Monoclonal antibodies to myelin associated glycoprotein (MAG) in patients with sensory or mixed sensory-motor demyelinating polyneuropathies occurring in association with IgM gammopathy (paraproteinemia) are all directed toward carbohydrate epitopes in MAG and cross-react with other glycoproteins of PNS myelin including PO and PMP-22, as well as with the glycosphingolipid, sulfate-3-glucuronyl paragloboside (SGPG). We used enzyme-linked immunosorbent assays (ELISAs) and densitometry of immunostained Western blots or thin-layer chromatograms to compare the relative strengths of IgM binding from a series of 11 neuropathy patients of this type to the potential antigens in nerve. These patients previously had been part of a clinical trial of intravenous immunoglobulin (IVIg) in MNB. The IgM from all the patients reacted with SGPG, but the strengths of binding to SGPG did not correlate well with the strengths of binding to MAG or other glycoprotein antigens. There was a good correlation between the strengths of binding of the IgM antibodies to PO and PMP-22, but two of the patients exhibited exceptionally strong IgM reactivity to PO and PMP-2 relative to reactivity with MAG and SGPG. PO and PMP-22 are components of compact myelin, whereas MAG is restricted to the periaxonal Schwann cell membranes, incisures and lateral loops. SGPG has been reported to be in both myelin and axonal membranes. Therefore, these variations from patient to patient with regard to relative strengths of binding to potential target antigens may contribute to clinical variability, and the data are currently being analyzed for correlations with clinical and electrophysiological findings on the patients. Other patients with neuropathy frequently have monoclonal or polyclonal antibodies to ganglioside antigens in nerve. Clinical subsets of these patients include motor neuropathy in association with antibodies to GM1 ganglioside or sensory-ataxic neuropathy (SAN) in association with antibodies to gangliosides containing disialosyl moieties such as GD1b and GT1b. This year we have immunized Lewis rats with GM1 or GT1b as a step toward establishing animal models of these two forms of neuropathy in which to investigate pathogenic mechanisms. Chronic inflammatory demyelinating neuropathy (CIDP) sometimes occurs in association with malignant melanoma, and it has been suggested that it may be caused by induction of antibodies to glycolipid antigens shared between melanoma and neural antigens, both of which are of neuroectodermal origin. This hypothesis was supported by our finding of antibodies to SGPG and to GM2 ganglioside in a patient with melanoma and CIDP.
