Objectives: A correlation between autism spectrum disorders (ASDs) and gastrointestinal (GI) problems, and a possible link between gluten consumption and ASD have been increasingly reported. Gluten/casein-free diet (GCFD) is often undertaken, with conflicting results. This study aimed at evaluating the distribution of human leukocyte antigen (HLA)-DQ2/DQ8 typing among patients with ASD with GI symptoms, together with its correlation with duodenal histology and response to GCFD. Methods: Between 2002 and 2015 all patients with ASD with GI symptoms referred to our outpatient clinic, displaying clinical, laboratory, or ultrasound findings suggestive of organic disease, underwent endoscopy, celiac disease (CD) serum antibodies testing and HLA-DQ2/DQ8 genotyping. Patients were prescribed a 6-month GCFD, and then clinically reassessed. Results: Among 151 enrolled patients, 134 (89%) were negative for CD-specific antibodies; 72 (48%) were positive for HLA-DQ2/DQ8; and 56 (37%) showed duodenal microscopic inflammation. Clinical improvement was observed in non-CD patients irrespective of the rigorous or partial adherence to the diet, being the difference nonstatistically significant. Response to diet was related to the presence of histological duodenal alterations at baseline (odds ratio 11.323, 95% confidence interval 1.386–92.549 for Marsh 2 pattern), but not to HLA-DQ2/DQ8 positivity (odds ratio 1.120, 95% confidence interval 0.462–2.716). Conclusions: Our data suggest that children with ASD with GI symptoms have a high prevalence of duodenal intraepithelial lymphocytic infiltration, which seems to be linked to a mechanism other than autoimmune response to gluten consumption. Alteration of duodenal histology, but not the HLA-DQ2/DQ8 status, was associated with clinical response to the diet. Address correspondence and reprint requests to Carlo Alessandria, MD, Division of Gastroenterology and Hepatology, Città Della Salute e Della Scienza di Torino Hospital, University of Turin, C.so Bramante 88, 10126 Turin, Italy (e-mail: carloalessandria@libero.it). Received 22 June, 2018 Accepted 22 January, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). The authors report no conflicts of interest. © 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,
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