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  • 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.

Nature communications (2023-06-08)
Maria Jesus 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 Schottmaier, Philip Dusart, Anne Boland, David Kotol, Fredrik Edfors, Mine Koprulu, Maik Pietzner, Claudia Langenberg, Scott M Damrauer, Andrew D Johnson, Derek M Klarin, Nicholas L Smith, David M Smadja, Margareta Holmström, Maria Magnusson, Angela Silveira, Mathias Uhlén, Thomas Renné, Angel Martinez-Perez, Joseph Emmerich, Jean-Francois Deleuze, Jovan Antovic, Jose Manuel Soria Fernandez, Alice Assinger, Jochen M Schwenk, Joan Carles Souto Andres, Pierre-Emmanuel Morange, Lynn Marie Butler, David-Alexandre Trégouët, Jacob Odeberg
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Plasma, from chicken
Sigma-Aldrich
Complement C3 from human serum, ≥3000 C3H50 units/mg (using C3 deficient serum)
Sigma-Aldrich
Anti-Complement C3a/C3a (desArg) Antibody, clone K13/16, clone K13/16, from mouse
Sigma-Aldrich
C-Reactive Protein