ABSTRACT
Low affinity anti-GM1 IgM-antibodies are part of the normal repertoire of human plasma antibodies (Mizutamari et al.: J Neuroimmunol 50:215-220, 1994), a fact that is against the pathological role proposed for them in autoimmune diseases. Here we present evidence that these low affinity IgM-antibodies are devoid of complement-mediated lytic activity to GM1-liposomes, suggesting that they should not be considered harmful. In contrast to the absence in normal individuals, in the plasma of a patient with sensory polyneuropathy we detected high affinity anti-GM1 IgM-antibodies. Concomitant with the presence of these high affinity anti-GM1 IgM-antibodies, the patient plasma is capable of producing complement-mediated lysis of GM1-liposomes. These results suggest that an increase in the affinity of the naturally existing anti-GM1 antibodies could be the trigger that switches them from non-harmful to pathological.
Subject(s)
G(M1) Ganglioside/immunology , Immunoglobulin M/blood , Peripheral Nervous System Diseases/immunology , Adult , Chromatography, Affinity , Chromatography, Thin Layer , Complement System Proteins/immunology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin M/immunology , Liposomes , Peripheral Nervous System Diseases/bloodABSTRACT
IgM and IgG antibodies reacting with components of human brain gangliosides were detected in a patient bearing severe sensory ataxy. Using different chemical and immunological methods, the antigen was identified as the GD1a ganglioside. The antibodies showed antigen "density-dependent" binding, a property only observed in tumor-specific monoclonal antibodies. The relevance of this result in regard with target specificity of neuropathy-associated antibodies directed to ubiquitous glycolipids is discussed.