The immune system and autism spectrum disorder: association and therapeutic challenges

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, affecting communication and behavior. Historically, ASD had been described as a purely psychiatric disorder with genetic factors playing the most critical role. Recently, a growing body of literature has been emphasizing the importance of environmental and immunological factors in its pathogenesis, with the autoimmune process attracting the most attention. This study provides a review of the autoimmune involvement in the pathogenesis of ASD. The microbiome, the representative of the innate immune system in the central nervous system (CNS), plays a critical role in triggering inflammation. Besides, a bidirectional communicational pathway between the CNS and the intestine called the gut-brain-axis is linked to the development of ASD. Moreover, the higher plasma level of pro-inflammatory cytokines in ASD patients and the higher prevalence of autoimmune disorders in the first-degree family members of affected persons are other clues of the immune system involvement in the pathogenesis of ASD. Furthermore, some anti-inflammatory drugs, including resveratrol and palmitoylethanolamide have shown promising effects by relieving the manifestations of ASD. Although considerable advances have been made in elucidating the role of autoimmunity in the ASD pathogenesis, further studies with stronger methodologies are needed to apply the knowledge to the definitive treatment of ASD.

The role of Toll-like receptors and neuroinflammation in Parkinson’s disease

“…In the CNS, there are various resident cell types such as microglia, astrocytes, and oligodendrocytes performing roles as innate immune cells [ 36 ]. The activation of these cells under several conditions can contribute to the secretion of inflammatory cytokines and reactive oxygen species (ROS), leading to neuroinflammation, which might disrupt the blood–brain barrier (BBB) and thereby allow and chemotactically attract several peripheral immune cells such as monocytes, macrophages, neutrophils, and T cells to join the CNS, aggravating the inflammation [ 37 – 39 ]. This inflammation might be triggered due to different CNS infections or sterile aggregation of toxic metabolites and proteins, as seen in neurodegenerative disorders.…”

A molecular framework for autistic experiences: Mitochondrial allostatic load as a mediator between autism and psychopathology

“…Cytokine-stimulated immune cells can also promote HPA axis activation and GC signaling by upregulating the production of corticotrophin-releasing hormone (CRH) in the hypothalamus (181). Of particular relevance, animal models have demonstrated an antagonistic relationship between HPA activity and interleukin 6 (IL-6), which is one of the most consistently upregulated inflammatory markers associated with ELS (204), MDD (209) and ASC (272) that has also been widely implicated in psychological disorders (273). Markedly, recent preclinical studies suggest that neuroimmune-HPA interactions facilitate the neuroinflammatory response to stress.…”

Three Imaging Endophenotypes Characterize Neuroanatomical Heterogeneity of Autism Spectrum Disorder

“…One of the associated genes of the A2 dimension ( DEFB119 ) was previously associated with the pathway of the innate immune system in individuals with ASD. 52 Furthermore, the A2 dimension was overrepresented in the biological pathway of hydrogen peroxide-mediated programmed cell death. Many studies have shown that oxidative stress, partly due to hydrogen peroxide (H 2 O 2 ), is elevated in individuals with ASD.…”