NON-HUMAN PRIMATE MODEL FOR GLUTEN-SENSITIVE ENTEROPATHY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 面筋敏感性在人类中很普遍。例如，在乳糜泻患者中，对饮食面筋的炎症反应会导致肠病、吸收不良、抗面筋和转谷氨酰胺酶2的循环抗体以及腹泻等临床症状。对表现出人类面筋敏感性的动物模型的基础和翻译研究的需求越来越大。使用基于酶联免疫吸附试验的抗体检测方法，我们筛选了一组圈养猕猴，这些猕猴患有非传染性来源的慢性腹泻，以估计面筋敏感性的发生率。选择一只抗醇溶蛋白抗体升高的动物和一组对照动物，通过交替的无面筋饮食和面筋挑战进行广泛的研究。我们进行了临床和组织学盲法评估，以寻找面筋敏感性的证据。当喂食含面筋的食物时，对面筋敏感的猕猴表现出乳糜泻的症状和体征，包括慢性腹泻、脂肪吸收不良、肠道病变和抗醇溶蛋白抗体。无麸质饮食逆转了这些临床、组织学和血清学特征，而重新引入饮食面筋会导致迅速复发。对面筋敏感的恒河猴可能是研究乳糜泻发病机制和治疗的一个有吸引力的资源。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Gluten sensitivity is widespread among humans. For example, in celiac disease patients, an inflammatory response to dietary gluten leads to enteropathy, malabsorption, circulating antibodies against gluten and transglutaminase 2, and clinical symptoms such as diarrhea. There is a growing need in fundamental and translational research for animal models that exhibit aspects of human gluten sensitivity. Using ELISA-based antibody assays, we screened a population of captive rhesus macaques with chronic diarrhea of non-infectious origin to estimate the incidence of gluten sensitivity. A selected animal with elevated anti-gliadin antibodies and a matched control were extensively studied through alternating periods of gluten-free diet and gluten challenge. Blinded clinical and histological evaluations were conducted to seek evidence for gluten sensitivity. When fed with a gluten-containing diet, gluten-sensitive macaques showed signs and symptoms of celiac disease including chronic diarrhea, malabsorptive steatorrhea, intestinal lesions and anti-gliadin antibodies. A gluten-free diet reversed these clinical, histological and serological features, while reintroduction of dietary gluten caused rapid relapse. Gluten-sensitive rhesus macaques may be an attractive resource for investigating both the pathogenesis and the treatment of celiac disease.