asialo-gm1-ganglioside and Paraproteinemias

IgM, IgG, IgA, and IgG subclass anti-GM1, anti-GQ1b, and anti-asialo-GM1 (anti-GA1) antibodies, respectively, were investigated by ELISA in serum from neurological and other patients. Increased anti-GM1 occurred mostly in approximately 15-35% of the cases without statistical differences; high percentages were found in Guillain-Barré syndrome (GBS) preceded by gastrointestinal infection and multifocal motor neuropathy. Roughly, IgM anti-GM1 was most frequent; however, distinct IgG and IgA reactions were found i.a. in GBS. A particular IgM anti-mono- and disialoganglioside pattern occurred in a patient with sensorimotor neuropathy and paraproteinemia. Anti-GQ1b was elevated in all Miller-Fisher patients, with some prevalence of IgG2 among IgG subclasses. Cross-reactivity of anti-GQ1b was demonstrated with Campylobacter jejuni lipopolysaccharides. Increased anti-GM1 and/or anti-GA1 was more frequent in systemic lupus erythematosus with central nervous system involvement than without. Incidence of anti-GM1 and anti-GA1 in X-adrenoleukodystrophy was relatively high. Although anti-GSL antibodies seem to have limited diagnostic value, studies of isotypes, subclass patterns, and cross-reactivities may lead to further insight into the origin of (auto) immune responses and their immunepathogenetic role in disease.

Topics: Autoantibodies; Campylobacter Infections; Campylobacter jejuni; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Gangliosides; Gastrointestinal Diseases; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin Isotypes; Immunoglobulin M; Lipopolysaccharides; Nervous System Diseases; Paraproteinemias; Polyradiculoneuropathy

We tested monoclonal IgM anti-GM1 and asialo-GM1 antibodies from 6 patients with chronic motor neuropathies for binding to lipopolysaccharides (LPS) from three stains of Campylobacter jejuni. Four of the 6 patients showed strong reactivity with LPS from at least one of the three C. jejuni strains tested as shown by enzyme-linked immunosorbent assay or western blot. Preabsorption with GM1 or asialo-GM1, or blocking with cholera toxin, prevented antibody binding to LPS. These studies indicate that human anti-GM1 or anti-asialo-GM1 antibodies cross-react with LPS from certain strains of C. jejuni, and that bacterial LPS might provide antigenic stimuli for the activation of B cells expressing anti-GM1 antibodies.

Topics: Antibodies, Monoclonal; Arachis; Campylobacter jejuni; Cholera Toxin; Cross Reactions; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Glycolipids; Humans; Immunoglobulin M; Lectins; Lipopolysaccharides; Motor Neuron Disease; Paraproteinemias; Peanut Agglutinin; Plant Lectins; Species Specificity

Analysis of monoclonal human Ig that occur in association with lymphoproliferative diseases has provided valuable information about antibody structure and idiotypes. We analyzed 940 human sera that contained monoclonal IgM proteins for their ability to bind to four carbohydrate epitopes. Ten sera bound asialo-GM1, five of these sera also bound GM1, 10 bound to 3-fucosyllactosamine (3-FL), and one each bound to levan and galactan. Although the antibody activity in each serum was associated with a single L chain isotype, both kappa and lambda isotypes were represented among the proteins that bound to asialo-GM1 and to 3-FL. Some antibodies against asialo-GM1 were highly specific for this compound, whereas others cross-reacted with the structurally related gangliosides GM1 and GD1b. The antibodies to asialo-GM1 also varied considerably in their ability to lyse liposomes that contain asialo GM1. An association of IgM mAb against gangliosides with peripheral neuropathies has been reported recently, but only one of five patients whose antibodies reacted with GM1 ganglioside had a neuropathy. The antibodies that bound 3-FL exhibited narrower specificity, and less than 10% cross reactivity was noted with structurally related carbohydrates. The frequency of monoclonal proteins that bound 3-FL and asialo-GM1, approximately 1:100 sera for each specificity, was surprisingly high in view of the fact that both of these epitopes are expressed in human tissues. We suggest that these antibodies may be poly-specific and/or that the subset of B lymphocytes that synthesizes these anti-carbohydrate antibodies undergoes malignant transformation more frequently than other B lymphocytes.

Topics: Antibodies, Monoclonal; Antibody Specificity; G(M1) Ganglioside; Glycolipids; Glycosphingolipids; Immunoglobulin M; Lewis X Antigen; Lymphoproliferative Disorders; Oligosaccharides; Paraproteinemias