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

Harumi Jyonouchi,Lee Geng,Agnes Cushing-Ruby,Huma Quraishi

doi:10.1186/1742-2094-5-52

Abstract

BackgroundAmong patients with autism spectrum disorders (ASD) evaluated in our clinic, there appears to be a subset that can be clinically distinguished from other ASD children because of frequent infections (usually viral) accompanied by worsening behavioural symptoms and/or loss/decrease in acquired skills. This study assessed whether these clinical features of this ASD subset are associated with atopy, asthma, food allergy (FA), primary immunodeficiency (PID), or innate immune responses important in viral infections.MethodsThis study included the ASD children described above (ASD test, N = 26) and the following controls: ASD controls (N = 107), non-ASD controls with FA (N = 24), non-ASD controls with chronic rhinosinusitis/recurrent otitis media (CRS/ROM; N = 38), and normal controls (N = 43). We assessed prevalence of atopy, asthma, FA, CRS/ROM, and PID. Innate immune responses were assessed by measuring production of proinflammatory and counter-regulatory cytokines by peripheral blood mononuclear cells (PBMCs) in response to agonists of Toll-like receptors (TLRs), with or without pre-treatment of lipopolysaccharide (LPS), a TLR4 agonist.ResultsNon-IgE mediated FA was equally prevalent in both ASD test and ASD control groups, occurring at higher frequency than in the non-ASD controls. Allergic rhinitis, atopic/non-atopic asthma, and atopic dermatitis were equally prevalent among the study groups except for the CRS/ROM group in which non-atopic asthma was more prevalent (52.6%). CRS/ROM and specific polysaccharide antibody deficiency (SPAD) were more prevalent in the ASD test group than in the ASD control, FA, and normal control groups: 23.1% vs. < 5% for CRS/ROS and 19.2% vs. < 1% for SPAD. However, CRS/ROM patients had the highest prevalence of SPAD (34.2%). When compared to ASD and normal case controls, PBMCs from 19 non-SPAD, ASD test group children produced: 1) less IL-1β with a TLR7/8 agonist, less IL-10 with a TLR2/6 agonist, and more IL-23 with a TLR4 agonist without LPS pre-treatment, and 2) less IL-1β with TLR4/7/8 agonists with LPS pre-treatment. These are cytokines associated with the neuro-immune network.ConclusionClinical features of the ASD test group were not associated with atopy, asthma, FA, or PID in our study but may be associated with altered TLR responses mediating neuro-immune interactions.

Highlights

Among patients with autism spectrum disorders (ASD) evaluated in our clinic, there appears to be a subset that can be clinically distinguished from other ASD children because of frequent infections accompanied by worsening behavioural symptoms and/or loss/decrease in acquired skills
chronic rhinosinusitis (CRS) is a major trigger for asthma [12] and, not surprisingly, chronic rhinosinusitis/recurrent otitis media (CRS/ROM) patients were distinguished by a high frequency of atopic and non-atopic asthma as compared to other study groups (Table 2)
Despite frequent antibiosis, which causes GI symptoms by disrupting commensal flora and may subsequently predispose the subjects to food allergy (FA), non-IgE mediated FA (NFA) was not as prevalent in CRS/ROM children as in the ASD children (p = 4.048e-11 by χ2 test) (Table 2). These results indicate that FA is not closely associated with the clinical characteristics of the ASD test group

Summary

Introduction

Among patients with autism spectrum disorders (ASD) evaluated in our clinic, there appears to be a subset that can be clinically distinguished from other ASD children because of frequent infections (usually viral) accompanied by worsening behavioural symptoms and/or loss/decrease in acquired skills. A high prevalence of GI symptoms, which often improve after dietary intervention, has been reported by parents This has led to speculation that there may be a high prevalence of food allergy (FA) in ASD children. Our results revealed increased tumour necrosis factor-α (TNF-α) production against cow's milk protein along with correlating clinical features consistent with NFA [2]. In these ASD children with NFA, we observed excessive production of TNF-α in response to LPS, an agonist of Toll-like receptor 4 (TLR4) [3]

Methods

Results

Discussion

Conclusion