The Gut Microbiome and HLA B27-associated Acute Anterior Uveitis

项目摘要 葡萄膜炎是后天致盲的主要原因之一。葡萄膜炎可根据解剖学进行细分 葡萄膜受影响的部分；85%的葡萄膜炎主要发生在前部。由于人类白细胞抗原B27与 在50%发生急性前葡萄膜炎的患者中，HLAB27相关的急性前葡萄膜炎很容易 葡萄膜炎最常见的表型。尽管人类白细胞抗原B7在S的发病机制中起到了显著作用 葡萄膜炎，解释这种影响的机制尚不清楚。使用老鼠模型，我们最近报告了 人类白细胞抗原B27塑造了微生物群，即共同栖息在人体内的微生物细胞。此外，我们注意到， 在大鼠模型中，特定的肠道细菌，包括关节假丝酵母菌，被IgA包被。此外, 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 人类白细胞抗原B27塑造人体微生物群并包被免疫球蛋白对患者的观察 与对照组相比，细菌在B27+受试者中更普遍。我们假设微生物群是 与B27相关的急性前葡萄膜炎有因果关系。我们进一步假设肠道细菌是 转移到葡萄膜等发炎部位。我们提出3个目标来检验这些假说。这些 研究代表了一种理解HLAB27相关疾病发病机制的创新方法，这是一个目标 尽管该协会很强大，但43年来一直难以捉摸。

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.