INFLAMMATORY BOWEL DISEASE CENTER: CLINICAL DATA REPOSITORY - TISSUE PROCUREMENT

炎症性肠病中心：临床数据存储库 - 组织采购

• 批准号: 7952200
• 负责人: Stephan R. Targan
• 金额: $ 15.17万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7952200
• 关键词: Animal Model; Animals; Antibiotic Therapy; Antibodies; Antineutrophil Cytoplasmic Antibodies; Bacterial Antigens; Biochemical Markers; Blood; Candidate Disease Gene; Cells; Characteristics; Chronic; Clinical; Clinical Data; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Crohn' s disease; Data; Databases; Development; Diagnostic; Disease; Enrollment; Evaluation; Funding; Gastrointestinal tract structure; Gender; Genes; Grant; Hospitals; Human; Immunologics; Immunology; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Infusion procedures; Institution; Intestinal Mucosa; Intestines; Label; Laboratories; Learning; Location; Maintenance; Molecular Abnormality; Names; New York; Participant; Patients; Persons; Population; Pouchitis; Procedures; Proteins; Protocols documentation; Research; Research Design; Research Personnel; Resources; Role; Saccharomyces cerevisiae; Sampling; Scanning; Serum; Source; Specimen; Stratification; Stream; Time; Tissue Procurements; Tissues; Ulcerative Colitis; United States National Institutes of Health; Work; commensal microbes; gastrointestinal; genetic association; human tissue; improved; interest; response; success; therapeutic target

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. Ulcerative colitis and Crohn's disease are chronic and debiliting inflammatory conditions of the intestinal tract, collectively refered to as inflammatory bowel disease (IBD). Much progress has been made in identifying the genes associated with these inflammatory disorders. Gene scanning and candidate gene approaches have revealed several disease-associated locations on relevant genes. One important implication of gene scanning studies is that at least three loci confirmed by independent groups, and an additional three others are suggested in some manifestations of IBD. Some of these genes are associated with Crohn's disease and or ulcerative colitis individually, and others are associated with both. Marker antibodies (proteins in the blood) and/or disease expression further refines the associations. Multiple studies in the human, as well as the animal studies summarized above, have demonstrated differing genetic associations with clinical characteristics as well as marker antibody expression. While headway has been made in localizing some of the genes important in IBD, much more work is needed to find which genes are involved, especially since evidence suggests that several genes are likely to act in concert in the development of these conditions. Since the discovery of perinculear antineutrophil cytoplasmic antibodies (pANCA) ten years ago, much has been learned about the presence of marker antibodies in the serum of patients with IBD. In addition to pANCA, interest has focused on another protein in the blood called Saccharomyces cerevisiae (ASCA), which have been shown to differentiate between ulcerative colitis and Crohn's disease. Our group has not only contributed to progress on these antibodies, but has further identified two new proteins (HupB and I2) which identify strongly disease-associated antibodies in Crohn's disease. These marker antibodies are important for their diagnostic utility and stratification of patients into distinct clinical types. These antibodies are associated not only with the different locations of disease, but also with aggressiveness of disease course as well as with responses to treatment by specific manipulation of gastrointestinal (GI)immunology. Although many inflammatory proteins are elevated in the GI tract of patients with IBD, their precise role in disease disease development has never been determined. In animal models, the success of treatment by manipulation GI immunology has led to trials of anti-TNF-a for the treatment of Crohn's disease. Results of these trials showed for the first time that certain immunologic cell in the GI tract could alter disease course in the majority of patients with Crohn's disease. Sixty-five percent of patients responded dramatically to a single infusion of anti-TNF-a. A proportion of Crohn's disease patients can be treated by manipulation of the bacterial flora by either antibiotic therapy or a diversion of the fecal stream, which suggests diverse responses to bacterial antigens among the Crohn's disease population. In ulcerative colitis, patients with high levels of pANCA are three times more likely to develop chronic pouchitis than patients without high levels of pANCA. These findings, taken together, highlight the potential importance of bacterial interactions in the induction or maintenance of inflammation. Overall, the diversity of clinical expression seen in IBD is very likely dependent upon a combination of genetic abnormalities and the presence of certain commensal bacteria. In summary, this umbrella procedure will provide human tissue and associated clinical data to facilitate and expedite numerous ongoing projects aimed at identifying the causes of IBD and to identify potential therapeutic targets. The Cedars-Sinai IBD Center conducts laboratory and clinical research designed to understand the causes and improve treatments for inflammatory bowel diseases (IBD); Crohn's disease and ulcerative colitis. Numerous studies, some sponsored by the NIH or other private entities, and some unfunded at present rely on the acquisition and evaluation of tissues (blood and/or intestinal mucosa) in association with correlated clinical data. The purpose of this protocol is to establish an umbrella procedure for enrolling participants and the subsequent use and/or storage of such samples and data resulting from these studies. Dr. Abreu, one of the original study investigators has relocated to Mt. Sinai Hospital in New York. She wil be given access to unidentified specimens for ongoing analysis. As always, our tissue specimens are labeled with only the year they were obtained and the sequential number as they were acquired (e.g. 05-023). After Dr. Abreu analyzes her specimens she may request from us information pertaining to their disease (CD or UC patient), treatment, gender and biochemical marker status. At no time will she receive any identifying information (patient name, MRN, etc.). Please be assured that the only persons who have access to PHI are Dr. Targan and the study coordinators.

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 溃疡性结肠炎和克罗恩病是肠道的慢性和使人衰弱的炎性病症，统称为炎症性肠病（IBD）。 在确定与这些炎症性疾病相关的基因方面已经取得了很大进展。基因扫描和候选基因方法已经揭示了相关基因上的几个疾病相关位置。基因扫描研究的一个重要意义是，至少有三个基因座被独立的研究小组证实，另外三个基因座被认为是IBD的某些表现。这些基因中的一些与克罗恩病和/或溃疡性结肠炎单独相关，而另一些则与两者都相关。标记抗体（血液中的蛋白质）和/或疾病表达进一步细化了这种关联。在人体中的多项研究以及上文总结的动物研究已经证明了与临床特征以及标志物抗体表达的不同遗传关联。虽然在定位IBD中的一些重要基因方面取得了进展，但需要做更多的工作来找到哪些基因参与其中，特别是因为有证据表明，几个基因可能在这些疾病的发展中共同发挥作用。 自从十年前发现核周抗神经细胞胞质抗体（pANCA）以来，人们对IBD患者血清中标记抗体的存在有了很大的了解。除了pANCA，人们的兴趣集中在血液中另一种称为酿酒酵母（ASCA）的蛋白质上，该蛋白质已被证明可以区分溃疡性结肠炎和克罗恩病。我们的研究小组不仅对这些抗体的研究进展做出了贡献，而且还进一步鉴定了两种新的蛋白质（HupB和I2），它们可以识别克罗恩病中与疾病相关的抗体。这些标记抗体对于它们的诊断效用和将患者分层为不同的临床类型是重要的。这些抗体不仅与疾病的不同部位相关，而且与疾病过程的侵袭性以及对通过胃肠道（GI）免疫学的特异性操作进行的治疗的反应相关。 虽然许多炎症蛋白在IBD患者的胃肠道中升高，但它们在疾病发展中的确切作用从未被确定。在动物模型中，通过操作GI免疫学的治疗的成功已经导致了用于治疗克罗恩病的抗TNF-α的试验。这些试验的结果首次表明，胃肠道中的某些免疫细胞可以改变大多数克罗恩病患者的病程。65%的患者对单次输注抗TNF-α有显著反应。一部分克罗恩病患者可以通过抗生素治疗或粪便流转移来操纵细菌植物群来治疗，这表明克罗恩病人群中对细菌抗原的反应不同。在溃疡性结肠炎中，pANCA水平高的患者发生慢性结肠袋炎的可能性是pANCA水平不高的患者的三倍。这些研究结果共同强调了细菌相互作用在诱导或维持炎症中的潜在重要性。总体而言，IBD中观察到的临床表达的多样性很可能取决于遗传异常和某些肠道细菌的存在。 总之，该伞形程序将提供人体组织和相关临床数据，以促进和加快旨在确定IBD病因和确定潜在治疗靶点的许多正在进行的项目。 Cedars-Sinai IBD中心进行实验室和临床研究，旨在了解炎症性肠病（IBD）的原因并改善治疗;克罗恩病和溃疡性结肠炎。许多研究，一些由NIH或其他私人实体赞助，一些目前没有资金支持，依赖于与相关临床数据相关的组织（血液和/或肠粘膜）的获取和评估。本方案的目的是为入组受试者以及随后使用和/或储存这些研究所得样本和数据建立一个总括程序。 博士Abreu，最初的研究人员之一，已经搬迁到山。纽约的西奈医院。她将被允许接触身份不明的样本进行持续的分析。与往常一样，我们的组织标本仅标记其获得的年份和获得时的序列号（例如05-023）。Abreu博士分析她的标本后，她可能会要求我们提供有关其疾病（CD或UC患者）、治疗、性别和生化标志物状态的信息。她在任何时候都不会收到任何识别信息（患者姓名、MRN等）。请放心，只有Targan博士和研究协调员可以访问PHI。