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Horvath, K.1; Rabsztyn, A.1; Chey, W. K.2; Perman, J. A.1
1Department of Pediatrics, University of Maryland School of Medicine, Baltimore, 2Department of Internal Medicine, University of Rochester, Rochester, United States
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Introduction: Recently published papers indicate that significant percentage of the children with autism spectrum disorder (ASD) have abnormalities in the digestive tract. Among the reported duodenal abnormalities are hypersecretory response to exogenous secretin, which is suggestive of an up-regulation of pancreatic secretin receptors and Paneth cell hyperplasia. Animal studies showed that the absence of pancreatic enzymes resulted in duodenal Paneth cell hyperplasia. The aims of this study were to assess the secretin release and analyze the content of Paneth cells in children with ASD.
Methods: Duodenal acidification study (0.05M HCl)was performed during upper gastrointestinal endoscopies on children with ASD and age-matched controls. The pre- and post-acidification (10 minutes) serum secretin concentrations were measured by RIA. Intestinal biopsy slides were stained with anti-lysozyme, anti-defensin and phospholipase antibodies. The intensity of the staining was evaluated with “Image J Analysis” program. The lysozyme content of biopsy homogenate, blood, urine and duodenal washing fluid was measured by ELISA.
Results: There was no significant difference in the basal and post-acidification secretin concentrations between the ASD and control children (P>0.05). The intensity of lysozyme staining in the Paneth cells was visibly stronger and the image analysis confirmed a significantly higher concentration of lysozyme in the Paneth cell granules of children with ASD. It was further confirmed with a significantly higher lysozyme content in the biopsy homogenate. While there was higher (P <0.05) lysozyme content in the intestinal washing fluid and urine in children with ASD there was no difference in the blood lysozyme concentrations between the two groups. The intensity of staining for defensin and phospholipase was not different in the two groups.
Conclusion: There was no decreased secretin release in children with autism. Therefore the increased response to exogenous secretin is more likely due to a dysfunction in the cephalic phase of digestion then to a defect in duodenal secretin production and release. The increased lysozyme secretion by the duodenal Paneth cells is probably triggered by microenvironmental factors (infectious agents, autoimmune process) not the consequence of a decreased secretin production. The mechanism of hypersecretory response to secretin and the hyperplasia of Paneth cells warrants further investigations, which may contribute to the understanding of the pathomechanism of ASD.
© 2004 Lippincott Williams & Wilkins, Inc.
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