Jacobs Bart C, Bullens Roland W M, O'Hanlon Graham M, Ang C Wim, Willison Hugh J, Plomp Jaap J
Departments of Neurology and Immunology, Erasmus Medical Center Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
Muscle Nerve. 2002 Apr;25(4):549-58. doi: 10.1002/mus.10060.
Anti-GQ1b antibodies are associated with the Miller Fisher syndrome (MFS), a variant of the Guillain-Barré syndrome (GBS). In the ex vivo mouse diaphragm, anti-GQ1b-positive MFS serum induces muscle fiber twitching, a temporary dramatic increase of spontaneous quantal acetylcholine release, and transmission blockade at neuromuscular junctions (NMJs). These effects resemble those of alpha-latrotoxin (alpha-LTx) and are induced by antibody-mediated activation of complement. We developed an assay for detection of the alpha-LTx-like effect, using muscle fiber twitching as indicator. We tested 89 serum samples from GBS, MFS, and control subjects, and studied correlations with clinical signs, anti-ganglioside antibodies, micro-electrode physiology, and complement deposition at NMJs. Twitching was observed with 76% of the MFS and 10% of the GBS samples. It was associated with ophthalmoplegia and anti-GQ1b antibodies in patients, and with increased spontaneous acetylcholine release and C3c-deposition at mouse NMJs. This study strongly suggests that antibodies to GQ1b (with cross-reactivity to related gangliosides) are responsible for the alpha-LTx-like activity. The twitching assay is an efficient test for detection of this effect, and allows for screening of large numbers of samples and modifying drugs.
抗GQ1b抗体与格林-巴利综合征（GBS）的一种变异型——米勒-费雪综合征（MFS）相关。在体外小鼠膈肌实验中，抗GQ1b阳性的MFS血清可诱导肌纤维抽搐、自发性量子化乙酰胆碱释放的暂时急剧增加以及神经肌肉接头（NMJ）处的传递阻滞。这些效应类似于α-银环蛇毒素（α-LTx）的效应，并且是由抗体介导的补体激活所诱导的。我们开发了一种检测α-LTx样效应的检测方法，以肌纤维抽搐作为指标。我们检测了89份来自GBS、MFS和对照受试者的血清样本，并研究了其与临床体征、抗神经节苷脂抗体、微电极生理学以及NMJ处补体沉积的相关性。在76%的MFS样本和10%的GBS样本中观察到了抽搐现象。它与患者的眼肌麻痹和抗GQ1b抗体相关，并且与小鼠NMJ处自发性乙酰胆碱释放增加和C3c沉积相关。这项研究强烈表明，针对GQ1b的抗体（与相关神经节苷脂存在交叉反应性）是造成α-LTx样活性的原因。抽搐检测是检测这种效应的一种有效方法，并且可以用于筛查大量样本以及测试药物。
