Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism
Por:
Iglesias M.J., Sanchez-Rivera L., Ibrahim-Kosta M., Naudin C., Munsch G., Goumidi L., Farm M., Smith P.M., Thibord F., Kral-Pointner J.B., Hong M.-G., Suchon P., Germain M., Schottmaier W., Dusart P., Boland A., Kotol D., Edfors F., Koprulu M., Pietzner M., Langenberg C., Damrauer S.M., Johnson A.D., Klarin D.M., Smith N.L., Smadja D.M., Holmström M., Magnusson M., Silveira A., Uhlén M., Renné T., Martinez-Perez A., Emmerich J., Deleuze J.-F., Antovic J., Soria Fernandez J.M., Assinger A., Schwenk J.M., Souto Andres J.C., Morange P.-E., Butler L.M., Trégouët D.-A., Odeberg J.
Publicada:
1 ene 2023
Ahead of Print:
7 jun 2023
Resumen:
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.
Filiaciones:
Iglesias M.J.:
Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden
Division of Internal Medicine, University Hospital of North Norway (UNN), PB100, Tromsø, 9038, Norway
Translational Vascular Research, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, 9019, Norway
Sanchez-Rivera L.:
Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden
Ibrahim-Kosta M.:
Aix-Marseille Univ, INSERM, INRAE, C2VN, Laboratory of Haematology, CRB Assistance Publique—Hôpitaux de Marseille, HemoVasc (CRB AP-HM HemoVasc), Marseille, France
Naudin C.:
Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden
Translational Vascular Research, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, 9019, Norway
Munsch G.:
University of Bordeaux, INSERM, Bordeaux Population Health Research Center, ELEANOR, Bordeaux, UMR 1219, France
Goumidi L.:
Aix-Marseille Univ, INSERM, INRAE, C2VN, Laboratory of Haematology, CRB Assistance Publique—Hôpitaux de Marseille, HemoVasc (CRB AP-HM HemoVasc), Marseille, France
Farm M.:
Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden
Smith P.M.:
Department of Medicine Solna, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden
Theme of Emergency and Reparative Medicine, Karolinska University Hospital, Stockholm, Sweden
Thibord F.:
Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA, United States
The Framingham Heart Study, Boston University, Framingham, MA, United States
Kral-Pointner J.B.:
Center for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria
Hong M.-G.:
Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden
Suchon P.:
Aix-Marseille Univ, INSERM, INRAE, C2VN, Laboratory of Haematology, CRB Assistance Publique—Hôpitaux de Marseille, HemoVasc (CRB AP-HM HemoVasc), Marseille, France
Germain M.:
University of Bordeaux, INSERM, Bordeaux Population Health Research Center, ELEANOR, Bordeaux, UMR 1219, France
Laboratory of Excellence GENMED (Medical Genomics), Bordeaux, France
Schottmaier W.:
Center for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria
Dusart P.:
Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden
Translational Vascular Research, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, 9019, Norway
Boland A.:
Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH), Evry, 91057, France
Laboratory of Excellence GENMED (Medical Genomics), Evry, France
Kotol D.:
Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden
Edfors F.:
Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden
Koprulu M.:
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, CB2 0QQ, United Kingdom
Pietzner M.:
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, CB2 0QQ, United Kingdom
Computational Medicine, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, 10117, Germany
Precision Healthcare University Research Institute, Queen Mary University of London, London, United Kingdom
Langenberg C.:
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, CB2 0QQ, United Kingdom
Computational Medicine, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, 10117, Germany
Precision Healthcare University Research Institute, Queen Mary University of London, London, United Kingdom
Damrauer S.M.:
Corporal Michael Crescenz VA Medical Center, Philadelphia, PA, United States
Department of Surgery and Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
Johnson A.D.:
Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA, United States
The Framingham Heart Study, Boston University, Framingham, MA, United States
Klarin D.M.:
VA Palo Alto Healthcare System, Palo Alto, CA, United States
Department of Vascular Surgery, Stanford University School of Medicine, Palo Alto, CA, United States
Smith N.L.:
Department of Epidemiology, University of Washington, Seattle, WA, United States
Kaiser Permanente Washington Health Research Institute, Seattle, WA, United States
Seattle Epidemiologic Research and Information Center, Department of Veterans Affairs Office of Research and Development, Seattle, WA, United States
Smadja D.M.:
Hematology Department and Biosurgical Research Lab (Carpentier Foundation), European Georges Pompidou Hospital, Assistance Publique Hôpitaux de Paris, 20 rue Leblanc, Paris, 75015, France
Innovative Therapies in Haemostasis, INSERM, Université de Paris, 4 avenue de l’Observatoire, Paris, 75270, France
Holmström M.:
Coagulation Unit, Department of Haematology, Karolinska University Hospital, SE-171 76, Stockholm, Sweden
Magnusson M.:
Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
Coagulation Unit, Department of Haematology, Karolinska University Hospital, SE-171 76, Stockholm, Sweden
Department of Clinical Science, Intervention and Technology, Karolinska Institute, 171 77, Stockholm, Sweden
Silveira A.:
Department of Medicine Solna, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden
Uhlén M.:
Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden
Renné T.:
Institute for Clinical Chemistry and Laboratory Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, D-20246, Germany
Center for Thrombosis and Hemostasis (CTH), Johannes Gutenberg University Medical Center, D-, Mainz, 55131, Germany
Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin 2, D02 YN77, Ireland
Martinez-Perez A.:
Genomics of Complex Diseases Group, Research Institute Hospital de la Santa Creu i Sant Pau. IIB Sant Pau, Barcelona, Spain
Emmerich J.:
Department of vascular medicine, Paris Saint-Joseph Hospital Group, INSERM 1153-CRESS, University of Paris Cité, 185 rue Raymond Losserand, Paris, 75674, France
Deleuze J.-F.:
Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH), Evry, 91057, France
Laboratory of Excellence GENMED (Medical Genomics), Evry, France
Centre D’Etude du Polymorphisme Humain, Fondation Jean Dausset, Paris, France
Antovic J.:
Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden
Soria Fernandez J.M.:
Genomics of Complex Diseases Group, Research Institute Hospital de la Santa Creu i Sant Pau. IIB Sant Pau, Barcelona, Spain
Assinger A.:
Center for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria
Schwenk J.M.:
Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden
Souto Andres J.C.:
Unitat d’Hemostàsia i Trombosi. Hospital de la Santa Creu i Sant Pau and IIB-Sant Pau, Barcelona, Spain
Morange P.-E.:
Aix-Marseille Univ, INSERM, INRAE, C2VN, Laboratory of Haematology, CRB Assistance Publique—Hôpitaux de Marseille, HemoVasc (CRB AP-HM HemoVasc), Marseille, France
Butler L.M.:
Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden
Translational Vascular Research, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, 9019, Norway
Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden
Trégouët D.-A.:
University of Bordeaux, INSERM, Bordeaux Population Health Research Center, ELEANOR, Bordeaux, UMR 1219, France
Laboratory of Excellence GENMED (Medical Genomics), Bordeaux, France
Odeberg J.:
Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden
Division of Internal Medicine, University Hospital of North Norway (UNN), PB100, Tromsø, 9038, Norway
Translational Vascular Research, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, 9019, Norway
Department of Medicine Solna, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden
Coagulation Unit, Department of Haematology, Karolinska University Hospital, SE-171 76, Stockholm, Sweden
Green Submitted, gold, Green Published, All Open Access, Gold, Green
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