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免疫功能障碍和自身免疫作为自闭症谱系障碍的病理机制

Immune Dysfunction and Autoimmunity as Pathological Mechanisms in Autism Spectrum Disorders.

作者信息

Hughes Heather K, Mills Ko Emily, Rose Destanie, Ashwood Paul

机构信息

Department of Medical Microbiology and Immunology, University of California, Davis, Davis, CA, United States.

MIND Institute, UC Davis Medical Center, Sacramento, CA, United States.

出版信息

Front Cell Neurosci. 2018 Nov 13;12:405. doi: 10.3389/fncel.2018.00405. eCollection 2018.

Abstract

Autism spectrum disorders (ASD) are a group of heterogeneous neurological disorders that are highly variable and are clinically characterized by deficits in social interactions, communication, and stereotypical behaviors. Prevalence has risen from 1 in 10,000 in 1972 to 1 in 59 children in the United States in 2014. This rise in prevalence could be due in part to better diagnoses and awareness, however, these together cannot solely account for such a significant rise. While causative connections have not been proven in the majority of cases, many current studies focus on the combined effects of genetics and environment. Strikingly, a distinct picture of immune dysfunction has emerged and been supported by many independent studies over the past decade. Many players in the immune-ASD puzzle may be mechanistically contributing to pathogenesis of these disorders, including skewed cytokine responses, differences in total numbers and frequencies of immune cells and their subsets, neuroinflammation, and adaptive and innate immune dysfunction, as well as altered levels of immunoglobulin and the presence of autoantibodies which have been found in a substantial number of individuals with ASD. This review summarizes the latest research linking ASD, autoimmunity and immune dysfunction, and discusses evidence of a potential autoimmune component of ASD.

摘要

自闭症谱系障碍(ASD)是一组异质性神经疾病,具有高度变异性,临床特征为社交互动、沟通及刻板行为方面的缺陷。其患病率已从1972年的万分之一上升至2014年美国每59名儿童中有1例患病。患病率的上升部分可能归因于诊断水平的提高和认知度的提升,然而,这些因素并不能完全解释如此显著的增长。虽然在大多数情况下尚未证实因果联系,但目前许多研究聚焦于遗传与环境的综合作用。引人注目的是,过去十年中出现了一种明显的免疫功能障碍情况,并得到了许多独立研究的支持。免疫与自闭症谱系障碍难题中的许多因素可能在机制上促成了这些疾病的发病过程,包括细胞因子反应失衡、免疫细胞及其亚群总数和频率的差异、神经炎症、适应性和先天性免疫功能障碍,以及免疫球蛋白水平的改变和自身抗体的存在,在大量自闭症谱系障碍患者中都发现了这些情况。本综述总结了将自闭症谱系障碍、自身免疫和免疫功能障碍联系起来的最新研究,并讨论了自闭症谱系障碍潜在自身免疫成分的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5abd/6242891/fac6ca38573c/fncel-12-00405-g0001.jpg

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