Hello from the Other Side: How Autoantibodies Circumvent the Blood-Brain Barrier in Autoimmune Encephalitis.
Hello from the Other Side: How Autoantibodies Circumvent the Blood-Brain Barrier in Autoimmune Encephalitis.
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DOI：
10.3389/fimmu.2017.00442
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发表时间：
2017
影响因子：
7.3
通讯作者：
Cutforth T
中科院分区：
文献类型：
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作者：
Platt MP;Agalliu D;Cutforth T
针对神经元受体和突触蛋白的抗体与产生运动和精神障碍的自身免疫性脑炎(AE)有关。为了对神经回路发挥病理作用，针对中枢神经系统(CNS)靶标的自身抗体必须通过穿越血脑屏障(BBB)进入大脑和脊髓，血脑屏障是由排列在CNS血管内的内皮细胞形成的严密调控的通道。到目前为止，自身抗体引发的脑炎综合征的发病机制尚不清楚，几乎所有的脑炎综合征中，自身抗体是如何突破屏障的仍不清楚。细胞免疫机制和体液免疫机制在疾病发病机制中的相对重要性也在很大程度上仍未被探索。在这里，我们回顾了各种自身免疫性脑病的触发因素及其动物模型，以及血脑屏障的基本结构特征以及它们在不同中枢神经系统区域之间的差异，这一特征可能是自身免疫性脑炎发病机制的一些区域性方面的基础。然后我们讨论抗体和免疫细胞进入中枢神经系统的途径以及它们对AE的影响。最后，我们探索未来的治疗策略，可以保留或恢复屏障功能，从而限制免疫细胞和自身抗体向中枢神经系统的渗透。最近对中枢神经系统自身抗体进入的机械性洞察力表明，在目前消除循环自身抗体的短期治疗之外，未来的治疗干预方向很有希望。
Antibodies against neuronal receptors and synaptic proteins are associated with autoimmune encephalitides (AE) that produce movement and psychiatric disorders. In order to exert their pathological effects on neural circuits, autoantibodies against central nervous system (CNS) targets must gain access to the brain and spinal cord by crossing the blood–brain barrier (BBB), a tightly regulated gateway formed by endothelial cells lining CNS blood vessels. To date, the pathogenic mechanisms that underlie autoantibody-triggered encephalitic syndromes are poorly understood, and how autoantibodies breach the barrier remains obscure for almost all AE syndromes. The relative importance of cellular versus humoral immune mechanisms for disease pathogenesis also remains largely unexplored. Here, we review the proposed triggers for various autoimmune encephalopathies and their animal models, as well as basic structural features of the BBB and how they differ among various CNS regions, a feature that likely underlies some regional aspects of autoimmune encephalitis pathogenesis. We then discuss the routes that antibodies and immune cells employ to enter the CNS and their implications for AE. Finally, we explore future therapeutic strategies that may either preserve or restore barrier function and thereby limit immune cell and autoantibody infiltration into the CNS. Recent mechanistic insights into CNS autoantibody entry indicate promising future directions for therapeutic intervention beyond current, short-lived therapies that eliminate circulating autoantibodies.