Nature Communications (Jun 2023)
Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism
- 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 Schrottmaier,
- 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
Affiliations
- Maria Jesus Iglesias
- Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology
- Laura Sanchez-Rivera
- Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology
- Manal Ibrahim-Kosta
- Aix-Marseille Univ, INSERM, INRAE, C2VN, Laboratory of Haematology, CRB Assistance Publique—Hôpitaux de Marseille
- Clément Naudin
- Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology
- Gaëlle Munsch
- University of Bordeaux, INSERM, Bordeaux Population Health Research Center
- Louisa Goumidi
- Aix-Marseille Univ, INSERM, INRAE, C2VN, Laboratory of Haematology, CRB Assistance Publique—Hôpitaux de Marseille
- Maria Farm
- Department of Molecular Medicine and Surgery, Karolinska Institute
- Philip M. Smith
- Department of Medicine Solna, Karolinska Institute and Karolinska University Hospital
- Florian Thibord
- Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute
- Julia Barbara Kral-Pointner
- Center for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna
- Mun-Gwan Hong
- Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology
- Pierre Suchon
- Aix-Marseille Univ, INSERM, INRAE, C2VN, Laboratory of Haematology, CRB Assistance Publique—Hôpitaux de Marseille
- Marine Germain
- University of Bordeaux, INSERM, Bordeaux Population Health Research Center
- Waltraud Schrottmaier
- Center for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna
- Philip Dusart
- Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology
- Anne Boland
- Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH)
- David Kotol
- Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology
- Fredrik Edfors
- Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology
- Mine Koprulu
- MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science
- Maik Pietzner
- MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science
- Claudia Langenberg
- MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science
- Scott M. Damrauer
- Corporal Michael Crescenz VA Medical Center
- Andrew D. Johnson
- Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute
- Derek M. Klarin
- VA Palo Alto Healthcare System
- Nicholas L. Smith
- Department of Epidemiology, University of Washington
- David M. Smadja
- Hematology Department and Biosurgical Research Lab (Carpentier Foundation), European Georges Pompidou Hospital, Assistance Publique Hôpitaux de Paris
- Margareta Holmström
- Coagulation Unit, Department of Haematology, Karolinska University Hospital
- Maria Magnusson
- Department of Molecular Medicine and Surgery, Karolinska Institute
- Angela Silveira
- Department of Medicine Solna, Karolinska Institute and Karolinska University Hospital
- Mathias Uhlén
- Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology
- Thomas Renné
- Institute for Clinical Chemistry and Laboratory Medicine, University Medical Centre Hamburg-Eppendorf
- Angel Martinez-Perez
- Genomics of Complex Diseases Group, Research Institute Hospital de la Santa Creu i Sant Pau. IIB Sant Pau
- Joseph Emmerich
- Department of vascular medicine, Paris Saint-Joseph Hospital Group, INSERM 1153-CRESS, University of Paris Cité
- Jean-Francois Deleuze
- Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH)
- Jovan Antovic
- Department of Molecular Medicine and Surgery, Karolinska Institute
- Jose Manuel Soria Fernandez
- Genomics of Complex Diseases Group, Research Institute Hospital de la Santa Creu i Sant Pau. IIB Sant Pau
- Alice Assinger
- Center for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna
- Jochen M. Schwenk
- Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology
- Joan Carles Souto Andres
- Unitat d’Hemostàsia i Trombosi. Hospital de la Santa Creu i Sant Pau and IIB-Sant Pau
- Pierre-Emmanuel Morange
- Aix-Marseille Univ, INSERM, INRAE, C2VN, Laboratory of Haematology, CRB Assistance Publique—Hôpitaux de Marseille
- Lynn Marie Butler
- Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology
- David-Alexandre Trégouët
- University of Bordeaux, INSERM, Bordeaux Population Health Research Center
- Jacob Odeberg
- Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology
- DOI
- https://doi.org/10.1038/s41467-023-38383-y
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 23
Abstract
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.
