Bacterial Dysbiosis in IgG4-RD

在这个项目中，我们试图了解口腔和肠道微生物植物群的改变如何有助于 lgG 4相关疾病的发病机制。近年来对该病害的研究及克隆优势度分析 表达干扰素γ的辅助性T细胞提示与克罗恩病以及 分枝杆菌疾病，其中微生物的作用是没有问题的疾病。一种独特的 极化的T细胞群也表明可能涉及特定的肠道微生物物种或 社区在疾病过程中。因此，有一个强有力的理由来研究微生物组 与IgG 4相关的疾病 这些研究有三个方面。一方面，我们将直接检查来自 使用下一代测序方法检测患病器官中微生物成分的存在。 我们还将观察唾液腺和腭部疾病患者的口腔微生物植物群， 那些不涉及这些器官的患者，并根据临床和 免疫学特征和遗传差异。 我们还将检查具有不同临床、免疫学和病理学特征的受试者的肠道微生物植物群。 基因上不同的疾病亚型，以确定不同的细菌群落成员， 社区成员身份会导致疾病或可能因疾病过程而改变。我们将 监测治疗后社区成员的变化，试图回答这个问题。 最后，我们将询问定义的lgG 4-RD受试者亚组在以下方面是否存在差异： 宏基因组或元转录组。

In this project we seek to understand how alterations in the oral and gut microbial flora might contribute to the pathogenesis of lgG4-related disease. Recent studies on this disease and the dominance of clonal interferon gamma expressing helper T cells suggests broad similarities to Crohn's disease as well as to mycobacterial diseases, disorders in which the role of microbes in not in question. The presence of a unique polarized T cell population also suggests the potential involvement of specific intestinal microbial species or communities in the disease process. There is a strong case to be made therefore to look at the microbiome in lgG4-related disease. There are three aspects to these studies. In one aspect we will directly examine tissue samples from diseased organs for the presence of microbial components using Next Generation Sequencing approaches. We will also look at the oral microbial flora comparing patients with salivary gland and palatal disease with those in which these organs are not involved and also segregate patients based on clinical and immunological characteristics and genetic differences. We will also examine the intestinal microbial flora in subjects with different clinical, immunological and genetically distinct disease subtypes for distinct bacterial community memberships to see whether community memberships contribute to disease or are potentially altered by the disease process. We will monitor changes in community memberships after treatment to attempt to answer this issue. Finally we will ask if defined subgroups of subjects with lgG4-RD have differences in terms of the metagenome or the metatranscriptome.