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

Densitometry of immunostained Western blots or thin layer chromatograms and enzyme-linked immunosorbent assays (ELISAs) were used to compare the relat ive strengths of IgM binding to myelin-associated glycoprotein (MAG). PO gl ycoprotein, peripheral myelin protein-22 (PMP-22), sulfate-3-glucuronyl par agloboside (SGPG)I and other potential target antigens in a series of eleve n patients with sensory or sensorimotor demyelinating neuropathy and IgM pa raproteinemia. The IgM from all patients exhibited reactivity with both MAG and SGPG, and then 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 strengt hs with which the antibodies bound to the potential target antigens and het erogeneity in their fine specificities. First, there was a poor correlation between the strength of binding to,MAG and to SGPG, respectively Second, r eactivity with MAG or SGPG in a few of the patients was only detected by on e of the two assay systems. Third, about one-third of the patients' IgM abs olutely required the sulfate on SGPG for reactivity,whereas the others reta ined some reactivity after removal of the sulfate. Fourth, IgM from two of the patients exhibited unusually strong reactivity with the proteins of com pact myelin, PO and PMP22, These relative differences in strengths of antib ody binding to the potential antigens were compared with the patients' clin ical 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 res ponse to IVIg. Two of the patients who responded had only mild elevations o f IgM antibodies to nerve glycoconjugates and exhibited some unusual immuno chemical and clinical characteristics in comparison to the other patients, The results demonstrate differences in the relative strengths with which an ti-MAG and anti-SGPG IgM antibodies from different patients bind to potenti al neural target antigens which may affect pathogenic mechanisms and respon se to therapy. Published by Elsevier Science B.V.