Bacterial Dysbiosis in IgG4-RD

IgG4-RD 中的细菌生态失调

• 批准号: 8732925
• 负责人: Ramnik J Xavier
• 金额: $ 10.85万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8732925
• 关键词: Affect; Aftercare; Autoimmune Diseases; Autoimmune Process; Autoimmunity; CD4 Positive T Lymphocytes; Cells; Characteristics; Cicatrix; Clinical; Communities; Crohn' s disease; DNA; Development; Disease; Generations; Genes; Genetic; Genotype; Helper-Inducer T-Lymphocyte; Human; IgG4; Immune; Individual; Inflammatory; Inflammatory Bowel Diseases; Interferon Type II; Intestines; Knowledge; Link; Longitudinal Studies; Microbe; Monitor; Oral; Oral cavity; Organ; Pathogenesis; Pathway interactions; Patients; Phenotype; Population; Process; RNA; Role; Salivary Gland Diseases; Salivary Glands; Shapes; Site; Subgroup; T-Lymphocyte; T-Lymphocyte Subsets; Therapeutic Intervention; Tissue Extracts; Tissue Sample; Tissues; Whole-Genome Shotgun Sequencing; base; cohort; cytokine; disorder subtype; experience; metabolomics; metagenome; microbial; microbial community; microbiome; mycobacterial; next generation sequencing; oral microbiome; pathogen; research study

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.

在这个项目中，我们试图了解口腔和肠道微生物菌群的改变如何有助于 IgG4相关疾病的发病机制。关于这种疾病和克隆优势的最新研究 表达干扰素 γ 的辅助 T 细胞表明与克罗恩病以及 分枝杆菌疾病、微生物在其中的作用毫无疑问。独特的存在 极化 T 细胞群还表明特定肠道微生物物种或 疾病过程中的社区。因此，有充分的理由来研究微生物组 IgG4 相关疾病。 这些研究包括三个方面。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。 我们还将研究口腔微生物菌群，将唾液腺和腭疾病患者与患有唾液腺和腭疾病的患者进行比较 那些不涉及这些器官的患者，也根据临床和临床情况对患者进行隔离 免疫学特征和遗传差异。 我们还将检查具有不同临床、免疫学和临床特征的受试者的肠道微生物菌群。 不同细菌群落成员的遗传上不同的疾病亚型，看看是否 社区成员资格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 lgG4-RD 受试者的定义亚组在以下方面是否存在差异： 宏基因组或宏转录组。