PT -期刊文章盟克里斯蒂娜帕特森AU -埃里克·兰开斯特TI -分子机制的自身抗体Contactin-associated蛋白质像2 (Caspr2) (P1.140) DP - 2017年4月18日TA -神经病学PG - P1.140 VI - 88 IP - 16补充4099 - //www.ez-admanager.com/content/88/16_Supple首页ment/P1.140.short 4100 - //www.ez-admanager.com/content/88/16_Supplement/P1.140.full所以Neurology2017 4月18日;88 AB -目的:确定自身抗体的致病机制Contactin-associated蛋白质像2 (Caspr2)。背景:细胞粘附分子(摄像头)扮演着重要的角色在Ranvier的形成的节点有髓鞘的轴突。自身抗体对轴突的摄像头,包括Caspr2,与神经系统疾病;然而,这些自身抗体的机械基础知之甚少。Caspr2与Contactin-2 juxtaparanode,这个协会是必要的电压门控钾通道的集群。自身抗体Caspr2联想到一种获得周围神经兴奋过度(Isaacs综合症),脑炎,Morvan综合症(获得neuromyotonia和脑炎)。有趣的是,自身抗体Caspr2主要是IgG4亚型。与其他免疫球蛋白类型,IgG4经历让每个抗体bi-specific hemi-antibody交换。这个属性使交联,内化目标抗原(在某种程度上类似于反NMDAR脑炎)的可能性,并有利于抑制与其他膜蛋白相互作用的机制。设计/方法:HEK细胞转染表达Caspr2和对待heat-inactivated Caspr2患者的血清抗体血清或控制。生物素酰化和免疫印迹被用来评估,内化和表面的Caspr2水平。 We have also replicated the interaction of Caspr2 with Contactin-2 in vitro using a solid phase binding assay, and are explored the ability of Caspr2 antisera to disrupt the interactions of Caspr2 with Contactin-2 as well as other CAMs.Results: Caspr2 autoantibodies had no effects on total levels, surface expression or internalization of Caspr2 in transfected HEK cells.Conclusions: Together this evidence supports our hypothesis that Caspr2 autoantibodies do not cause internalization of Caspr2 and that new paradigms are needed to understand the molecular mechanisms of IgG4 autoantibodies to CAMs. As a next step, we will test the specific hypothesis that autoantibodies to Caspr2 disrupt its interactions with other CAMs.Study Supported by: NINDS R25 NS065745 (KP) and K08 NS075142 (EL)Disclosure: Dr. Patterson has nothing to disclose. Dr. Lancaster has received personal compensation from Jansen for activities as a consultant.