asialo-gm1-ganglioside and Autoimmune-Diseases

A series of monoclonal IgM anti-GM1 ganglioside antibodies has been cloned from peripheral blood lymphocytes of patients with multifocal motor neuropathy and Guillain-Barré syndrome. In solid-phase immunoassay, the antibodies react with GMI, and also in differing degrees to the structurally related glycolipids asialo-GM1 (GA1) and GD1b. Here we describe the binding patterns of six human anti-GM I antibodies to epitopes within the human nervous system. Antibodies were observed to bind to motor neurons and spinal grey matter, dorsal and ventral spinal roots, dorsal root ganglion neurons, nodes of Ranvier, neuromuscular junctions and skeletal muscle. The distribution of immunoreactive epitopes, which included sensory structures, extended beyond those sites conventionally regarded as pathologically affected in anti-GM1 antibody-associated motor nerve syndromes. This undermines a model of disease pathogenesis based solely on antigen distribution. Factors other than the presence or absence of antigen, such as the local ganglioside topography, antibody penetration into, and pathophysiological vulnerability of a particular site may also influence the clinicopathological outcome of anti-GM1 antibody-mediated autoimmune attack.

Topics: Antibodies, Monoclonal; Autoimmune Diseases; Diaphragm; Epitopes; Femoral Nerve; G(M1) Ganglioside; Ganglia, Spinal; Gangliosides; Humans; Immunoglobulin M; Motor Neuron Disease; Nerve Tissue Proteins; Organ Specificity; Peripheral Nerves; Polyradiculoneuropathy; Spinal Cord; Spinal Nerve Roots

Although changes in surface carbohydrate expression of abnormally expanded MRL/Mp-lpr/lpr (MRL/lpr) lymph node (LN) cells have previously been described, the composition and function of glycolipids present on these cells as well as the spectrum of specificity of anti-carbohydrate antibodies reactive with these cells remains obscure. Analysis of antibodies to a panel of 22 carbohydrate structures using a liposome immune lysis assay (LILA) showed that, except for anti-asialo GM2 (GA2) antibodies, marked reduction of antiglycolipid antibody levels was observed in sera from 4-mo-old MRL/lpr mice compared with these from MRL/Mp(-)+/+ (MRL/+) mice. Absorption experiments revealed that both anti-asialo GM1 (GA1) and globoside antibodies had binding capacity to MRL/lpr LN cells. To elucidate the glycolipid profiles of MRL/lpr LN cells, glycolipids were extracted from LN cells of both MRL/lpr and MRL/+ mice and analysed. A 30-fold elevation of GM1 was found in MRL/lpr LN cells compared with MRL/+ LN cells. From the results of LILA using GA1/GM1 mixed liposomes, aberrantly expressed GM1 inhibited the classical complement pathway but did not interfere with the binding of anti-GA1 antibodies to liposomal GA1. These findings suggest that a drastic GM1 increase on MRL/lpr LN cells would inhibit the action of anti-GA1 antibodies and complement on the cell surface. This may explain the escape of these cells from an activated self directed immune response.

Topics: Animals; Antibody Specificity; Autoantibodies; Autoimmune Diseases; Carbohydrate Sequence; Complement System Proteins; G(M1) Ganglioside; Glycolipids; Liposomes; Lymph Nodes; Lymphoproliferative Disorders; Mice; Mice, Inbred Strains; Mice, Mutant Strains; Molecular Sequence Data

Serum IgG in a patient with chronic polyneuropathy after Mycoplasma pneumoniae infection reacted with ganglioside GM1, GD1b and asialo-GM1 on thin-layer chromatograms using an immunostaining technique as well as an enzyme-linked immunosorbent assay, suggesting that the galactosyl (beta 1-3)N-acetylgalactosaminyl moiety could be a target antigen in this patient. Serum IgG reacting with these glycolipids may be involved in the pathogenesis of both motor and sensory neuropathies in this patient.

Topics: Adolescent; Adult; Aged; Autoantibodies; Autoimmune Diseases; Child; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Gangliosides; Humans; Immunoglobulin G; Male; Middle Aged; Neurologic Examination; Pneumonia, Mycoplasma; Polyradiculoneuropathy

BB rats exhibit a syndrome of spontaneous diabetes that has clinical and pathological characteristics analogous to those found in human insulin-dependent diabetes mellitus (IDDM). Islet tissue transplanted into spontaneously diabetic BB rats is uniformly destroyed by a recurrence of the autoimmune response that destroyed the diabetic subject's native islets. To examine recurrent autoimmune destruction of transplanted islets, it is necessary to exclude islet damage that might result from allograft rejection. We utilized neonatal tolerance induction to prevent rejection of Wistar-Furth (WF) (RT1u) islet allografts by spontaneously diabetic BB recipients. We determined that islet-recipient treatment with anti-asialo-GM1 (anti-AGM1) antibody prevents recurrent autoimmune diabetes that would otherwise destroy transplanted WF islet grafts. Anti-AGM1 therapy significantly decreased peripheral blood natural killer (NK) cell activity. These data suggest a role for NK cells in the pathogenesis of recurrent diabetes in neonatally tolerant BB rats.

Topics: Animals; Autoimmune Diseases; Diabetes Mellitus, Experimental; G(M1) Ganglioside; Glycosphingolipids; Immune Sera; Immune Tolerance; Islets of Langerhans; Islets of Langerhans Transplantation; Killer Cells, Natural; Rats; Rats, Inbred BB; Rats, Inbred WF; Recurrence

Topics: Animals; Autoantibodies; Autoimmune Diseases; Brain Neoplasms; Cell Line; Cytotoxicity Tests, Immunologic; G(M1) Ganglioside; Glycosphingolipids; Guinea Pigs; Humans; Lupus Erythematosus, Systemic; Mice; Nervous System Diseases; Rabbits