Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden.
Division of Internal Medicine, University Hospital of North Norway (UNN), PB100, 9038, Tromsø, Norway.
Nat Commun. 2023 Jun 7;14(1):3280. doi: 10.1038/s41467-023-38383-y.
Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement Factor H Related 5 protein (CFHR5), a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.
静脉血栓栓塞症（VTE）是一种常见的、多病因的疾病，具有潜在的严重短期和长期并发症。在临床实践中，需要改进基于血浆生物标志物的工具来进行 VTE 的诊断和风险预测。在这里，我们通过对疑似急性 VTE 患者的血浆进行蛋白质组学分析，并进行了几项 VTE 的病例对照研究，展示了补体因子 H 相关蛋白 5（CFHR5），一种补体激活替代途径的调节剂，是一种与 VTE 相关的血浆生物标志物。在血浆中，较高的 CFHR5 水平与增加的凝血酶生成潜力和重组 CFHR5 增强体外血小板激活有关。对~52000 名参与者的全基因组关联分析确定了与 CFHR5 血浆水平相关的六个位点，但孟德尔随机化分析并未表明 CFHR5 与 VTE 之间存在因果关系。我们的结果表明，补体激活替代途径的调节在 VTE 中起着重要作用，CFHR5 代表了一种潜在的诊断和/或风险预测性血浆生物标志物。
