The Gut Microbiome and HLA B27-associated Acute Anterior Uveitis

肠道微生物组和 HLA B27 相关的急性前葡萄膜炎

• 批准号: 9764405
• 负责人: Mark Asquith
• 金额: $ 37.82万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9764405
• 关键词: 16S ribosomal RNA sequencing; Acquired Blindness; Acute; Adult; Affect; Anatomy; Ankylosing spondylitis; Anterior; Anterior uveitis; Antigens; Bacteria; Biopsy; Blindness; Blood; Cell surface; Cells; Clinical; Colitis; Colonoscopy; Communities; Complement; Complex; Degenerative polyarthritis; Deposition; Disease; Ecosystem; Elements; FOXP3 gene; Feces; Frequencies; Gene Expression; Goals; HLA-B27 Antigen; Habits; Household; Human; Human Microbiome; Human body; Immune; Immunoglobulin A; Immunologics; Individual; Inflammation; Inflammation Mediators; Inflammatory; Interleukin-17; Intestines; Joints; LCN2 gene; Length; Leukocyte L1 Antigen Complex; Leukocytes; Lymphoid Cell; Major Histocompatibility Complex; Mediating; Microbe; Modeling; Mucosal Immune System; Organism; Pathogenesis; Pathogenicity; Pathology; Patients; Phenotype; Play; Population; Psoriatic Arthritis; Rattus; Recording of previous events; Regulatory T-Lymphocyte; Reiter Disease; Reporting; Rheumatoid Arthritis; Risk; Role; Sampling; Shapes; Site; Spondylarthritis; Synovial Membrane; Synovitis; Testing; Transgenic Organisms; Uvea; Uveitis; Viral; arthropathies; base; fecal microbiome; gut bacteria; gut microbes; gut microbiome; human disease; innovation; microbial; microbiome; microbiota; mouse model; next generation sequencing; novel; prevent; rRNA Genes; transcriptome sequencing

Project Summary Uveitis is one of the leading causes of acquired blindness. Uveitis can be subdivided based on the anatomic portion of the uvea that is affected; 85% of uveitis is predominantly anterior. Since HLA B27 is associated with 50% of the patients who develop acute anterior uveitis, HLA B27 related acute anterior uveitis is easily the most common phenotype of uveitis. Despite HLA B7’s remarkable role in contributing to the pathogenesis of uveitis, the mechanism that explains this effect is unknown. Using a rat model, we have recently reported that HLA B27 shapes the microbiome, the microbial cells that co-habit the human body. Furthermore, we note that specific gut bacteria including Candidatus arthromatus are coated with IgA in the rat model. In addition, bacteria in the rat model are translocated from the gut to the joint. Importantly we have extrapolated these observations to patients by showing that HLA B27 shapes the microbiome in people and that IgA coated bacteria are more prevalent in B27+ subjects relative to controls. We hypothesize that the microbiome is causally related to B27-related acute anterior uveitis. We further hypothesize that intestinal bacteria are translocated to sites of inflammation such as the uvea. We propose 3 aims to test these hypotheses. These studies represent an innovative approach to understand the pathogenesis of HLA B27-related disease, a goal which has been elusive for 43 years despite the strength of the association.

项目摘要 葡萄膜炎是获得性失明的主要原因之一。葡萄膜炎可以根据解剖结构进行细分 受影响的葡萄膜部分; 85%的葡萄膜炎主要是前部。由于HLA B27与 在50%的急性前葡萄膜炎患者中，HLA-B27相关的急性前葡萄膜炎容易发生。 最常见的葡萄膜炎表型。尽管HLA-B7在导致糖尿病的发病机制中发挥着重要作用， 葡萄膜炎，解释这种效果的机制是未知的。使用大鼠模型，我们最近报道， HLA B27塑造了微生物组，即共同居住在人体内的微生物细胞。此外，我们注意到， 在大鼠模型中用伊加包被特定的肠道细菌，包括关节炎链球菌。此外，本发明还提供了一种方法， 大鼠模型中的细菌从肠道转移到关节。重要的是，我们已经推断出这些 通过对患者的观察，显示HLA B27塑造了人体内的微生物组， 细菌在B27+受试者中相对于对照更普遍。我们假设微生物组 与B27相关急性前葡萄膜炎有因果关系。我们进一步假设肠道细菌是 转移到炎症部位如葡萄膜。我们提出3个目的来检验这些假设。这些 研究代表了一种创新的方法来了解HLA B27相关疾病的发病机制， 尽管该协会实力雄厚，但43年来一直难以捉摸。