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


METHODS
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, beta-lactoglobulin, and alpha-lactoalbumin), gliadin, and soy.


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


CONCLUSIONS
A high prevalence of elevated TNF-alpha/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.
Jyonouchi
Harumi
H
Department of Pediatrics, Division of Pulmonary, Allergy/Immunology, and Infectious Diseases, New Jersey Medical School/UMDNJ, 185 South Orange Avenue, Newark, NJ 07101-1709, USA. jyanouha@umdnj.edu
Geng
Lee
L
Ruby
Agnes
A
Reddy
Chitra
C
Zimmerman-Bier
Barbie
B
D001321:Autistic Disorder / Q000150:complications / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003248:Constipation / Q000209:etiology; D016207:Cytokines / Q000096:biosynthesis*; D003967:Diarrhea / Q000209:etiology; D005260:Female; D005504:Food Analysis; D006801:Humans; D007223:Infant; D008297:Male; D008894:Milk Proteins / Q000009:adverse effects* / Q000032:analysis / Q000276:immunology
D016207:Cytokines; D008894:Milk Proteins