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

基本信息

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
项目类别：
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

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

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项目摘要

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失明的主要原因之一。可以根据解剖学细分葡萄膜炎受影响的葡萄病的一部分； 85％的葡萄膜炎主要是前部。由于HLA B27与患有急性前葡萄膜炎的患者中有50％，HLA B27相关的急性前葡萄膜炎很容易是葡萄膜炎的最常见表型。尽管HLA B7在促进发病机理方面发挥着出色的作用葡萄膜炎，解释这种作用的机制尚不清楚。使用大鼠模型，我们最近报告了 HLA B27塑造了与人体共持的微生物细胞的微生物组。此外，我们注意到在大鼠模型中，特定的肠道细菌在包括念珠菌的促腹膜膜中涂有IgA。此外，大鼠模型中的细菌从肠道转换为关节。重要的是，我们推断了这些通过证明HLA B27塑造了患者的观察细菌在B27+受试者相对于对照组中更为普遍。我们假设微生物组是与B27相关的急性前葡萄膜炎的因果关系。我们进一步假设肠道细菌是易位到炎症部位，例如卵子。我们提出了3个旨在检验这些假设的目标。这些研究代表了一种创新的方法来了解HLA B27相关疾病的发病机理，这是一个目标目的地已有43年的目的地，这是该协会的实力。