The role of immune dysfunction in the pathophysiology of autism

Abstract

Autism spectrum disorders (ASD) are a complex group of neurodevelopmental disorders encompassing impairments in communication, social interactions and restricted stereotypical behaviors. Although a link between altered immune responses and ASD was first recognized nearly 40 years ago, only recently has new evidence started to shed light on the complex multifaceted relationship between immune dysfunction and behavior in ASD. Neurobiological research in ASD has highlighted pathways involved in neural development, synapse plasticity, structural brain abnormalities, cognition and behavior. At the same time, several lines of evidence point to altered immune dysfunction in ASD that directly impacts some or all these neurological processes. Extensive alterations in immune function have now been described in both children and adults with ASD, including ongoing inflammation in brain specimens, elevated pro-inflammatory cytokine profiles in the CSF and blood, increased presence of brain-specific auto-antibodies and altered immune cell function. Furthermore, these dysfunctional immune responses are associated with increased impairments in behaviors characteristic of core features of ASD, in particular, deficits in social interactions and communication. This accumulating evidence suggests that immune processes play a key role in the pathophysiology of ASD. This review will discuss the current state of our knowledge of immune dysfunction in ASD, how these findings may impact on underlying neuro-immune mechanisms and implicate potential areas where the manipulation of the immune response could have an impact on behavior and immunity in ASD.

Endocannabinoid Signaling in Autism

“…Finally, neuroinflammation is also a frequent finding in postmortem brains of autistic individuals [64,65]. It may represent a nonspecific consequence of insufficient neurite pruning and abnormal wiring of neural networks, resulting in elevated oxidative stress (possibly a common feature shared by several neurodevelopmental disorders) [66], but it could also stem from a broader immune dysfunction which, together with gastrointestinal disturbances and recurrent infections, collectively qualifies ASD as a systemic disorder [67][68][69][70][71].…”

Prenatal immune activation causes hippocampal synaptic deficits in the absence of overt microglia anomalies

“…These disorders have also been associated with altered microglia functions and associated neuroinflammatory changes (Arion et al, 2007;Doorduin et al, 2009;Fung et al, 2014;Morgan et al, 2010;Tetreault et al, 2012;van Berckel et al, 2008;Volk et al, 2015). It remains elusive, however, whether and to what extent such microglial abnormalities may be responsible for the development of synaptic deficits as, for example, seen in schizophrenia or autism Onore et al, 2012). Against these backgrounds, the present study aimed at exploring potential associations between impaired synaptic development and microglial abnormalities in a model of prenatal immune activation with relevance to neurodevelopmental disorders.…”

Os efeitos da música em biomarcadores de estresse, imunológicos e comportamentais em portadores do espectro autista

“…Spiroski et al 12 relatam a hipótese de que os baixos níveis de IgA são frequentemente encontrados em crianças com TEA, quando comparados ao seus pais, bem como aos seus irmãos e irmãs saudáveis provenientes dos mesmos genitores. Segundo Onore, Careaga e Ashwooda, 7 as respostas imunitárias disfuncionais estão associadas a maiores transtornos nos comportamentos característi-cos do TEA, como déficits nas interações sociais e na comunicação.…”

“…5,6 Evidências também foram encontradas na relação entre os marcadores bioquímicos e as estereotipias comportamentais, de movimento, e também na capacidade de atenção e comunicação interpessoal, sendo esta última considerada um dos principais fatores estressores que desencadeiam o comportamento autista. 7 Além da resposta imunológica alterada em indiví-duos com TEA, existem estudos que buscaram verificar a relação entre disfunções celulares e o desenvolvimento do TEA, considerando a avaliação celular como um biomarcador de saúde nesses indivíduos. Nos referidos estudos, são destacados o estresse oxidativo, disfunções mitocondriais e os danos celulares associados ao autismo.…”