Scotton William J, Karim Abid, Jacob Saiju
Department of Neurology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Department of Neuroimmunology, University of Birmingham, Birmingham, UK.
Methods Mol Biol. 2019;1941:225-255. doi: 10.1007/978-1-4939-9077-1_15.
Immune-mediated inflammation of the brain has been recognized for more than 50 years, although the initial descriptions were mainly thought to be secondary to an underlying neoplasm. Some of these paraneoplastic encephalitides express serum antibodies, but these were not thought to be pathogenic but instead have a T-cell-mediated pathophysiology. Over the last two decades, several pathogenic antibodies against neuronal surface antigens have been described in autoimmune encephalitis, which are amenable to immunotherapy. Several of these antibodies are directed against glutamate receptors (GluRs). NMDAR encephalitis (NMDARE) is the most common of these antibodies, and patients often present with psychosis, hallucinations, and reduced consciousness. Patients often progress on to develop confusion, seizures, movement disorders, autonomic instability, and respiratory depression. Although initially described as exclusively occurring secondary to ovarian teratoma (and later other tumors), non-paraneoplastic forms are increasingly common, and other triggers like viral infections are now well recognized. AMPAR encephalitis is relatively less common than NMDARE but is more likely to paraneoplastic. AMPAR antibodies typically cause limbic encephalitis, with patients presenting with confusion, disorientation, memory loss, and often seizures. The syndromes associated with the metabotropic receptor antibodies are much rarer and often can be paraneoplastic-mGluR1 (cerebellar degeneration) and mGluR5 (Ophelia syndrome) being the ones described in literature.With the advance in molecular biology techniques, it is now possible to detect these antibodies using cell-based assays with high sensitivity and specificity, especially when coupled with brain tissue immunohistochemistry and binding to live cell-based neurons. The rapid and reliable identification of these antibodies aids in the timely treatment (either in the form of identifying/removing the underlying tumor or instituting immunomodulatory therapy) and has significantly improved clinical outcome in this otherwise devastating group of conditions.
脑的免疫介导性炎症已被认识超过50年，尽管最初的描述主要被认为是继发于潜在肿瘤。其中一些副肿瘤性脑炎可表达血清抗体，但这些抗体当时并不被认为具有致病性，而是具有T细胞介导的病理生理学机制。在过去二十年中，自身免疫性脑炎中已描述了几种针对神经元表面抗原的致病性抗体，这些抗体适用于免疫治疗。其中几种抗体针对谷氨酸受体（GluRs）。N-甲基-D-天冬氨酸受体脑炎（NMDARE）是这些抗体中最常见的，患者常表现为精神病、幻觉和意识减退。患者通常会进一步发展为意识模糊、癫痫发作、运动障碍、自主神经功能不稳定和呼吸抑制。尽管最初被描述为仅继发于卵巢畸胎瘤（以及后来的其他肿瘤），但非副肿瘤性形式越来越常见，现在病毒感染等其他触发因素也已得到充分认识。α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体脑炎（AMPAR）比NMDARE相对少见，但更可能是副肿瘤性的。AMPAR抗体通常引起边缘叶脑炎，患者表现为意识模糊、定向障碍、记忆丧失，且常伴有癫痫发作。与代谢型受体抗体相关的综合征更为罕见，且通常可能是副肿瘤性的——代谢型谷氨酸受体1（小脑变性）和代谢型谷氨酸受体5（奥菲莉亚综合征）是文献中描述的类型。随着分子生物学技术的进步，现在可以使用基于细胞的检测方法以高灵敏度和特异性检测这些抗体，特别是与脑组织免疫组织化学以及与基于活细胞的神经元结合时。这些抗体的快速可靠鉴定有助于及时治疗（以识别/切除潜在肿瘤或进行免疫调节治疗的形式）并显著改善了这类原本具有毁灭性疾病的临床结局。
