Comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration

医学 葡萄膜炎 强直性脊柱炎 巩膜炎 生物标志物 发病机制 蛋白质组学 生物标志物发现 疾病 细胞外小泡 生物信息学 免疫学 病理 生物 生物化学 基因 细胞生物学
作者
Lingzi Wu,Lei Zhou,Jinying An,Xianfeng Shao,Hui Zhang,Handong Wang,Guixia Zhao,Shuang Chen,Xuexue Cui,Xinyi Zhang,Fuhua Yang,Xiaorong Li,Xiaomin Zhang
出处
期刊:Journal of Translational Medicine [BioMed Central]
卷期号:21 (1) 被引量:7
标识
DOI:10.1186/s12967-023-04228-x
摘要

Uveitis and posterior scleritis are sight-threatening diseases with undefined pathogenesis and accurate diagnosis remains challenging.Two plasma-derived extracellular vesicle (EV) subpopulations, small and large EVs, obtained from patients with ankylosing spondylitis-related uveitis, Behcet's disease uveitis, Vogt-Koyanagi-Harada syndrome, and posterior scleritis were subjected to proteomics analysis alongside plasma using SWATH-MS. A comprehensive bioinformatics analysis was performed on the proteomic profiles of sEVs, lEVs, and plasma. Candidate biomarkers were validated in a new cohort using ELISA. Pearson correlation analysis was performed to analyze the relationship between clinical parameters and proteomic data. Connectivity map database was used to predict therapeutic agents.In total, 3,668 proteins were identified and over 3000 proteins were quantified from 278 samples. When comparing diseased group to healthy control, the proteomic profiles of the two EV subgroups were more correlated with disease than plasma. Comprehensive bioinformatics analysis highlighted potential pathogenic mechanisms for these diseases. Potential biomarker panels for four diseases were identified and validated. We found a negative correlation between plasma endothelin-converting enzyme 1 level and mean retinal thickness. Potential therapeutic drugs were proposed, and their targets were identified.This study provides a proteomic landscape of plasma and EVs involved in ankylosing spondylitis-related uveitis, Behcet's disease uveitis, Vogt-Koyanagi-Harada syndrome, and posterior scleritis, offers insights into disease pathogenesis, identifies valuable biomarker candidates, and proposes promising therapeutic agents.
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