Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism.

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.
© 2023. The Author(s).

Authors

María Jesús Iglesias, Laura Sanchez-Rivera, Manal Ibrahim-Kosta, Clément Naudin, Gaëlle Munsch, Louisa Goumidi, Maria Farm, Philip M Smith, Florian Thibord, Julia Barbara Kral-Pointner, Mun-Gwan Hong, Pierre Suchon, Marine Germain, Waltraud C Schrottmaier, P 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, Angel Martinez-Perez, Joseph Emmerich, Jean-François Deleuze, Jovan Antovic, Jose Manuel Soria Fernandez, Alice Assinger, Jochen M Schwenk, Juan Carlos Souto, Pierre-Emmanuel Morange, Lynn M Butler, David-Alexandre Trégouët, Jacob Odeberg

Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden. jacob1@kth.se, Division of Internal Medicine, University Hospital of North Norway (UNN), PB100, 9038, Tromsø, Norway. jacob1@kth.se, Translational Vascular Research, Department of Clinical Medicine, UiT The Arctic University of Norway, 9019, Tromsø, Norway. jacob1@kth.se, Department of Medicine Solna, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden. jacob1@kth.se, Coagulation Unit, Department of Haematology, Karolinska University Hospital, SE-171 76, Stockholm, Sweden. jacob1@kth.se.