Effects of intravenous immunoglobulin on muscle weakness and calcium-channel autoantibodies in the Lambert-Eaton myasthenic syndrome.
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 using 125I-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 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.
Bain
P G
PG
Department of Clinical Neurology, University of Oxford, UK.
Motomura
M
M
Newsom-Davis
J
J
Misbah
S A
SA
Chapel
H M
HM
Lee
M L
ML
Vincent
A
A
Lang
B
B
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D015220:Calcium Channels / Q000276:immunology*; D004311:Double-Blind Method; D004576:Electromyography; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D015624:Lambert-Eaton Myasthenic Syndrome / Q000503:physiopathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000503:physiopathology*; D013997:Time Factors
D001323:Autoantibodies; D015220:Calcium Channels; D016756:Immunoglobulins, Intravenous