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

• Published in: Nature communications Vol. 14; no. 1; pp. 3280 - 23
• Main Authors: Iglesias, Maria Jesus, Sanchez-Rivera, Laura, Ibrahim-Kosta, Manal, Naudin, Clément, Munsch, Gaëlle, Goumidi, Louisa, Farm, Maria, Smith, Philip M., Thibord, Florian, Kral-Pointner, Julia Barbara, Hong, Mun-Gwan, Suchon, Pierre, Germain, Marine, Schrottmaier, Waltraud, Dusart, Philip, Boland, Anne, Kotol, David, Edfors, Fredrik, Koprulu, Mine, Pietzner, Maik, Langenberg, Claudia, Damrauer, Scott M., Johnson, Andrew D., Klarin, Derek M., Smith, Nicholas L., Smadja, David M., Holmström, Margareta, Magnusson, Maria, Silveira, Angela, Uhlén, Mathias, Renné, Thomas, Martinez-Perez, Angel, Emmerich, Joseph, Deleuze, Jean-Francois, Antovic, Jovan, Soria Fernandez, Jose Manuel, Assinger, Alice, Schwenk, Jochen M., Souto Andres, Joan Carles, Morange, Pierre-Emmanuel, Butler, Lynn Marie, Trégouët, David-Alexandre, Odeberg, Jacob
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.06.2023; Nature Publishing Group; Springer Nature; Nature Portfolio
• Subjects: 45/43; 692/308/53/2421; 692/499; 692/53/2423; 692/699/75/593/1839; 82/1; 82/47; 82/58; 82/80; Alternative pathway; Biochemistry, Molecular Biology; Biomarkers; Complement; Complement Activation; Complement factor H; Complement Factor H - genetics; Complement System Proteins - metabolism; Diagnosis; Factor V; Genetics; Genomics; Human genetics; Humanities and Social Sciences; Humans; Life Sciences; multidisciplinary; Plasma; Plasma levels; Predictions; Proteins; Proteomics; Risk; Science; Science (multidisciplinary); Thrombin; Thromboembolism; Venous Thromboembolism - genetics
• ISSN: 2041-1723; 2041-1723
• 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. 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.