SPECIFICITIES OF ANTIBODIES TO ACETYLCHOLINE-RECEPTORS IN SERA FROM MYASTHENIA-GRAVIS PATIENTS MEASURED BY MONOCLONAL-ANTIBODIES
SPECIFICITIES OF ANTIBODIES TO ACETYLCHOLINE-RECEPTORS IN SERA FROM MYASTHENIA-GRAVIS PATIENTS MEASURED BY MONOCLONAL-ANTIBODIES
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DOI：
10.1073/pnas.79.1.188
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发表时间：
1982-01-01
期刊：
影响因子：
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通讯作者：
LINDSTROM, JM
中科院分区：
文献类型：
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作者：
TZARTOS, SJ;SEYBOLD, ME;LINDSTROM, JM
重症肌无力 (MG) 患者血清中抗体特异性的模式是通过针对乙酰胆碱受体分子上确定的决定簇的单克隆抗体抑制血清抗体与人类肌肉受体结合的能力来确定的。重症肌无力患者产生的特异性模式与用从鱼类电器官或哺乳动物肌肉纯化的受体免疫的动物产生的特异性模式基本相同。大多数抗体针对位于α细胞外表面的主要免疫原性区域。亚基并且不同于乙酰胆碱结合位点。 .beta 上的区域。和.gamma。主要免疫原性区域附近的亚基也具有显着的免疫原性。在一名患者中，尽管总抗体量和临床状态发生变化，但不同区域的抗体比例随时间保持恒定。患者之间的抗体特异性和临床状态之间没有明显的相关性。重症肌无力的自身免疫反应可能是由人类受体而不是交叉反应（例如病毒）抗原刺激的。在 MG 和实验性自身免疫性 MG 中，产生的特异性模式可能是由受体分子固有的免疫原性结构特征决定的。有时在具有相同抗受体抗体总浓度的患者之间观察到的临床状态的巨大差异可能主要是由于影响神经肌肉传递安全系数的内源性因素的差异，而不是由于存在特别致病性的抗受体特异性。
The pattern of antibody specificities in sera from patients with myasthenia gravis (MG) was determined by the ability of monoclonal antibodies against defined determinants on the acetylcholine receptor molecule to inhibit binding of the serum antibodies to receptor from human muscle. MG patients produce fundamentally the same pattern of specificities as that produced by animals immunized with receptor purified from fish electric organs or mammalian muscle. Most of the antibodies are directed at the main immunogenic region which is located on the extracellular surface of the .alpha. subunit and is distinct from the acetylcholine binding site. Regions on the .beta. and .gamma. subunits near the main immunogenic region are also significantly immunogenic. In 1 patient the proportions of antibodies to various regions are constant over time despite changes in total antibody amount and clinical state. Between patients there is no obvious correlation between antibody specificities and clinical state. The autoimmune response in MG is probably stimulated by human receptor rather than a crossreacting (e.g., viral) antigen. In both MG and experimental autoimmune MG the pattern of specificities produced is probably determined by the inherently immunogenic structural features of the receptor molecule. The wide differences in clinical state sometimes observed between patients with the same total concentration of antireceptor antibody may be due primarily to differences in endogenous factors which affect the safety factor for neuromuscular transmission rather than to the presence of especially pathogenic antireceptor specificities.