抗人乙酰胆碱受体单抗的致病性和可变区序列分析

Pathogenicityandsequenceanalysisofamousemonoclonalantibodyagainsthumanacetylcholinere┐ceptor

为探讨重症肌无力（ＭＧ）和实验性自身免疫性重症肌无力（ＥＡＭＧ）的发病机制，测定了小鼠抗人肌肉乙酰胆碱受体（ＡＣｈＲ）单抗Ｇ１０对健康大鼠的致病性以及Ｇ１０可变区核苷酸序列。Ｇ１０可使健康大鼠诱导出ＥＡＭＧ，其全身肌肉ＡＣｈＲ损失率达２８．８％±１４．０％。Ｇ１０的重链可变区（ＶＨ）基因由小鼠ＰＣ７１８３种系基因编码，与ＭＯＰＣ２１ＶＨ种系基因的同源性为９７．０％。Ｇ１０的轻链可变区（ＶＬ）基因与抗ＤＮＡ抗体的ＶＬ基因同源性为９６．２％。从此结果可以看出，Ｇ１０的重链（尤其是互补决定区３）在介导ＭＧ和ＥＡＭＧ中起更重要的作用。

Weinvestigatedthepathogenesisofmyastheniagravis(MG)ontheanimalmodelsofexperimentalautoimmunemyastheniagravis(EAMG).Thepathogenicityofamousemonoclonalan-tibody(G10)againsthumanmuscleacetylcholinereceptor(AChR)wasdeterminedontheratsandthenucleotideandaminoacidsequencesofvariableregionsofG10analyzed.G10passivelytrans-ferredintotheratswasabletoinduceEAMG,andAChRlossby28.8±14%.Theheavychainge-neticelementofG10,whichshoweda97.0%homologywithmostcloselyrelatedMOPC21germlineVH,wasderivedfromthemousePC7183germlinefamily.ThehomologyofvariableregionoflightchainbetweenG10andanti-DNAantibodywas96.2%.WewereoftheopinionthattheheavychainofmonoclonalantibodyagainstAChRplayedanimportantroleinmediatingMGandEAMG.