Section Translational Neuroimmunology, Department of Neurology, Jena University Hospital , Jena, Germany.
Carl-Ludwig-Institute for Physiology, Medical Faculty, Leipzig University , Leipzig, Germany.
Expert Opin Ther Targets. 2021 Jan;25(1):37-47. doi: 10.1080/14728222.2021.1856370. Epub 2020 Dec 31.
Antibody-mediated encephalitides (AE) with pathogenic autoantibodies (aAB) against neuronal surface antigens are a growing group of diseases characterized by antineuronal autoimmunity in the brain. AE patients typically present with rapidly progressive encephalitis and characteristic disease symptoms dependent on the target antigen. Current treatment consists of an escalating immunotherapy strategy including plasma exchange, steroid application, and B cell depletion.
For this review, we searched Medline database and google scholar with inclusive dates from 2000. We summarize current treatment strategies and present novel therapeutic approaches of target-specific interventions at the pre-clinical level as well as immunotherapy directed at antibody-induced pathology. Treatment options include modulation of target proteins, intervention with downstream pathways, antibody modification, and depletion of antibody-secreting cells.
Although current therapies in AE are effective in many patients, recovery is often prolonged and relapses as well as persistent deficits can occur. Specific immunotherapy together with supportive target-specific therapy may provide faster control of severe symptoms, shorten the disease course, and lead to long-lasting disease stability. Among the various novel therapeutic approaches, modulation of targeted receptors by small molecules crossing the blood-brain barrier as well as prevention of aAB binding is of particular interest.
抗体介导的脑炎(AE)与针对神经元表面抗原的致病性自身抗体(aAB)有关,是一组不断增加的疾病,其特征是大脑中的抗神经元自身免疫。AE 患者通常表现为快速进展性脑炎和依赖于靶抗原的特征性疾病症状。目前的治疗包括免疫治疗策略的升级,包括血浆置换、类固醇应用和 B 细胞耗竭。
对于这篇综述,我们检索了 Medline 数据库和谷歌学术,时间范围从 2000 年开始。我们总结了当前的治疗策略,并介绍了靶向特异性干预的新型治疗方法在临床前水平以及针对抗体诱导的病理学的免疫治疗。治疗选择包括靶蛋白的调节、下游途径的干预、抗体修饰和分泌抗体的细胞耗竭。
尽管 AE 中的当前治疗在许多患者中有效,但恢复通常是延长的,并且可能会发生复发和持续的缺陷。特异性免疫治疗结合支持性的靶向治疗可能会更快地控制严重症状、缩短疾病过程并导致长期的疾病稳定。在各种新型治疗方法中,小分子穿过血脑屏障调节靶向受体以及预防 aAB 结合特别有趣。