Verschuuren J J, Dalmau J, Tunkel R, Lang B, Graus F, Schramm L, Posner J B, Newsom-Davis J, Rosenfeld M R
Department of Neurology, Leiden University Hospital, The Netherlands.
Neurology. 1998 Feb;50(2):475-9. doi: 10.1212/wnl.50.2.475.
The sera of patients with Lambert-Eaton myasthenic syndrome (LEMS) contain autoantibodies against several extracellular and intracellular components of the voltage-gated calcium channel (VGCC)/synaptic vesicle release complex. An example of the latter are anti-beta-subunit antibodies (anti-MysB antibodies). We constructed a full-length cDNA clone of a human VGCC beta-subunit to produce purified beta-subunit fusion protein (MysB protein). Using this protein, we demonstrated that anti-beta-subunit antibodies are present in the sera of 23% of LEMS patients and only, in low titer, in 2% of small cell lung cancer patients without LEMS. The presence of anti-beta-subunit antibodies was closely associated with high titers of P/Q- and N-type VGCC antibodies. Immunization of rats with the purified MysB protein induced high antibody titers, but no signs of neurologic dysfunction were found. We conclude that anti-beta-subunit antibodies are not likely to interfere with ion channel function, but their presence could explain the cross-reactivity of LEMS sera with several subtypes of VGCCs and the lack of correlation between anti-VGCC antibody titer and clinical severity of disease.
兰伯特-伊顿肌无力综合征（LEMS）患者的血清中含有针对电压门控钙通道（VGCC）/突触小泡释放复合体的几种细胞外和细胞内成分的自身抗体。后者的一个例子是抗β亚基抗体（抗MysB抗体）。我们构建了人VGCCβ亚基的全长cDNA克隆，以产生纯化的β亚基融合蛋白（MysB蛋白）。利用这种蛋白，我们证明23%的LEMS患者血清中存在抗β亚基抗体，而在无LEMS的小细胞肺癌患者中只有2%存在低滴度的抗β亚基抗体。抗β亚基抗体的存在与高滴度的P/Q型和N型VGCC抗体密切相关。用纯化的MysB蛋白免疫大鼠可诱导产生高抗体滴度，但未发现神经功能障碍的迹象。我们得出结论，抗β亚基抗体不太可能干扰离子通道功能，但其存在可以解释LEMS血清与几种VGCC亚型的交叉反应性，以及抗VGCC抗体滴度与疾病临床严重程度之间缺乏相关性。
