Autoantibodies associated with peripheral neuropathy

High titers of serum antibodies to neural antigens occur in several forms of neuropathy. These include neuropathies associated with monoclonal gammopathy, inflammatory polyneuropathies, and paraneoplastic neuropathies. The antibodies frequently react with glycosylated cell surface molecules, including glycolipids, glycoproteins, and glycosaminoglycans, but antibodies to intracellular proteins have also been described. There are several correlations between antibody specificity and clinical symptoms, such as anti-MAG antibodies with demyelinating sensory or sensorimotor neuropathy, anti-GM1 ganglioside antibodies with motor nerve disorders, antibodies to gangliosides containing disialosyl moieties with sensory ataxic neuropathy and Miller-Fisher syndrome, and antibodies to the neuronal nuclear Hu antigens with paraneoplastic sensory neuronopathy. These correlations suggest that the neuropathies may be caused by the antibodies, but evidence for a causal relationship is stronger in some examples than others. In this review, we discuss the origins of the antibodies, evidence for and against their involvement in pathogenic mechanisms, and the implications of these findings for therapy.