Bartfeld D, Fuchs S
Proc Natl Acad Sci U S A. 1978 Aug;75(8):4006-10. doi: 10.1073/pnas.75.8.4006.
Specific immunosuppression of experimental autoimmune myasthenia gravis (EAMG) was achieved by the use of a denatured preparation of the acetylcholine receptor (AcChoR) that did not in itself induce the disease. Torpedo californica AcChoR was irreversibly denatured by complete reduction and carboxymethylation in 6 M guanidine hydrochloride. Rabbits immunized with reduced carboxymethylated receptor (RCM-AcChoR) produced antibodies that reacted with both RCM-AcChoR and intact AcChoR. The specificity of anti-RCM-AcChoR antibodies is different from that of anti-AcChoR antibodies because the former are directed to only part of the antigenic determinants present in the intact receptor. RCM-AcChoR, which by itself is completely nonmyasthenic, was shown to be capable of both preventing the onset of EAMG and of reversing the clinical symptoms in myasthenic rabbits. In all cases the therapeutic effect of RCM-AcChoR administration on EAMG was accompanied by a change in the immunological specificity of the antibodies. The crossreactivity between AcChoR and RCM-AcChoR and the nonpathogenicity of RCM-AcChoR appear to be crucial in governing the specific immunosuppressive effects of RCM-AcChoR on EAMG.
通过使用一种本身不会诱发疾病的变性乙酰胆碱受体（AcChoR）制剂，实现了对实验性自身免疫性重症肌无力（EAMG）的特异性免疫抑制。加州电鳐的AcChoR在6M盐酸胍中通过完全还原和羧甲基化而不可逆地变性。用还原羧甲基化受体（RCM-AcChoR）免疫的兔子产生的抗体与RCM-AcChoR和完整的AcChoR都发生反应。抗RCM-AcChoR抗体的特异性与抗AcChoR抗体不同，因为前者仅针对完整受体中存在的部分抗原决定簇。RCM-AcChoR本身完全无重症肌无力症状，已证明它既能预防EAMG的发作，又能逆转重症肌无力兔子的临床症状。在所有情况下，给予RCM-AcChoR对EAMG的治疗效果都伴随着抗体免疫特异性的改变。AcChoR与RCM-AcChoR之间的交叉反应性以及RCM-AcChoR的无致病性似乎在决定RCM-AcChoR对EAMG的特异性免疫抑制作用中起关键作用。
