Shenzhen Center for Chronic Disease Control and Prevention, Shenzhen, China.
Key Laboratory of RNA Biology and National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Medicine (Baltimore). 2022 Dec 30;101(52):e31652. doi: 10.1097/MD.0000000000031652.
Diabetes mellitus patients with pulmonary tuberculosis (DMTB) comorbidity has been recognized as a major obstacle towards achieving the World Health Organization goal of reducing the tuberculosis incidence rate by 90% in 2035. Host immune responses affected by diabetes can lead to increased susceptibility, severity and poor treatment outcomes in DMTB patients, and the underlying mechanisms have not yet been fully elucidated. This study aimed to identify key immunological and cellular components that contribute to increased morbidity and mortality in DMTB cases.
We performed RNA-Seq of total RNA isolated from peripheral blood mononuclear cells from 3 TB, 3 diabetes mellitus, and 3 DMTB patients and healthy controls, and analyzed differential expression, pathway enrichment and clustering of differentially-expressed genes (DEGs) to identify biological pathways altered specifically in DMTB patients.
Bioinformatic analysis of DEGs suggested that enhanced inflammatory responses, small GTPases, the protein kinase C signaling pathway, hemostasis and the cell cycle pathway are likely implicated in the pathogenesis of the DMTB comorbidity.
The DMTB comorbidity is associated with an altered transcriptome and changes in various biological pathways. Our study provides new insights on the pathological mechanism that may aid the development of host-directed therapies for this increasingly prevalent disease in high TB burden countries.
糖尿病合并肺结核（DMTB）已被认为是实现世界卫生组织 2035 年将结核病发病率降低 90%这一目标的主要障碍。糖尿病影响宿主免疫反应，可导致 DMTB 患者易感性增加、病情加重和治疗效果不佳，但其潜在机制尚未完全阐明。本研究旨在确定导致 DMTB 患者发病率和死亡率增加的关键免疫和细胞成分。
我们对 3 例结核病患者、3 例糖尿病患者和 3 例 DMTB 患者及健康对照者外周血单个核细胞总 RNA 进行 RNA-Seq 分析，并对差异表达基因（DEGs）进行差异表达、通路富集和聚类分析，以确定 DMTB 患者中特异性改变的生物学通路。
DEGs 的生物信息学分析表明，炎症反应增强、小 GTPases、蛋白激酶 C 信号通路、止血和细胞周期通路可能与 DMTB 合并症的发病机制有关。
DMTB 合并症与转录组改变和各种生物学通路变化有关。本研究为该疾病在高结核病负担国家日益流行的发病机制提供了新的见解，并可能有助于开发针对宿主的治疗方法。
