Antibody testing in peripheral neuropathies: a critical approach

Abstract

A number of autoantibodies that induce inflammation on autoimmune peripheral neuropathies have been described. We review the techniques to measure autoantibodies and assess the usefulness of antibody assays in acquired acute demyelinating neuropathies such as Guillain-Barre syndrome (GBS) and chronic acquired demyelinating neuropathies including CIDP, multifocal motor neuropathy and MGUS neuropathy. In acute acquired demyelinating neuropathies associations of clinical characteristics and specific infections and the presence of anti-ganglioside antibodies have been found. Since diagnostic criteria have been available to subclassify Guillain-Barre syndrome in different clinical variants including clinical, electrophysiological, pathological and immunological findings, several varieties have been described: pure motor forms, sensory forms, primary axonal and primary demyelinating varieties. However, further studies are necessary to validate the usefulness of this subclassification with respect to treatment and prognosis. This is particularly important if subgrouping of GBS patients may lead to more individualised treatment. It has been suggested that for the IgG anti-GM1-positive subgroup of GBS patients, IVlg therapy may be the more efficacious treatment than plasmapheresis. The spectrum of chronic acquired demyelinating polyneuropathies cover different entities that have recently been categorised in three major groups: chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN) and MGUS neuropathy. Though the majority of CIDP patients respond well to immunotherapy, no constant autoantibody activity has been reported. In MMN serum antibodies, mostly IgM to the ganglioside GM1 or less frequently to asialo-GM1, GD1a or GM2 have been reported by ELISA in a variable proportion of MMN patients with a prevalence for anti-GM1 IgM in most large series, ranging from 30 to 60%. The reasons for these discrepant figures are still unclear but may be related to differences in the ELISA procedure or in the controls used to establish normal reference values. Antibodies to the myelin-associated glycoprotein (MAG) are detected in 50 to 60% of patients with neuropathy and immunoglobulin M (IgM) monoclonal gammopathy. Most patients have a slowly progressive, sensory or sensorimotor, demyelinating polyneuropathy. A causal relation between anti-MAG antibodies and neuropathy is supported because pathologic studies of sural nerve biopsies of patients with neuropathy and anti-MAG IgM monoclonal gammopathy show demyelination associated with IgM deposits on the affected myelin sheaths. We conclude that testing for serum autoantibodies should never be the first step in the work-up of peripheral neuropathy but an additional diagnostic measure after careful clinical and electrophysiological evaluation. High quality standards for a diagnostic antibody test should be applied. In our experience anti-MAG antibodies are a valuable marker that is relevant for diagnosis. Patients with chronic demyelinating polyneuropathies should be screened for anti-MAG antibodies. We test all our patients with lower motor neuron disease or motor neuropathies for anti-GM1 antibodies. We do not routinely test for anti-GM1 or related gangliosides in Guillain-Barre syndrome as the results have not yet a definite impact on the diagnosis or treatment regimen.