g(m2)-ganglioside and Amyotrophic-Lateral-Sclerosis

Topics: Amyotrophic Lateral Sclerosis; Antibodies; G(M2) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Nervous System Diseases

We report a case of amyotrophic lateral sclerosis (ALS) with IgM antibody against gangliosides GM2 and GD2. A 57-year-old woman presented with slowly progressive muscular weakness of the upper extremities and dysarthria. She fulfilled the clinical and electrophysiological criteria of ALS, and died from sudden suffocation about 3 years after the onset of illness. The patient's serum IgM antibody was shown to recognize the structure shared by GM2 and GD2. Since anti-GM2 antibodies have been implicated in motor neuropathy or motor neuron syndrome, this rare case might contribute to the understanding of the immunological aspects of ALS.

Topics: Amyotrophic Lateral Sclerosis; Antibodies; Fatal Outcome; Female; G(M2) Ganglioside; Gangliosides; Humans; Immunoglobulin M; Middle Aged

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.

Topics: Adolescent; Adult; Amyotrophic Lateral Sclerosis; Autoantibodies; Case-Control Studies; Cell Line; Cross Reactions; Cytotoxicity, Immunologic; G(M2) Ganglioside; Guillain-Barre Syndrome; Humans; Immunohistochemistry; Middle Aged; Motor Neuron Disease; Peripheral Nervous System Diseases

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-GM2 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-GM2 IgM was thought to be the culprit. The IgM reacted with GM2, GM1b-GalNAc, SPG(alpha 2-3)-GalNAc, and GD1a-GalNAc, but not with GA2 or GD2, meaning that the epitope recognized by the IgM was the GM2-like terminal structure, GalNAc beta 1-4(Neu-Ac alpha 2-3)Gal beta 1-. In this study, we found two novel GM2-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 containing the following branching structures. [formula: see text] Their unusual structures may be immunogenic to humans to induce anti-GM2 antibody.

Topics: Aged; Amyotrophic Lateral Sclerosis; Animals; Brain; Carbohydrate Sequence; Cattle; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Epitopes; G(M2) Ganglioside; Gangliosides; Humans; Immunoglobulin M; Magnetic Resonance Spectroscopy; Male; Molecular Sequence Data; Spectrometry, Mass, Fast Atom Bombardment; Tumor Cells, Cultured

Topics: Amyotrophic Lateral Sclerosis; Chromosome Mapping; Diagnosis, Differential; G(M2) Ganglioside; Gangliosidoses; Genes, Dominant; Genes, Recessive; Genotype; Hexosaminidases; Humans; Motor Neurons; Neuromuscular Diseases; Phenotype