NONINFLAMMATORY GLUTEN PEPTIDE ANALOGUES AS BIOMARKERS FOR CELIAC SPRUE

非炎症性麸质肽类似物作为乳糜泻的生物标志物

• 批准号: 8172996
• 负责人: KAROL SESTAK
• 金额: $ 6.18万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172996
• 关键词: Animals; Biological Markers; Celiac Disease; Clinical Research; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Disease; Drug Metabolic Detoxication; Enterocytes; Funding; Glutamine; Gluten; Grant; Immune System Diseases; In Vitro; Inflammatory; Institution; Intestines; Patients; Peptide Hydrolases; Peptides; Permeability; Pharmaceutical Preparations; Research; Research Personnel; Resistance; Resources; Small Intestines; Source; Stomach; T-Lymphocyte; Transglutaminases; United States National Institutes of Health; gastrointestinal; peptide analog; tool

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. New tools are needed for managing celiac sprue, a lifelong immune disease of the small intestine. Ongoing drug trials are also prompting a search for non-invasive biomarkers of gluten-induced intestinal change. We have synthesized and characterized non-inflammatory gluten peptide analogues in which key Gln residues are replaced by Asn or His. Like their pro-inflammatory counterparts, these biomarkers are resistant to gastrointestinal proteases, susceptible to glutenases, and permeable across enterocyte barriers. Unlike gluten peptides, however, they are not appreciably recognized by transglutaminase, HLA-DQ2 or disease-specific T cells. In vitro and animal studies show that the biomarkers can detect intestinal permeability changes as well as glutenase-catalyzed gastric detoxification of gluten. Accordingly, controlled clinical studies are warranted to evaluate the use of these peptides as probes for abnormal intestinal permeability in celiac patients and for glutenase efficacy in clinical trials and practice.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 需要新的工具来治疗乳糜泻，这是一种终生的小肠免疫疾病。 正在进行的药物试验也促使人们寻找麸质引起的肠道变化的非侵入性生物标志物。 我们合成并表征了非炎性麸质肽类似物，其中关键的谷氨酰胺残基被 Asn 或 His 取代。 与促炎生物标志物一样，这些生物标志物对胃肠道蛋白酶具有抵抗力，对谷蛋白酶敏感，并且可渗透肠细胞屏障。 然而，与麸质肽不同的是，它们不能被转谷氨酰胺酶、HLA-DQ2 或疾病特异性 T 细胞明显识别。 体外和动物研究表明，生物标志物可以检测肠道通透性变化以及麸质酶催化的胃麸质解毒。 因此，有必要进行对照临床研究来评估这些肽作为乳糜泻患者肠道通透性异常的探针的用途以及临床试验和实践中谷蛋白酶的功效。