Careaga Milo, Ashwood Paul
Department of Medical Microbiology and Immunology and the M.I.N.D. Institute, University of California at Davis, Davis, CA, USA.
Methods Mol Biol. 2012;934:219-40. doi: 10.1007/978-1-62703-071-7_12.
Autism spectrum disorders (ASD) are complex and heterogeneous with a spectrum of diverse symptoms. Mounting evidence from a number of disciplines suggests a link between immune function and ASD. Although the causes of ASD have yet to be identified, genetic studies have uncovered a host of candidate genes relating to immune regulation that are altered in ASD, while epidemiological studies have shown a relationship with maternal immune disturbances during pregnancy and ASD. Moreover, decades of research have identified numerous systemic and cellular immune abnormalities in individuals with ASD and their families. These include changes in immune cell number, differences in cytokine and chemokine production, and alterations of cellular function at rest and in response to immunological challenge. Many of these changes in immune responses are associated with increasing impairment in behaviors that are core features of ASD. Despite this evidence, much remains to be understood about the precise mechanism by which the immune system alters neurodevelopment and to what extent it is involved in the pathogenesis of ASD. With estimates of ASD as high as 1% of children, ASD is a major public health issue. Improvements in our understanding of the interactions between the nervous and immune system during early neurodevelopment and how this interaction is different in ASD will have important therapeutic implications with wide ranging benefits.
自闭症谱系障碍(ASD)复杂多样,症状各异。多个学科越来越多的证据表明免疫功能与ASD之间存在联系。尽管ASD的病因尚未明确,但基因研究已发现许多与免疫调节相关的候选基因在ASD中发生了改变,而流行病学研究则显示孕期母亲的免疫紊乱与ASD有关。此外,数十年的研究已确定ASD患者及其家族存在众多全身性和细胞免疫异常。这些异常包括免疫细胞数量的变化、细胞因子和趋化因子产生的差异,以及静息状态下和免疫刺激反应时细胞功能的改变。免疫反应中的许多此类变化都与ASD核心症状行为的损害加剧有关。尽管有这些证据,但免疫系统改变神经发育的确切机制以及它在ASD发病机制中的参与程度仍有待深入了解。据估计,ASD在儿童中的发病率高达1%,是一个重大的公共卫生问题。增进我们对早期神经发育过程中神经与免疫系统相互作用的理解,以及了解这种相互作用在ASD中有何不同,将具有重要的治疗意义,并带来广泛益处。