Discovery of Potential Serum Protein Biomarkers in Ankylosing Spondylitis Using Tandem Mass Tag-Based Quantitative Proteomics

作者：Shijia Liu, Wei Ji, Jiawei Lu, Xiaojun Tang, Yunke Guo, Mingde Ji, Tian Xu, Wanjian Gu, Deshun Kong, Qiuxiang Shen, Dandan Wang, Xiangyu Lv, Jue Wang, Tianyao Zhu, Youjuan Zhu, Ping Liu, Jinfeng Su, Lu Wang, Yuhua Li, Pan Gao, Wei Liu, Lingyun Sun, Xiaojian Yin, Wei Zhou · 发表于：Journal of Proteome Research · 年份：2020 · DOI：10.1021/acs.jproteome.9b00676 · 被引用次数：24 · 研究领域：Spondyloarthritis Studies and Treatments、Rheumatoid Arthritis Research and Therapies、Inflammasome and immune disorders

Ankylosing spondylitis (AS) is a systemic, chronic, and inflammatory rheumatic disease that affects 0.2% of the population. Current diagnostic criteria for disease activity rely on subjective Bath Ankylosing Spondylitis Disease Activity Index scores. Here, we aimed to discover a panel of serum protein biomarkers. First, tandem mass tag (TMT)-based quantitative proteomics was applied to identify differential proteins between 15 pooled active AS and 60 pooled healthy subjects. Second, cohort 1 of 328 humans, including 138 active AS and 190 healthy subjects from two independent centers, was used for biomarker discovery and validation. Finally, biomarker panels were applied to differentiate among active AS, stable AS, and healthy subjects from cohort 2, which enrolled 28 patients with stable AS, 26 with active AS, and 28 healthy subjects. From the proteomics study, a total of 762 proteins were identified and 46 proteins were up-regulated and 59 proteins were down-regulated in active AS patients compared to those in healthy persons. Among them, C-reactive protein (CRP), complement factor H-related protein 3 (CFHR3), α-1-acid glycoprotein 2 (ORM2), serum amyloid A1 (SAA1), fibrinogen γ (FG-γ), and fibrinogen β (FG-β) were the most significantly up-regulated inflammation-related proteins and S100A8, fatty acid-binding protein 5 (FABP5), and thrombospondin 1 (THBS1) were the most significantly down-regulated inflammation-related proteins. From the cohort 1 study, the best panel for t...