Sinmaz Nese, Nguyen Tina, Tea Fiona, Dale Russell C, Brilot Fabienne
Brain Autoimmunity Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children's Hospital at Westmead, University of Sydney, Locked Bag 4001, Westmead, NSW, 2145, Australia.
Discipline of Child and Adolescent Health, Sydney Medical School, University of Sydney, Sydney, Australia.
J Neuroinflammation. 2016 Aug 30;13(1):219. doi: 10.1186/s12974-016-0678-4.
Our knowledge of autoantibody-associated diseases of the central (CNS) and peripheral (PNS) nervous systems has expanded greatly over the recent years. A number of extracellular and intracellular autoantigens have been identified, and there is no doubt that this field will continue to expand as more autoantigens are discovered as a result of improved clinical awareness and methodological practice. In recent years, interest has shifted to uncover the target epitopes of these autoantibodies.
The purpose of this review is to discuss the mapping of the epitope targets of autoantibodies in CNS and PNS antibody-mediated disorders, such as N-methyl-D-aspartate receptor (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), leucine-rich glioma-inactivated protein 1 (Lgi1), contactin-associated protein-like 2 (Caspr2), myelin oligodendrocyte glycoprotein (MOG), aquaporin-4 (AQP4), 65 kDa glutamic acid decarboxylase (GAD65), acetylcholine receptor (AChR), muscle-specific kinase (MuSK), voltage-gated calcium channel (VGCC), neurofascin (NF), and contactin. We also address the methods used to analyze these epitopes, the relevance of their determination, and how this knowledge can inform studies on autoantibody pathogenicity. Furthermore, we discuss triggers of autoimmunity, such as molecular mimicry, ectopic antigen expression, epitope spreading, and potential mechanisms for the rising number of double autoantibody-positive patients.
Molecular insights into specificity and role of autoantibodies will likely improve diagnosis and treatment of CNS and PNS neuroimmune diseases.
近年来，我们对中枢神经系统（CNS）和周围神经系统（PNS）自身抗体相关疾病的认识有了极大扩展。已经鉴定出许多细胞外和细胞内自身抗原，并且毫无疑问，随着临床意识和方法实践的改进发现更多自身抗原，该领域将继续扩展。近年来，人们的兴趣已转向揭示这些自身抗体的靶表位。
本综述的目的是讨论在中枢神经系统和周围神经系统抗体介导的疾病中自身抗体表位靶标的定位，这些疾病包括N-甲基-D-天冬氨酸受体（NMDAR）、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）、富含亮氨酸的胶质瘤失活蛋白1（Lgi1）、接触蛋白相关蛋白样2（Caspr2）、髓鞘少突胶质细胞糖蛋白（MOG）、水通道蛋白4（AQP4）、65 kDa谷氨酸脱羧酶（GAD65）、乙酰胆碱受体（AChR）、肌肉特异性激酶（MuSK）、电压门控钙通道（VGCC）、神经束蛋白（NF）和接触蛋白。我们还讨论了用于分析这些表位的方法、其测定的相关性，以及这些知识如何为自身抗体致病性研究提供信息。此外，我们讨论了自身免疫的触发因素，如分子模拟、异位抗原表达、表位扩展，以及双自身抗体阳性患者数量增加的潜在机制。
对自身抗体特异性和作用的分子见解可能会改善中枢神经系统和周围神经系统神经免疫疾病的诊断和治疗。
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