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.

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。 溃疡性结肠炎和克罗恩病是一种慢性肠道炎症性疾病，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在相关基因上发现了几个与疾病相关的位置。基因扫描研究的一个重要意义是，在IBD的一些表现中，至少有三个座位得到了独立小组的确认，另外还有另外三个座位。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，另一些与两者都相关。标记抗体(血液中的蛋白质)和/或疾病的表达进一步细化了这种关联。在人类中的多项研究，以及上面总结的动物研究，都证明了不同的遗传与临床特征以及标记抗体的表达有关。虽然在定位IBD中的一些重要基因方面已经取得了进展，但还需要做更多的工作来找出涉及哪些基因，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协同作用。 自从10年前发现周围抗中性粒细胞胞浆抗体以来，人们对IBD患者血清中是否存在标志性抗体有了很大的了解。除了panca，人们的兴趣还集中在血液中另一种名为酿酒酵母(ASCA)的蛋白质上，这种蛋白质已被证明可以区分溃疡性结肠炎和克罗恩病。我们的团队不仅在这些抗体方面取得了进展，而且还进一步鉴定了两种新的蛋白质(HupB和I2)，这两种蛋白质在克罗恩病中识别了强烈的疾病相关抗体。这些标志物抗体对于它们的诊断作用和将患者分成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有关，而且与病程的侵袭性以及通过胃肠道(GI)免疫学的特定操作治疗的反应有关。 虽然许多炎性蛋白在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，通过操纵胃肠道免疫学治疗的成功导致了抗肿瘤坏死因子-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以改变大多数克罗恩病患者的病程。65%的患者对单次注射抗肿瘤坏死因子-a有显著反应。一部分克罗恩病患者可以通过抗生素治疗或改变粪便流向来操纵细菌菌群，这表明克罗恩病患者对细菌抗原的反应是不同的。在溃疡性结肠炎中，高水平的panca患者患慢性膀胱炎的可能性是没有高水平panca的患者的三倍。这些发现加在一起，突显了细菌相互作用在诱导或维持炎症方面的潜在重要性。总体而言，IBD临床表现的多样性很可能取决于遗传异常和某些共生细菌的存在。 总而言之，这一总括程序将提供人体组织和相关的临床数据，以促进和加快旨在确定IBD病因和确定潜在治疗靶点的众多正在进行的项目。 锡达斯-西奈IBD中心进行实验室和临床研究，旨在了解炎症性肠病(IBD)、克罗恩病和溃疡性结肠炎的病因并改进治疗方法。许多研究，有些是由NIH或其他私人实体赞助的，有些目前没有资金支持，依赖于组织(血液和/或肠粘膜)的获取和评估以及相关的临床数据。该议定书的目的是为登记参与者以及随后使用和/或储存这些研究产生的样本和数据建立一个总括程序。 最初的研究调查人员之一阿布瑞乌博士已经搬到了芒特山。纽约的西奈医院。她将被允许接触身份不明的样本进行正在进行的分析。像往常一样，我们的组织标本只标有获取的年份和获取的序列号(例如05-023)。在Abreu博士分析了她的标本后，她可能会要求我们提供关于他们的疾病(CD或UC患者)、治疗、性别和生化标记物状态的信息。她在任何时候都不会收到任何身份信息(患者姓名、MRN等)。请放心，只有Targan博士和研究协调员才能接触到PHI。