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Children with autism may have elevated immune response to gluten
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Children with autism displayed increased immune reactivity to gluten proteins compared with developmentally healthy children, recent findings suggest. The increased immunoglobulin G antibody response appeared to be related to gastrointestinal symptoms commonly found in children afflicted by the disorder, but there was no connection to celiac disease.
"It should be noted that the increased antibody response to gluten does not necessarily indicate sensitivity to gluten or any disease-causing role for the antibodies in the context of autism," study researcher Armin Alaedini, PhD, assistant professor of medical sciences at Columbia University, said in an interview. "But gaining a better understanding of it may yield novel clues about autism or offer biomarkers to identify a subset of patients that would respond to certain treatment strategies."
Armin Alaedini*
Alaedini and colleagues studied blood samples and medical records of 140 children, including 37 with autism, 27 of their unaffected siblings, and 76 unrelated healthy controls. All children with autism in the study had met criteria based on the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview–Revised. The researchers tested serum specimens for antibodies to the gliadin class of proteins, and children with autism were genotyped for HLA-DQ2 and HLA-DQ8, the two primary gene alleles strongly associated with celiac disease.
Study results indicated that children with autism had significantly higher levels of IgG antibody to gliadin vs. healthy controls (P<.01). Children with autism also had higher antibody levels compared with their unaffected siblings, but the difference was not significant. Autistic children with gastrointestinal symptoms displayed significantly greater anti-gliadin antibody response vs. autistic children without gastrointestinal symptoms (P<.01).
The researchers observed no relationship between gluten sensitivity and specific serologic markers of celiac disease or the presence of the HLA-DQ2 or HLA-DQ8.
According to Alaedini and colleagues, damage to the intestinal epithelial barrier in children with autism may cause intestinal barrier dysfunction, exposing the immune system to partially digested gluten. The increased exposure may result in the heightened immune response observed in children with autism.
Future research should focus on the elevated immune response to gluten as a possible source of biomarkers for a subset of children with autism, the researchers added.
*Photo courtesy of Columbia Technology Ventures
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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W. David Lohr, MD
The recent study by Lau and colleagues is one of several recent research efforts to understand the role of the gastrointestinal (GI) and immune systems in autism. The study finds that a subset of children with autism has increased immune reactivity to the dietary protein gluten. In those children with autism who also had GI symptoms, the levels of immune activity were higher.
The findings are intriguing and join a list of links between autism and the GI and immune systems. A recent study reports that 23% of all cases of autism may result from the presence of maternal antibodies that interfere with fetal brain development during pregnancy (Braunschweig and colleagues). These immune abnormalities in autism may lead to lifelong changes in the brains of individuals, since signs of excessive microglial activation are seen in multiple brain regions in young adult subjects with autism spectrum disorder (Suzuki and colleagues). Also, GI barrier functions in patients in autism are important because autistic children have significantly fewer of the three critical types of gut bacteria compared with normal control individuals (Kang and colleagues).
In the study by Lau and colleagues, the findings involve immunoglobulin G (IgG), which is a general measure of overall immune status. Possible explanations for the findings include past exposure to dietary gluten or cross reactivity to similar proteins. IgA levels are not increased, which suggests current gut mucosa immune function is not involved.
The study is cautious and balanced in its approach and its findings are also important in what they do not tell us about the GI system in autism. The mechanism of this enhanced immune response to gliadin is separate from that seen in celiac disease. The study does not indicate a link between celiac disease and autism and can’t be used to judge the effect of a gluten-free diet in autism.
The strengths of the study include its use of a national database, stringent diagnostic methods for autism using the ADOS and ADI and use of two control groups. The findings may represent important biomarkers in a subset of children with autism, and elevated IgG may be seen in up to 20% of those with the disorder. The next step would be replication in larger studies, and future treatment may involve targeted treatment at IgG pathways in a subset of patients.
For more information:
Braunschweig D. Transl Psychiatry. 2013;doi:10.1038/tp.2013.50.
Suzuki K. JAMA Psychiatry. 2013;70:49-58.
Kang DW. PLoS One. 2013;doi:10.1371/journal.pone.0068322.
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