Impact of innate immunity in a subset of children with autism spectrum disorders: a case control study

Area of Science:

• Neuroimmunology
• Autism Spectrum Disorders (ASD)
• Innate Immunity

Background:

• A distinct subset of children with autism spectrum disorder (ASD) presents with frequent infections, particularly viral, coinciding with behavioral regression or skill loss.
• This clinical presentation suggests a potential link between immune system dysregulation and specific ASD phenotypes.
• The study aimed to investigate associations between these ASD features and common allergic conditions, primary immunodeficiencies (PID), and innate immune responses.

Purpose of the Study:

• To determine if a specific subset of ASD patients with frequent infections and behavioral changes are associated with atopy, asthma, food allergy (FA), or PID.
• To assess innate immune responses in these ASD patients by analyzing cytokine production from peripheral blood mononuclear cells (PBMCs).
• To explore the role of Toll-like receptor (TLR) signaling in the neuro-immune interactions within this ASD subgroup.

Main Methods:

• Compared prevalence of atopy, asthma, FA, chronic rhinosinusitis/recurrent otitis media (CRS/ROM), and PID in an ASD test group (N=26) against various control groups (ASD controls, non-ASD controls with FA, non-ASD controls with CRS/ROM, normal controls).
• Assessed innate immune responses by stimulating PBMCs with TLR agonists and measuring pro-inflammatory and counter-regulatory cytokine production.
• Utilized lipopolysaccharide (LPS), a TLR4 agonist, with and without pre-treatment to evaluate TLR pathway functionality.

Main Results:

• Non-IgE mediated food allergy (FA) was more prevalent in ASD test and control groups compared to non-ASD controls.
• Chronic rhinosinusitis/recurrent otitis media (CRS/ROM) and specific polysaccharide antibody deficiency (SPAD) were significantly more prevalent in the ASD test group.
• PBMCs from the ASD test group (non-SPAD) showed altered cytokine production (reduced IL-1β, IL-10; increased IL-23) in response to TLR agonists, indicating dysregulated neuro-immune signaling.

Conclusions:

• The specific clinical features in the studied ASD subset were not directly linked to atopy, asthma, FA, or PID.
• Altered innate immune responses, specifically involving TLR pathways and subsequent cytokine production, are potentially associated with the observed clinical phenotype in this ASD group.
• These findings highlight a possible role for neuro-immune dysregulation in a subset of autism spectrum disorder patients.