作者
María Jesús Iglesias,Laura Sánchez-Rivera,Manal Ibrahim‐Kosta,Clément Naudin,Gaëlle Munsch,Louisa Goumidi,Maria Farm,Philip Smith,Florian Thibord,Julia B. Kral-Pointner,Mun‐Gwan Hong,Pierre Suchon,Marine Germain,Waltraud C. Schrottmaier,Philip Dusart,Anne Boland,David Kotol,Fredrik Edfors,Mine Koprulu,Maik Pietzner,Claudia Langenberg,Scott M. Damrauer,Andrew D. Johnson,Derek Klarin,Nicholas L. Smith,David M. Smadja,Margareta Holmström,Maria Magnusson,Angela Silveira,Mathias Uhlén,Thomas Renné,Ángel Martínez-Pérez,Joseph Emmerich,Jean-François Deleuze,Jovan P. Antović,Jose Manuel Soria Fernandez,Alice Assinger,Jochen M. Schwenk,Joan Carles Souto,Pierre‐Emmanuel Morange,Lynn M. Butler,David‐Alexandre Trégouët,Jacob Odeberg
摘要
Abstract 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.