Abstract：
Autoimmune encephalitis (AE) is a group of inflammatory conditions that can associate with the presence of antibodies directed to neuronal intracellular, or cell surface antigens. These disorders are increasingly recognized as an important differential diagnosis of infectious encephalitis and of other common neuropsychiatric conditions. Autoantibody diagnostics plays a pivotal role for accurate diagnosis of AE, which is of utmost importance for the prompt recognition and early treatment. Several AE subgroups can be identified, either according to the prominent clinical phenotype, presence of a concomitant tumor, or type of neuronal autoantibody, and recent diagnostic criteria have provided important insights into AE classification. Antibodies to neuronal intracellular antigens typically associate with paraneoplastic neurological syndromes and poor prognosis, whereas antibodies to synaptic/neuronal cell surface antigens characterize many AE subtypes that associate with tumors less frequently, and that are often immunotherapy-responsive. In addition to the general features of AE, we review current knowledge on the pathogenic mechanisms underlying these disorders, focusing mainly on the potential role of neuronal antibodies in the most frequent conditions, and highlight current theories and controversies. Then, we dissect the crucial aspects of the laboratory diagnostics of neuronal antibodies, which represents an actual challenge for both pathologists and neurologists. Indeed, this diagnostics entails technical difficulties, along with particularly interesting novel features and pitfalls. The novelties especially apply to the wide range of assays used, including specific tissue-based and cell-based assays. These assays can be developed in-house, usually in specialized laboratories, or are commercially available. They are widely used in clinical immunology and in clinical chemistry laboratories, with relevant differences in analytic performance. Indeed, several data indicate that in-house assays could perform better than commercial kits, notwithstanding that the former are based on non-standardized protocols. Moreover, they need expertise and laboratory facilities usually unavailable in clinical chemistry laboratories. Together with the data of the literature, we critically evaluate the analytical performance of the in-house vs commercial kit-based approach. Finally, we propose an algorithm aimed at integrating the present strategies of the laboratory diagnostics in AE for the best clinical management of patients with these disorders.
摘要：
自身免疫性脑炎（AE）是一组炎性病症，可以与针对神经元细胞内的抗体的存在有关，或细胞表面抗原。这些疾病越来越被认为是感染性脑炎和其他常见神经精神疾病的重要鉴别诊断。自身抗体诊断对AE的准确诊断起着举足轻重的作用,这对于及时识别和早期治疗至关重要。可以识别几个AE亚组，根据突出的临床表型，伴随肿瘤的存在，或神经元自身抗体的类型，和最近的诊断标准为AE分类提供了重要的见解。神经元细胞内抗原的抗体通常与副肿瘤神经综合征和不良预后有关。而针对突触/神经元细胞表面抗原的抗体表征了许多与肿瘤相关频率较低的AE亚型，通常对免疫疗法有反应。除了AE的一般特征外，我们回顾了有关这些疾病的致病机制的最新知识，主要关注神经元抗体在最常见条件下的潜在作用，并强调当前的理论和争议。然后，我们剖析了神经元抗体实验室诊断的关键方面，这对病理学家和神经学家来说都是一个实际的挑战。的确,这种诊断需要技术上的困难，以及特别有趣的新颖特征和陷阱。这些新颖性特别适用于广泛使用的检测方法，包括特定的基于组织和基于细胞的测定。这些检测方法可以在内部开发,通常在专业实验室，或者是商业上可用的。它们广泛用于临床免疫学和临床化学实验室，在分析性能方面存在相关差异。的确,一些数据表明，内部检测可以比商业试剂盒更好，尽管前者是基于非标准化协议。此外，他们需要临床化学实验室通常无法获得的专业知识和实验室设施。结合文献的数据，我们批判性地评估内部与基于商业套件的方法的分析性能。最后,我们提出了一种算法,旨在整合目前AE实验室诊断的策略,以便为这些疾病的患者提供最佳的临床治疗.
