This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Celiac sprue is a chronic inflammatory response to dietary gluten that is characterized by clinical diarrhea, intestinal villous atrophy, and the circulation of antibodies against gliadin and transglutaminase 2. The initiation of the immune response to ingested gluten requires that luminal gluten peptides be transported intact across the mucosal epithelium, but the transepithelial translocation of an immunogenic gluten peptide has not been demonstrated in vivo. We have identified and characterized a condition of simian gluten sensitive enteropathy (GSE) in captive juvenile rhesus macaques. Affected animals present with chronic diarrhea, and exhibit intestinal lesions and anti-gliadin antibodies (but not anti-transglutaminase antibodies) when fed a gluten-containing diet. Removal of dietary gluten reversed the clinical, histological, and serological hallmarks of enteropathy in an affected animal, while reintroduction of dietary gluten caused rapid relapse. An orally dosed, isotope-labeled 33-mer gluten peptide was detected in the plasma of an affected animal when in remission and during active enteropathy, but was not detected in the plasma of a similarly- dosed healthy control animal. The GSE rhesus macaque affords a model system for studying the relationship between intestinal permeability and gluten sensitive enteropathy.
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