Original Article
Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders

https://doi.org/10.1016/j.jpeds.2005.01.027Get rights and content

Objective

To evaluate an association between cytokine production with common dietary proteins as a marker of non-allergic food hypersensitivity (NFH) and gastrointestinal (GI) symptoms in young children with autism spectrum disorders (ASD).

Study design

Peripheral blood mononuclear cells (PBMCs) were obtained from 109 ASD children with or without GI symptoms (GI [+] ASD, N = 75 and GI (−) ASD, N = 34], from children with NFH (N = 15), and control subjects (N = 19). Diarrhea and constipation were the major GI symptoms. We measured production of type 1 T-helper cells (Th1), type 2 T-helper cells (Th2), and regulatory cytokines by PBMCs stimulated with whole cow's milk protein (CMP), its major components (casein, β-lactoglobulin, and α-lactoalbumin), gliadin, and soy.

Results

PBMCs obtained from GI (+) ASD children produced more tumor necrosis factor-α (TNF-α)/interleukin-12 (IL-12) than those obtained from control subjects with CMP, β-lactoglobulin, and α-lactoalbumin, irrespective of objective GI symptoms. They also produced more TNF-α with gliadin, which was more frequently observed in the group with loose stools. PBMCs obtained from GI (−) ASD children produced more TNF-α/IL-12 with CMP than those from control subjects, but not with β-lactoglobulin, α-lactoalbumin, or gliadin. Cytokine production with casein and soy were unremarkable.

Conclusion

A high prevalence of elevated TNF-α/IL-12 production by GI (+) ASD PBMCs with CMP and its major components indicates a role of NFH in GI symptoms observed in children with ASD.

Section snippets

Study Subjects

The study subjects included children (aged 1-10 years) in Tanner stage 1. Children with ASD were recruited from those referred to the Autism Center at the New Jersey Medical School, University of Medicine and Dentistry of NJ, Newark, NJ. ASD diagnosis was made or ascertained by means of the Diagnostic and Statistical Manual of Mental Disorders-IV, the International Classification of Diseases-10 criteria, or both, the Autism Diagnostic Interview-Revised, and Autism Diagnostic Observational

Cytokine Production in Response to Common DPs

Our findings in cytokine production with a stimulus of each DP tested were:

  • 1)

    CMP: PBMCs from both GI (+) and GI (−) ASD children produced more TNF-α and IL-12 than those from control subjects. NFH PBMCs produced more IFN-γ, TNF-α, IL-10, and IL-12 than those from control subjects (Figure 1A).

  • 2)

    Casein: Cytokine production by PBMCs was minimal and did not differ among the study groups (data not shown).

  • 3)

    β-Lactoglobulin: PBMCs from GI (+) ASD children, but not from GI (−) children, produced more TNF-α

Discussion

Our results revealed a high prevalence (>70%) of cellular immune reactivity to CMP and its major components in GI (+) ASD children when positive reactivity is defined as >CM + 1SD production of TNF-α, IL-12, or both with CMP, β-lactoglobulin (a major component of CMP), or both. Such cellular reactivity was less remarkable with gliadin. Our findings indicate a possible role of NFH against CMPs in GI symptoms observed in children with ASD.

GI symptoms are frequently observed in children with ASD,

References (17)

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Supported by the Jonty Foundation (St. Paul, Minnesota).

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