Bain P G, Motomura M, Newsom-Davis J, Misbah S A, Chapel H M, Lee M L, Vincent A, Lang B
Department of Clinical Neurology, University of Oxford, UK.
Neurology. 1996 Sep;47(3):678-83. doi: 10.1212/wnl.47.3.678.
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.
静脉注射免疫球蛋白可改善多种抗体介导的自身免疫性疾病，但其作用机制尚不清楚。我们研究了其对肌肉力量以及对可能在兰伯特-伊顿肌无力综合征（LEMS）中致病的钙通道自身抗体血清滴度的影响。在一项随机、双盲、安慰剂对照的交叉试验中，采用曲线下面积法，在8周的时间内比较了9例患者的肢体、呼吸和延髓肌肉力量的系列指标以及钙通道抗体的血清滴度，连续两天每天按1 g/kg体重输注免疫球蛋白（总剂量2.0 g/kg体重）或安慰剂（等量体积的0.3%白蛋白）。使用125I-ω-芋螺毒素MVIIC通过放射免疫测定法测量钙通道抗体。在此测定中测试了免疫球蛋白的直接抗独特型作用。输注免疫球蛋白后，三项力量指标有显著改善（p = 0.017至0.038），同时血清钙通道抗体滴度显著下降（p = 0.028）。改善在2至4周达到峰值，到8周时下降。然而，平均血清滴度在1周时未改变，并且在体外未证实免疫球蛋白的直接抗独特型中和作用。我们得出结论，免疫球蛋白可使LEMS患者的肌肉力量短期内得到改善，这可能是由于诱导的钙通道自身抗体减少所致。这种减少不是由于免疫球蛋白的直接中和作用，但不能排除延迟的抗独特型作用。静脉注射免疫球蛋白后在其他自身抗体介导的疾病中的改善可能同样与致病性自身抗体水平的下降有关。
