Gluten Sensitivity Linked to Autism
A subset of children with autism have increased
immune reactivity to gluten, but the mechanism of this increased
reactivity appears to be distinct from that involved with celiac
disease, new research shows.
The results also indicated an association between elevated antibodies to gluten proteins and the presence of gastrointestinal (GI) symptoms in the affected children.
"There is evidence that immune system abnormalities are associated with symptoms in a substantial number of individuals with autism," senior author Armin Alaedini, PhD, assistant professor of medical sciences in the Department of Medicine and the Institute of Human Nutrition at Columbia University Medical Center, New York City, told Medscape Medical News.
"In addition, several studies have evaluated gastrointestinal symptoms and defects in GI barrier function in affected patients. Some have pointed to higher frequency of celiac disease, family history of celiac disease, or elevated antibody to gluten among autistic children, but these studies have been inconsistent about such associations," Dr. Alaedini said.
The study was published online June 18 in PLoS One.
Growing Popularity of Gluten-Free Diets
Diets that exclude gluten are increasingly popular in the autism community, but their effectiveness has not been proven in controlled and blinded studies.
In the current study, Dr. Alaedini and his team analyzed serologic and genetic markers of celiac disease and gluten sensitivity in 37 children diagnosed with autism according to both the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview, Revised (ADI-R) as well as in 27 of their unaffected siblings and 76 age-matched unrelated healthy control individuals.
The blood samples were tested for antibodies to tissue transglutaminase, a sensitive and specific marker of celiac disease, as well as antibodies to gliadin.
The children with autism were also genotyped for celiac disease associated HLA-DQ2 and HLA-DQ8 alleles.
The analysis showed that the children with autism had significantly higher levels of IgG antibody to gliadin compared with unrelated healthy controls individuals (P < .01). The IgG levels were also higher compared with the unaffected siblings but did not reach statistical significance.
The researchers also found that the IgG antigliadin antibody response was significantly greater in the autistic children with GI symptoms in comparison to those without GI symptoms (P < .01).
There was no difference in IgA response to gliadin among the 3 groups.
Additionally, levels of celiac disease–specific serologic markers, for example, antibodies to deamidated gliadin and TG2, did not differ between patients and control individuals.
Nor was an association between increased antigliadin antibody and presence of HLA-DQ2 and -DQ8 observed.
Little Clinical Relevance Yet
The findings have little relevance to bedside practice at the moment, Dr. Alaedini said.
"It would be too early to talk about medical advice or treatment resulting directly from this study. Also, the findings need to be confirmed in larger cohorts."
He added that the observations from this study point to immunologic or intestinal barrier abnormalities and their association with GI symptoms in autism.
"Having a clearer understanding of the immunologic differences in the affected children can give us novel clues about the mechanism of autism, such as the potential involvement of immune-mediated pathways. These clues, in turn, may lead to new treatments that, for example, target those specific immune pathways," Dr. Alaedini noted.
"In addition, characterization of the target gluten molecules in the observed antibody response may offer biomarkers to identify a subset of patients that would respond to certain treatment strategies."
Another Piece of the Puzzle
Commenting on the study, Dan Coury, MD, medical director of the Autism Speaks Autism Treatment Network and professor of pediatrics and psychiatry in the College of Medicine at the Ohio State University, Columbus, said the findings provide additional information to what is currently known about GI problems in autism.
"The investigators found increased levels of an antibody to gluten, but not the abnormalities that are seen with celiac disease which is caused by gluten. They also found these antibodies increased more in those with autism and GI problems than in those with autism alone. These antibodies were significantly increased compared to healthy controls, but not significantly different from unaffected siblings. While the IgG antibodies were higher, the IgA antibodies were not," he told Medscape Medical News.
"In this case," Dr. Coury continued, "IgA antibodies are a sign of immune function of the gut mucosa, while IgG antibodies are a sign of the body having an overall immune response, for example, they can indicate a person's immunity to something such as chickenpox."
The findings pose additional questions, he added.
"The high IgG suggests that without high IgA, what we are seeing may not be related to current GI gluten problems but some past exposure. This would also fit with the fact that there were no abnormalities typically seen in celiac disease.
"It might also mean that this IgG antigliadin antibody isn't actually
an antibody to gliadin. It might be an antibody that reacts with
gliadin but actually is produced by the body to react to something
else," he said.
Dr. Coury noted that because immune abnormalities have been seen in autism, it may be another part of the puzzle that needs to be solved.
"By themselves, antigliadin antibodies do not mean disease. They are part of the whole puzzle. When they occur with other abnormalities and with symptoms, we begin to get a clearer picture. As the authors note, these findings deserve further study. It may be that this will help identify a subgroup of individuals with autism who might benefit from a specific treatment someday, when we have a better understanding of just what is going on here."
The study was funded by the US Department of Defense. Dr. Alaedini and Dr. Coury report no relevant financial relationships.
PLoS One. Published online June 18, 2013. Full article
The results also indicated an association between elevated antibodies to gluten proteins and the presence of gastrointestinal (GI) symptoms in the affected children.
"There is evidence that immune system abnormalities are associated with symptoms in a substantial number of individuals with autism," senior author Armin Alaedini, PhD, assistant professor of medical sciences in the Department of Medicine and the Institute of Human Nutrition at Columbia University Medical Center, New York City, told Medscape Medical News.
"In addition, several studies have evaluated gastrointestinal symptoms and defects in GI barrier function in affected patients. Some have pointed to higher frequency of celiac disease, family history of celiac disease, or elevated antibody to gluten among autistic children, but these studies have been inconsistent about such associations," Dr. Alaedini said.
The study was published online June 18 in PLoS One.
Growing Popularity of Gluten-Free Diets
Diets that exclude gluten are increasingly popular in the autism community, but their effectiveness has not been proven in controlled and blinded studies.
In the current study, Dr. Alaedini and his team analyzed serologic and genetic markers of celiac disease and gluten sensitivity in 37 children diagnosed with autism according to both the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview, Revised (ADI-R) as well as in 27 of their unaffected siblings and 76 age-matched unrelated healthy control individuals.
The blood samples were tested for antibodies to tissue transglutaminase, a sensitive and specific marker of celiac disease, as well as antibodies to gliadin.
The children with autism were also genotyped for celiac disease associated HLA-DQ2 and HLA-DQ8 alleles.
The analysis showed that the children with autism had significantly higher levels of IgG antibody to gliadin compared with unrelated healthy controls individuals (P < .01). The IgG levels were also higher compared with the unaffected siblings but did not reach statistical significance.
The researchers also found that the IgG antigliadin antibody response was significantly greater in the autistic children with GI symptoms in comparison to those without GI symptoms (P < .01).
There was no difference in IgA response to gliadin among the 3 groups.
Additionally, levels of celiac disease–specific serologic markers, for example, antibodies to deamidated gliadin and TG2, did not differ between patients and control individuals.
Nor was an association between increased antigliadin antibody and presence of HLA-DQ2 and -DQ8 observed.
Little Clinical Relevance Yet
The findings have little relevance to bedside practice at the moment, Dr. Alaedini said.
"It would be too early to talk about medical advice or treatment resulting directly from this study. Also, the findings need to be confirmed in larger cohorts."
He added that the observations from this study point to immunologic or intestinal barrier abnormalities and their association with GI symptoms in autism.
"Having a clearer understanding of the immunologic differences in the affected children can give us novel clues about the mechanism of autism, such as the potential involvement of immune-mediated pathways. These clues, in turn, may lead to new treatments that, for example, target those specific immune pathways," Dr. Alaedini noted.
"In addition, characterization of the target gluten molecules in the observed antibody response may offer biomarkers to identify a subset of patients that would respond to certain treatment strategies."
Another Piece of the Puzzle
Commenting on the study, Dan Coury, MD, medical director of the Autism Speaks Autism Treatment Network and professor of pediatrics and psychiatry in the College of Medicine at the Ohio State University, Columbus, said the findings provide additional information to what is currently known about GI problems in autism.
"The investigators found increased levels of an antibody to gluten, but not the abnormalities that are seen with celiac disease which is caused by gluten. They also found these antibodies increased more in those with autism and GI problems than in those with autism alone. These antibodies were significantly increased compared to healthy controls, but not significantly different from unaffected siblings. While the IgG antibodies were higher, the IgA antibodies were not," he told Medscape Medical News.
"In this case," Dr. Coury continued, "IgA antibodies are a sign of immune function of the gut mucosa, while IgG antibodies are a sign of the body having an overall immune response, for example, they can indicate a person's immunity to something such as chickenpox."
The findings pose additional questions, he added.
"The high IgG suggests that without high IgA, what we are seeing may not be related to current GI gluten problems but some past exposure. This would also fit with the fact that there were no abnormalities typically seen in celiac disease.
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Dr. Coury noted that because immune abnormalities have been seen in autism, it may be another part of the puzzle that needs to be solved.
"By themselves, antigliadin antibodies do not mean disease. They are part of the whole puzzle. When they occur with other abnormalities and with symptoms, we begin to get a clearer picture. As the authors note, these findings deserve further study. It may be that this will help identify a subgroup of individuals with autism who might benefit from a specific treatment someday, when we have a better understanding of just what is going on here."
The study was funded by the US Department of Defense. Dr. Alaedini and Dr. Coury report no relevant financial relationships.
PLoS One. Published online June 18, 2013. Full article
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