Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
University of Maryland, School of Medicine, Baltimore, MD, USA; Laboratory of Immune System Biology (LISB), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
Tuberculosis (Edinb). 2021 Jan;126:102036. doi: 10.1016/j.tube.2020.102036. Epub 2020 Dec 3.
To elucidate disease-specific host protein profile in vitreous fluid of patients with intraocular inflammation due to tubercular uveitis (TBU).
Vitreous samples from 13 patients with TBU (group A), 7 with non-TBU (group B) and 9 with no uveitis (group C) were analysed by shotgun proteomics using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS). Differentially expressed proteins (DEPs) were subjected to pathway analysis using WEB-based Gene SeT Analysis Toolkit software.
Compared to control groups (B + C combined), group A (TBU) displayed 32 (11 upregulated, 21 downregulated) DEPs, which revealed an upregulation of coagulation cascades, complement and classic pathways, and downregulation of metabolism of carbohydrates, gluconeogenesis, glucose metabolism and glycolysis/gluconeogenesis pathways. When compared to group B (non-TBU) alone, TBU displayed 58 DEPs (21 upregulated, 37 downregulated), with an upregulation of apoptosis, KRAS signaling, diabetes pathways, classic pathways, and downregulation of MTORC1 signaling, glycolysis/gluconeogenesis, and glucose metabolism.
This differential protein profile provides novel insights into the molecular mechanisms of TBU and a baseline to explore vitreous biomarkers to differentiate TBU from non-TBU, warranting future studies to identify and validate them as a diagnostic tool in TBU. The enriched pathways generate interesting hypotheses and drive further research.
阐明结核性葡萄膜炎(TBU)患者眼内炎症玻璃体液中特定于疾病的宿主蛋白谱。
使用液相色谱串联质谱(LC-MS/MS)通过 shotgun 蛋白质组学分析来自 13 例 TBU 患者(A 组)、7 例非 TBU 患者(B 组)和 9 例无葡萄膜炎患者(C 组)的玻璃体样本。使用基于网络的基因集分析工具包软件对差异表达蛋白(DEPs)进行途径分析。
与对照组(B+C 联合)相比,A 组(TBU)显示出 32 个(11 个上调,21 个下调)DEPs,表明凝血级联、补体和经典途径上调,碳水化合物代谢、糖异生、葡萄糖代谢和糖酵解/糖异生途径下调。与单独的 B 组(非 TBU)相比,TBU 显示出 58 个 DEPs(21 个上调,37 个下调),凋亡、KRAS 信号、糖尿病途径、经典途径上调,MTORC1 信号、糖酵解/糖异生、葡萄糖代谢下调。
这种差异蛋白谱为 TBU 的分子机制提供了新的见解,并为探索玻璃体生物标志物以区分 TBU 与非 TBU 提供了基线,值得进一步研究以鉴定和验证它们作为 TBU 的诊断工具。富集途径产生了有趣的假设并推动了进一步的研究。