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From the Departments of Clinical Neurology and Institute of Molecular Medicine (Drs. Bain, Motomura, Newsom-Davis, Vincent, and Lang), and Clinical Immunology (Drs. Misbah and Chapel), University of Oxford, UK, and UCLA School of Public Health and Medicine (Dr. Lee), Los Angeles, CA.
Supported by the Myasthenia Gravis Association/Muscular Dystrophy Group (UK), the Medical Research Council, UK, and Baxter Healthcare Corporation (Hyland division). Dr. Motomura holds a Wellcome Travelling Research Fellowship.
Received September 14, 1995. Accepted in final form February 27, 1996.
Address correspondence and reprint requests to Professor J. Newsom-Davis, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Intravenous immunoglobulin improves many antibody-mediated autoimmune disorders, but its mode of action is unknown. We investigated its effects on muscle strength and on the serum titer of the calcium-channel autoantibodies that are likely to be pathogenic in the Lambert-Eaton myasthenic syndrome (LEMS). In a randomized, double-blind, placebo-controlled crossover trial, serial indices of limb, respiratory, and bulbar muscle strength and the serum titer of calcium-channel antibodies in nine patients were compared over an 8-week period, using the area-under-the-curve approach, following infusion on two consecutive days of immunoglobulin at 1 g/kg body weight/day (total dose 2.0 g/kg body weight) or placebo (equivalent volume of 0.3% albumin). Calcium-channel antibodies were measured by radioimmunoassay using125 I-omega-conotoxin MVIIC. Direct anti-idiotypic actions of immunoglobulin were tested in this assay. Immunoglobulin infusion was followed by significant improvements in the three strength measures (p = 0.017 to 0.038) associated with a significant decline in serum calcium-channel antibody titers (p = 0.028). Improvement peaked at 2 to 4 weeks and was declining by 8 weeks. Mean serum titers were unchanged at 1 week, however, and direct anti-idiotypic antibody neutralization by immunoglobulin was not demonstrable in vitro. We conclude that immunoglobulin causes a short-term improvement in muscle strength in LEMS that probably results from the induced reduction in calcium-channel autoantibodies. The reduction is not due to a direct neutralizing action of the immunoglobulin, but a delayed anti-idiotypic action cannot be excluded. Improvement following intravenous immunoglobulin in other autoantibody-mediated disorders may similarly be associated with decline in levels of pathogenic autoantibodies.
NEUROLOGY 1996;47: 678-683
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