Clinical Information

Autoantibodies directed against myelin-associated glycoprotein (MAG) are associated with sensory motor demyelinating peripheral neuropathy. A distal acquired demyelinating symmetric (DADS) neuropathy phenotype is the most commonly associated presentation. Patients typically have a slowly progressive symmetric sensory ataxia with/without distal weakness and an IgM monoclonal gammopathy of undetermined significance. Nerve conductions studies typically demonstrate a characteristic progressive sensory predominant mixed axonal and demyelinating neuropathy with reduced distal conduction velocities that are greater distally. In general, patients with a DADS neuropathy show limited treatment responses to intravenous immunoglobulin and more aggressive immunotherapy may be needed. MAG antibody titers do not correlate with disease severity nor treatment responses. The presence of MAG antibodies is not exclusively diagnostic of an acquired neuropathy and results must be interpreted in the correct clinical and electrophysiological context. MAG antibodies are present in approximately 50% to 70% of those with an IgM M-protein and a DADS neuropathy phenotype. However, MAG antibodies may also be identified in those with an IgM M-protein and a chronic inflammatory demyelinating polyneuropathy (CIDP) presentation as well as in other IgM paraproteinemic disorders that present with neuropathy including in myeloma, lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia) and amyloid light chain (AL)-IgM primary amyloidosis. Higher MAG antibody titers (>10,000 Buhlmann titer unit) are better predictors of an electrophysiological DADS phenotype whereas low titer MAG antibodies may be associated with a more diverse group of neuropathies. Detection of MAG IgM antibody by enzyme-linked immunosorbent assay based on human MAG (100 kDa) antigen is significantly more sensitive and specific than MAG western blot and immunofluorescence assays using primate antigen.