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：
10228030
负责人：
JAMES T ROSENBAUM
金额：
$ 36.33万
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/10228030
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

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.

项目概要葡萄膜炎是获得性失明的主要原因之一。葡萄膜炎可根据解剖学进行细分。受影响的葡萄膜部分；85% 的葡萄膜炎主要是前葡萄膜炎，因为 HLA B27 与此相关。 50%的患者出现急性前葡萄膜炎，HLA B27相关的急性前葡萄膜炎很容易尽管 HLA B7 在葡萄膜炎的发病机制中发挥着显着的作用。葡萄膜炎，解释这种效应的机制尚不清楚，我们最近使用大鼠模型报告了这一点。 HLA B27 塑造微生物组，即与人体共存的微生物细胞。在大鼠模型中，包括 Candidatus arthromatus 在内的特定肠道细菌被 IgA 包被。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。通过对患者进行的观察，显示 HLA B27 塑造人体微生物组，并且 IgA 包被相对于对照组，细菌在 B27+ 受试者中更为普遍。与 B27 相关的急性前葡萄膜炎有因果关系。我们进一步解决了肠道细菌与 B27 相关的急性前葡萄膜炎的因果关系。我们提出 3 个目的来检验这些假设。研究代表了一种了解 HLA B27 相关疾病发病机制的创新方法，这是一个目标尽管该协会实力雄厚，但 43 年来一直难以实现。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Novel Inter-omic Analysis Reveals Relationships Between Diverse Gut Microbiota and Host Immune Dysregulation in HLA-B27-Induced Experimental Spondyloarthritis.

新颖的组间分析揭示了 HLA-B27 诱导的实验性脊柱关节炎中不同肠道微生物群与宿主免疫失调之间的关系。

DOI：
发表时间：
2019
期刊：
影响因子：
0
作者：
Gill, Tejpal;Brooks, Stephen R;Rosenbaum, James T;Asquith, Mark;Colbert, Robert A
通讯作者：
Colbert, Robert A

HLA-A alleles including HLA-A29 affect the composition of the gut microbiome: a potential clue to the pathogenesis of birdshot retinochoroidopathy.

包括 HLA-A29 在内的 HLA-A 等位基因影响肠道微生物组的组成：鸟弹性视网膜脉络膜病变发病机制的潜在线索。

DOI：
发表时间：
2020
期刊：
影响因子：
4.6
作者：
Sternes, Peter R;Martin, Tammy M;Paley, Michael;Diamond, Sarah;Asquith, Mark J;Brown, Matthew A;Rosenbaum, James T
通讯作者：
Rosenbaum, James T

Just another crappy commentary: the future of fecal microbiota transplantation.

只是另一个蹩脚的评论：粪便微生物移植的未来。