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: 7606129
• 负责人: Stephan R. Targan
• 金额: $ 5.69万
• 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: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606129
• 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; Condition; 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; Localized; Location; Maintenance; Molecular Abnormality; Names; New York; Numbers; Participant; Patients; Persons; Population; Pouchitis; Procedures; Proteins; Protocols documentation; Purpose; 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 溃疡性结肠炎和克罗恩病是慢性和衰弱的肠道炎症状况，统称称为炎症性肠病（IBD）。 在识别与这些炎症性疾病相关的基因方面取得了很多进展。基因扫描和候选基因方法揭示了相关基因的几个相关位置。基因扫描研究的一个重要含义是，至少三个由独立群体证实的基因座，在IBD的某些表现中提出了另外三个基因座。这些基因中的一些与克罗恩病和 /或单独的溃疡性结肠炎有关，而另一些则与两者相关。标记抗体（血液中的蛋白质）和/或疾病表达进一步完善了关联。人类的多项研究以及上述动物研究表明，与临床特征以及标记抗体表达的遗传关联不同。尽管在本地化一些重要的IBD基因方面取得了进展，但需要更多的工作才能找到涉及哪些基因，尤其是因为证据表明，有几个基因可能在这些条件的发展中起作用。 自从十年前发现周围抗营养性细胞质抗体（PANCA）以来，关于IBD患者的血清中标记抗体的存在已有很多了解。除panca外，兴趣还集中在称为酿酒酵母（ASCA）的血液中的另一种蛋白质上，这些蛋白已被证明可以区分溃疡性结肠炎和克罗恩病。我们的小组不仅有助于这些抗体的进展，而且还进一步鉴定了两种新蛋白质（HUPB和I2），它们在克罗恩病中鉴定了与疾病相关的抗体。这些标记抗体对于它们的诊断效用和将患者分为不同的临床类型很重要。这些抗体不仅与疾病的不同位置有关，还与疾病病程的侵略性以及通过特异性操纵胃肠道（GI）免疫学对治疗的反应有关。 尽管在IBD患者的胃肠道中，许多炎症蛋白升高，但从未确定它们在疾病发育中的精确作用。在动物模型中，通过操纵GI免疫学对治疗的成功导致了抗TNF-A治疗克罗恩病的试验。这些试验的结果首次表明，胃肠道中的某些免疫细胞可能会改变大多数克罗恩病患者的疾病病程。 65％的患者对抗TNF-A进行了单一的反应。克罗恩病患者的一部分可以通过通过抗生素疗法或粪便流的转移来治疗细菌菌群来治疗，这表明克罗恩病人群中对细菌抗原的反应多样化。在溃疡性结肠炎中，高水平的pance患者发展慢性囊炎的可能性是没有panca高水平的患者。这些发现共同强调了细菌相互作用在炎症诱导或维持中的潜在重要性。总体而言，在IBD中看到的临床表达的多样性很可能取决于遗传异常和某些共生细菌的存在的结合。 总而言之，该保护伞程序将提供人体组织和相关的临床数据，以促进和加快旨在识别IBD原因并确定潜在治疗靶点的许多正在进行的项目。 Cedars-Sinai IBD中心进行了实验室和临床研究，旨在了解炎症性肠病（IBD）的原因并改善治疗方法；克罗恩病和溃疡性结肠炎。许多研究，有些是由NIH或其他私人实体赞助的，而有些研究目前却依赖于对组织（血液和/或肠粘膜）的获取和评估以及相关的临床数据。该协议的目的是建立一个伞程序，以招募参与者，并随后使用和/或存储这些样品以及由这些研究产生的数据。 原始研究调查人员之一阿布鲁（Abreu）博士已搬到纽约西奈山医院。她将可以访问未知的标本进行持续分析。与往常一样，我们的组织标本仅在获得的一年和获得的顺序数字（例如05-023）上标记。 Abreu博士分析她的标本后，她可能会要求美国信息与其疾病有关（CD或UC患者），治疗，性别和生化标记状态。她绝对不会收到任何识别信息（患者姓名，MRN等）。请放心，唯一可以使用PHI的人是Targan博士和研究协调员。