Neuropathy associated with dysglobulinemia and monoclonal gammopathy

Monoclonal gammopathy, especially monoclonal gammopathy of undetermined significance (MGUS) with IgM M-components, are associated with demyelinating neuropathy. In approximately 50% of these patients, the IgM M-component reacts with myelin associated glycoprotein (MAG) or other subcomponents of myelin such as glycolipids or gangliosides and a pathogenetic role of the M component has been proposed. Polyneuropathies associated with monoclonal gammopathies are of interest because of the potential relationship between the monoclonal protein and immune-mediated nerve damage. Many patients have been described in whom polyneuropathy is associated with IgM or IgG monoclonal gammopathy. While some such patients have MGUS, others have a variety of malignant plasma cell dyscrasia. The associated polyneuropathies clinically, electrodiagnostically, and histologically heterogeneous, but some exhibit primarily demyelination features, while others show axonal features. I have reviewed clinical, and immunological data in patients with MGUS and polyneuropathy in our clinic. The mechanism of neuropathy in patients with monoclonal gammopathy in the field of immunological studies is also reviewed. In summary, antibody activity in patients with monoclonal gammopathies associated with peripheral neuropathies almost exclusively found in monoclonal proteins of the IgM class. The most prevalent antibody is directed against MAG. IgG and IgA monoclonal proteins did not react components of peripheral nerve myelin. IgM-MGUS neuropathy should be separated conceptionally from monoclonal IgG neuropathies from my data.