Factors defining target specificity in antibody-mediated neuropathy: density-dependent binding of anti-GD1a polyclonal IgG from a neurological patient.

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.

Characterization of anti-ganglioside antibodies present in normal human plasma.

Samples of plasma from normal human adults were screened for anti-ganglioside antibodies by HPTLC-immunostaining and enzyme-linked immunosorbent assay (ELISA). All the samples analyzed showed IgM-immunoreactivity to GM1 ganglioside and its related glycolipid GA1. Reactivity to GD1b, GM2 and LM1 was also detected in 85, 80 and 20% of the analyzed samples, respectively. The main immunoreactivity is related to the asialo-ganglioside GA1. Using inhibition by soluble antigen and affinity chromatography techniques it was possible to distinguish two populations of anti-GA1 antibodies. One with high affinity reacting only with GA1, and another with low affinity reacting also with GM1 and GD1b. The antibodies that recognize GM2 are of low affinity and appear to be different from those that react with GA1. We postulate that the anti-GM1/GD1b immunoreactivity present in normal human plasma could be a cross-reaction of antibodies originally directed to a GA1-like carbohydrate structure. Anti-GA1 and anti-GM1 titers were calculated as the reciprocal of the plasma dilution needed to obtain the half maximal antibody binding, a titer definition that we consider more suitable to compare data from different laboratories than those usually employed.