Johns Hopkins Encephalitis Center, Division of Neuroimmunology and Neuroinfectious Diseases, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore 21287, MD, United States.
Johns Hopkins Encephalitis Center, Division of Neuroimmunology and Neuroinfectious Diseases, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore 21287, MD, United States.
J Neuroimmunol. 2022 Jul 15;368:577867. doi: 10.1016/j.jneuroim.2022.577867. Epub 2022 May 2.
In recent years, autoimmune encephalitis associated with antibodies against neuronal cell surface proteins has become a well-recognized phenomenon. Here, we describe clinical features and diagnosis of these conditions before turning to the mechanisms by which autoantibodies are generated and cause disease. The clinical syndrome typically evolves in a subacute fashion and is quite variable, although short-term memory loss, behavioral changes, and seizures are common. Laboratory and imaging parameters of inflammation are typically less overtly deranged than in infectious encephalitis. While the most common antibodies found are to the NMDA receptor or LGI1 protein, a growing number of autoantibodies have been described. Established triggers include tumors and infections, although in many cases neither is identified. It is becoming increasingly clear that host immunogenetics can play a part in disease susceptibility, with a prominent role of HLA haplotype in certain syndromes. Antibodies cause disease by several mechanisms, including direct blocking of ligand binding sites, receptor internalization, and activation of complement, governed in part by the subtype of IgG antibody present. Although in vitro and in vivo models have contributed to our understanding of the mechanisms of disease, numerous gaps in our knowledge of the immunopathogenesis remain, and newer disease models are needed. Insights gained from such approaches will inform our basic understanding of disease and will likely also translate into diagnostic and therapeutic advances.
近年来，与神经元细胞表面蛋白抗体相关的自身免疫性脑炎已成为一种公认的现象。在这里，我们描述了这些疾病的临床特征和诊断，然后再探讨自身抗体产生和导致疾病的机制。临床综合征通常以亚急性方式演变，且变化多样，尽管短期记忆丧失、行为改变和癫痫发作较为常见。炎症的实验室和影像学参数通常不如感染性脑炎明显异常。虽然最常见的抗体是针对 NMDA 受体或 LGI1 蛋白的，但越来越多的自身抗体已被描述。已确定的触发因素包括肿瘤和感染，尽管在许多情况下都无法确定。越来越明显的是，宿主免疫遗传学可能在疾病易感性中发挥作用，某些综合征中 HLA 单倍型起着重要作用。抗体通过多种机制引起疾病，包括直接阻断配体结合位点、受体内化和补体激活，这部分受存在的 IgG 抗体亚型的控制。尽管体外和体内模型有助于我们理解疾病的机制，但我们对免疫发病机制的认识仍存在许多空白，需要新的疾病模型。从这些方法中获得的见解将丰富我们对疾病的基本认识，并可能转化为诊断和治疗方面的进展。
