Paraproteinemia-associated neuropathy with or without anti-myelin-associated glycoprotein antibody

Paraproteinemia-associated neuropathy (PAN) develops with paraproteinemia and is mainly caused by the monoclonal proliferation of mature B cells, especially monoclonal gammopathy of undetermined significance (MGUS). PAN tends to increase with age, and in a super-aging society, its frequency is expected to increase. Among paraproteinemias, the immunoglobulin (Ig)G type is most common, but the frequency of PAN is reported to be higher for the IgM type. IgG/IgA-type PAN includes MGUS, plasma cell myeloma, and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes syndrome. IgM-type PAN includes anti-myelin-associated glycoprotein antibody-associated neuropathy, chronic ataxic neuropathy with IgM antibody that recognizes disialosyl ganglioside and IgM-type PAN without anti-nerve antibodies. Light chain-type PAN includes immunoglobulin-related amyloidosis. PAN has the characteristics of a blood disease, as well as an immune-mediated disease, and is treated by immunotherapy. As an example, anti-myelin-associated glycoprotein antibody-associated neuropathy is treated with rituximab, plasmapheresis and intravenous immunoglobulin therapy, but their effectiveness has not been established. As novel treatments, lenalidomide, Bruton tyrosine kinase inhibitors, B-cell lymphoma 2 inhibitors and mimetic human natural killer-1 epitope polymers have been investigated. By analyzing the human natural killer-1-related sugar chain structure as an antigen, the selective removal of pathological antibodies might be a new therapeutic target.