalNAc-GM1b and/or GalNAc-GD1a. All GM2 antisera from neuropathy subjects and normal controls bound to, and were capable of complement-mediated lysis of the NSC-34 cell line which expresses high levels of membrane-associated GM2. However, in immunohistological studies on human and rodent peripheral nervous system tissues, no specific binding was seen with GM2 antisera, either cross-reactive with GalNAc-GM1b and GalNAc-GDla, or with GM1a. These data indicate that although GM2 antisera can lyse neural membranes containing GM2, this antigen(s) is not detectable by standard immunohistological techniques in human or rodent peripheral nerve. This raises doubts about their pathophysiological significance in human autoimmune neuropathy

Antiglycolipid antibodies, immunoglobulins and paraproteins in motor neuron disease: a population based case-control study

The role of humoral autoimmune factors in the pathogenesis of motor neuron disease (MND) is currently under considerable scrutiny. In particular, there have been many reports of abnormal serum immunoglobulin patterns and elevated titres of anti-ganglioside antibodies in patients with MND. However, many of these studies may be biased by the selection criteria for patients and controls. In order to carefully address this issue we obtained 82 blood samples from consecutive MND patients identified through a national MND register in combination with 82 community controls matched for age, sex and geographical area. We used these samples to determine the frequency of monoclonal immunoglobulins (mIgs) and measure the levels of serum immunoglobulins and anti-GM1 ganglioside antibodies in sporadic cases of MND in comparison with normal controls. Serum mIgs detected using high resolution and immunofixation agarose electrophoresis were present in 1.2% of MND patients and 2.4% of controls. Using a highly sensitive isoelectric focusing and immunoblotting method, monoclonal or oligoclonal immunoglobulins were found in 28% of MND patients and 27% of controls. Anti-GM1 antibodies were present in 26% of MND patients and 18% of controls (odds ratio = 1.5, 95%, CI 0.7-3.6) with no significant differences in titres between the 2 groups. Mean immunoglobulin G, A and M levels were equal in 2 groups. Thus, although alterations in these parameters were identified, we were unable to demonstrate any significant difference between MND patients and controls. We conclude that the majority of sporadic cases of MND are unlikely to have an autoimmune basis as judged by the lack of abnormalities in these parameters