Potential for Early-Life Immune Insult Including Developmental Immunotoxicity in Autism and Autism Spectrum Disorders: Focus on Critical Windows of Immune Vulnerability

Abstract

Early-life immune insults (ELII) including xenobiotic-induced developmental immunotoxicity (DIT) are important factors in childhood and adult chronic diseases. However, prenatal and perinatal environmentally induced immune alterations have yet to be considered in depth in the context of autism and autism spectrum disorders (ASDs). Numerous factors produce early-life-induced immune dysfunction in offspring, including exposure to xenobiotics, maternal infections, and other prenatal-neonatal stressors. Early life sensitivity to ELII, including DIT, results from the heightened vulnerability of the developing immune system to disruption and the serious nature of the adverse outcomes arising after disruption of one-time immune maturational events. The resulting health risks extend beyond infectious diseases, cancer, allergy, and autoimmunity to include pathologies of the neurological, reproductive, and endocrine systems. Because these changes may include misregulation of resident inflammatory myelomonocytic cells in tissues such as the brain, they are a potential concern in cases of prenatal-neonatal brain pathologies and neurobehavioral deficits. Autism and ASDs are chronic developmental neurobehavioral disorders that are on the rise in the United States with prenatal and perinatal environmental factors suspected as contributors to this increase. Evidence for an association between environmentally associated childhood immune dysfunction and ASDs suggests that ELII and DIT may contribute to these conditions. However, it is not known if this linkage is directly associated with the brain pathologies or represents a separate (or secondary) outcome. This review considers the known features of ELII and DIT and how they may provide important clues to prenatal brain inflammation and the risk of autism and ASDs.

Environmental factors associated with autism spectrum disorder: a scoping review for the years 2003–2013

“…According to the reviews based mainly on animal and human clinical studies, early-life immune insults such as toxic substances, food additives or stress may result in a cascade of excitotoxicity in the brain, [197][198][199] and may be related to dysregulation of glutamate neurotransmission. 199,200 This cascade may trigger production of proinflammatory cytokines, resulting in chronic inflammation affecting neurodevelopment.…”

Facteurs environnementaux associés au trouble du spectre de l’autisme : étude de délimitation portant sur les années 2003 à 2013

“…Selon les revues de la littérature basées principalement sur des études cliniques portant sur des animaux et des humains, des accidents immunitaires au début de la vie, comme des substances toxiques, des additifs alimentaires ou le stress, peuvent entraîner une cascade d'excitotoxicité dans le cerveau [197][198][199] et peuvent être liés à une dysrégu lation de la neurotransmission du glutamate 199,200 .…”

Theoretical aspects of autism: Causes—A review

“…In addition, there are critical windows of time during which the fetus is more vulnerable immunologically (Meyer et al, 2006;Dietert and Dietert, 2008). Data reveal that maternal viral infection in the first trimester and bacterial infection in the second trimester are associated with diagnosis of autism in the offspring (Atladóttir et al, 2010).…”