Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism.
Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism.
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DOI：
10.1038/s41467-023-38383-y
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发表时间：
2023-06-07
影响因子：
16.6
通讯作者：
Odeberg J
中科院分区：
文献类型：
--
作者：
Iglesias MJ;Sanchez-Rivera L;Ibrahim-Kosta M;Naudin C;Munsch G;Goumidi L;Farm M;Smith PM;Thibord F;Kral-Pointner JB;Hong MG;Suchon P;Germain M;Schrottmaier W;Dusart P;Boland A;Kotol D;Edfors F;Koprulu M;Pietzner M;Langenberg C;Damrauer SM;Johnson AD;Klarin DM;Smith NL;Smadja DM;Holmström M;Magnusson M;Silveira A;Uhlén M;Renné T;Martinez-Perez A;Emmerich J;Deleuze JF;Antovic J;Soria Fernandez JM;Assinger A;Schwenk JM;Souto Andres JC;Morange PE;Butler LM;Trégouët DA;Odeberg J
静脉血栓栓塞（VTE）是一种常见的多病因疾病，具有潜在的严重短期和长期并发症。在临床实践中，需要用于VTE诊断和风险预测的改进的基于血浆生物标志物的工具。在这里，我们显示，使用蛋白质组学分析筛选疑似急性静脉血栓栓塞患者的血浆，以及几项静脉血栓栓塞的病例对照研究，补体因子H相关5蛋白（CFHR 5），补体激活旁路途径的调节剂，是一种静脉血栓栓塞相关的血浆生物标志物。在血浆中，较高的CFHR 5水平与凝血酶生成潜力增加和重组CFHR 5增强体外血小板活化相关。对约52，000名参与者进行的GWAS分析确定了与CFHR 5血浆水平相关的六个位点，但孟德尔随机化并未证明CFHR 5与VTE之间的因果关系。我们的研究结果表明，CFHR 5在调节静脉血栓栓塞症中补体激活的替代途径方面发挥着重要作用，并且CFHR 5代表了一种潜在的诊断和/或风险预测血浆生物标志物。需要改进基于生物标记物的静脉血栓栓塞（VTE）诊断和风险预测工具。在本文中，作者表明补体因子H相关5蛋白（补体激活旁路途径的调节剂）是5个独立队列中的VTE相关血浆生物标志物。
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. Improved biomarker-based tools for diagnosis and risk prediction of venous thromboembolism (VTE) are needed. Here, the authors show that Complement Factor H Related 5 protein, a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker in 5 independent cohorts.
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
20.3
作者：
Bruzelius, Maria;Iglesias, Maria Jesus;Odeberg, Jacob
通讯作者：
Odeberg, Jacob
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
4
作者：
Blostein, Mark D.;Rajotte, Isabelle;Kahn, Susan R.
通讯作者：
Kahn, Susan R.