Variability in the binding of anti-MAG and anti-SGPG antibodies to target antigens in demyelinating neuropathy and IgM paraproteinemia

Abstract

Densitometry of immunostained Western blots or thin layer chromatograms and enzyme-linked immunosorbent assays (ELISAs) were used to compare the relative strengths of IgM binding to myelin-associated glycoprotein (MAG), P0 glycoprotein, peripheral myelin protein-22 (PMP-22), sulfate-3-glucuronyl paragloboside (SGPG), and other potential target antigens in a series of eleven patients with sensory or sensorimotor demyelinating neuropathy and IgM paraproteinemia. The IgM from all patients exhibited reactivity with both MAG and SGPG, and there was a statistically significant correlation between the overlay assays and ELISAs for measuring the strength of IgM binding to MAG and to SGPG. However, the data revealed variations in the relative strengths with which the antibodies bound to the potential target antigens and heterogeneity in their fine specificities. First, there was a poor correlation between the strength of binding to MAG and to SGPG, respectively. Second, reactivity with MAG or SGPG in a few of the patients was only detected by one of the two assay systems. Third, about one-third of the patients' IgM absolutely required the sulfate on SGPG for reactivity, whereas the others retained some reactivity after removal of the sulfate. Fourth, IgM from two of the patients exhibited unusually strong reactivity with the proteins of compact myelin, P0 and PMP22. These relative differences in strengths of antibody binding to the potential antigens were compared with the patients' clinical presentations and with their responses to intravenous immunoglobulin (IVIg) therapy in a clinical trial in which they participated. For the most part, these variations did not correlate with clinical presentation, which was relatively homogeneous in this series of patients. However, an inverse relationship was noted between degree of reactivity to MAG by ELISA and response to IVIg. Two of the patients who responded had only mild elevations of IgM antibodies to nerve glycoconjugates and exhibited some unusual immunochemical and clinical characteristics in comparison to the other patients. The results demonstrate differences in the relative strengths with which anti-MAG and anti-SGPG IgM antibodies from different patients bind to potential neural target antigens which may affect pathogenic mechanisms and response to therapy.