ArticleNature communications2023
Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism.
Erratum issuedOpen access · goldAbstract read
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Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
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19citing papers in PubMed
9.9field-weighted citation impact, top 2% of its field
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Biomarkers, mechanisms, and precision care in thrombosis.Journal of thrombosis and thrombolysis · 2026Article
- Association of FHR5 With Disease Severity in ANCA-Associated Vasculitis.Kidney international reports · 2026Article
- Proteomic Biomarkers in VTE: From Discovery to Clinical Translation.Journal of clinical medicine · 2026Review
- Identification of novel blood-borne soluble binding partners of factor H-related proteins.Scientific reports · 2026Article
- Candidate biomarkers to identify mesothelioma patients at risk of developing venous thromboembolism post-surgery.Scientific reports · 2026Article
- Proteomic Insights into Venous Thromboembolism.Medical sciences (Basel, Switzerland) · 2026Review
- Machine learning integration of bulk and single-cell RNA-Seq data reveals COPS2 as a central immune regulator in deep vein thrombosis.American journal of translational research · 2026Article
- Complement C3 in panvascular disease: a central integrator of immune signaling and vascular remodeling.Clinical science (London, England : 1979) · 2025Review
- Linear and non-linear proteome-wide association studies provide novel insight into venous thromboembolism.Nature communications · 2025Article
- Exploration of the plasma proteomic profile of patients at risk of thromboembolic events.Research and practice in thrombosis and haemostasis · 2025Article
- Complement activation assessed by C3bc and C5b-9 terminal complex as diagnostic biomarkers for deep vein thrombosis.PloS one · 2025Article
- Neonates exposed to HIV but uninfected exhibit an altered gut microbiota and inflammation associated with impaired breast milk antibody function.Microbiome · 2024Article
- The Circulating Proteome─Technological Developments, Current Challenges, and Future Trends.Journal of proteome research · 2024Article
- Proteomic profiling for biomarker discovery in heparin-induced thrombocytopenia.Blood advances · 2024Article
- The complement factor H-related protein-5 (CFHR5) exacerbates pathological bone formation in ankylosing spondylitis.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Identifying novel biomarkers using proteomics to predict cancer-associated thrombosis.Bleeding, thrombosis and vascular biology · 2024Article
- Identification of exosome protein panels as predictive biomarkers for non-small cell lung cancer.Biological procedures online · 2023Article
- Platelet factors are induced by longevity factor klotho and enhance cognition in young and aging mice.Nature aging · 2023Article
- Complement Overactivation as a Causal Driver of Sepsis-Associated Coagulopathy: A Mendelian Randomization Study from the UK Biobank.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
Corrections and comments
- Erratum issued
Authors and funding
43 authors at 15 institutions in 9 countries.
Maria Jesus Iglesias *Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden.
Laura Sanchez-Rivera *Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden.
Manal Ibrahim-KostaAix-Marseille Univ, INSERM, INRAE, C2VN, Laboratory of Haematology, CRB Assistance Publique-Hôpitaux de Marseille, HemoVasc (CRB AP-HM HemoVasc), Marseille, France.
Clément NaudinScience for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-6777-9587
Gaëlle MunschUniversity of Bordeaux, INSERM, Bordeaux Population Health Research Center, UMR 1219, ELEANOR, Bordeaux, France.ORCID http://orcid.org/0000-0003-1564-9825
Louisa GoumidiAix-Marseille Univ, INSERM, INRAE, C2VN, Laboratory of Haematology, CRB Assistance Publique-Hôpitaux de Marseille, HemoVasc (CRB AP-HM HemoVasc), Marseille, France.ORCID http://orcid.org/0000-0003-4164-8471
Maria FarmDepartment of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
Philip M SmithDepartment of Medicine Solna, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
Florian ThibordPopulation Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA, USA.
Julia Barbara Kral-PointnerCenter for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.
Mun-Gwan HongScience for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-8603-8293
Pierre SuchonAix-Marseille Univ, INSERM, INRAE, C2VN, Laboratory of Haematology, CRB Assistance Publique-Hôpitaux de Marseille, HemoVasc (CRB AP-HM HemoVasc), Marseille, France.
Marine GermainUniversity of Bordeaux, INSERM, Bordeaux Population Health Research Center, UMR 1219, ELEANOR, Bordeaux, France.
Waltraud SchrottmaierCenter for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0003-0550-4120
Philip DusartScience for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-2747-3214
Anne BolandUniversité Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH), 91057, Evry, France.
David KotolScience for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-5388-3826
Fredrik EdforsScience for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-0017-7987
Mine KopruluMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, CB2 0QQ, UK.ORCID http://orcid.org/0000-0001-6870-4539
Maik PietznerMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, CB2 0QQ, UK.ORCID http://orcid.org/0000-0003-3437-9963
Claudia LangenbergMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, CB2 0QQ, UK.ORCID http://orcid.org/0000-0002-5017-7344
Scott M DamrauerCorporal Michael Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8009-1632
Andrew D JohnsonPopulation Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA, USA.ORCID http://orcid.org/0000-0001-6369-5178
Derek M KlarinVA Palo Alto Healthcare System, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0002-4636-5780
Nicholas L SmithDepartment of Epidemiology, University of Washington, Seattle, WA, USA.
David M SmadjaHematology Department and Biosurgical Research Lab (Carpentier Foundation), European Georges Pompidou Hospital, Assistance Publique Hôpitaux de Paris, 20 rue Leblanc, Paris, 75015, France.
Margareta HolmströmCoagulation Unit, Department of Haematology, Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
Maria MagnussonDepartment of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
Angela SilveiraDepartment of Medicine Solna, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-2063-4935
Mathias UhlénScience for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-4858-8056
Thomas RennéInstitute for Clinical Chemistry and Laboratory Medicine, University Medical Centre Hamburg-Eppendorf, D-20246, Hamburg, Germany.
Angel Martinez-PerezGenomics of Complex Diseases Group, Research Institute Hospital de la Santa Creu i Sant Pau. IIB Sant Pau, Barcelona, Spain.ORCID http://orcid.org/0000-0002-5934-1454
Joseph EmmerichDepartment of vascular medicine, Paris Saint-Joseph Hospital Group, INSERM 1153-CRESS, University of Paris Cité, 185 rue Raymond Losserand, Paris, 75674, France.
Jean-Francois DeleuzeUniversité Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH), 91057, Evry, France.ORCID http://orcid.org/0000-0002-5358-4463
Jovan AntovicDepartment of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
Jose Manuel Soria FernandezGenomics of Complex Diseases Group, Research Institute Hospital de la Santa Creu i Sant Pau. IIB Sant Pau, Barcelona, Spain.
Alice AssingerCenter for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0002-5670-5910
Jochen M SchwenkScience for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-8141-8449
Joan Carles Souto AndresUnitat d'Hemostàsia i Trombosi. Hospital de la Santa Creu i Sant Pau and IIB-Sant Pau, Barcelona, Spain.ORCID http://orcid.org/0000-0003-2092-5142
Pierre-Emmanuel MorangeAix-Marseille Univ, INSERM, INRAE, C2VN, Laboratory of Haematology, CRB Assistance Publique-Hôpitaux de Marseille, HemoVasc (CRB AP-HM HemoVasc), Marseille, France.ORCID http://orcid.org/0000-0002-9065-722X
Lynn Marie ButlerScience for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-2352-8217
David-Alexandre TrégouëtUniversity of Bordeaux, INSERM, Bordeaux Population Health Research Center, UMR 1219, ELEANOR, Bordeaux, France. david-alexandre.tregouet@u-bordeaux.fr.ORCID http://orcid.org/0000-0001-9084-7800
Jacob OdebergScience for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, SE-171 21, Stockholm, Sweden. jacob1@kth.se.ORCID http://orcid.org/0000-0003-0996-1644
Science for Life Laboratory · SEKarolinska University Hospital · SEInserm · FRHospital de Sant Pau · ESMedical University of Vienna · ATUniversité de Bordeaux · FRCommissariat à l'Énergie Atomique et aux Énergies Alternatives · FRNational Heart Lung and Blood Institute · USQueen Mary University of London · GBUniversity Hospital of North Norway · NOKaiser Permanente Washington Health Research Institute · USPalo Alto University · USPhiladelphia VA Medical Center · USRoyal College of Surgeons in Ireland · IEUniversity of Cambridge · GB
Funding
Clonal hematopoiesis and risk of peripheral artery diseaseIK2BX005759 · VA · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · PI KLARIN, DEREK · 2022 to 2023
–Precision Cardio-Metabolic Phenotyping for Genetic Discovery and Risk PredictionIK2CX001780 · VA · PHILADELPHIA VA MEDICAL CENTER · PI DAMRAUER, SCOTT MICHAEL · 2018 to 2023
–Austrian Science Fund FWF P 34783BLRD VA IK2 BX005759Cancer Research UK C864/A14136CSRD VA IK2 CX001780Medical Research Council MC_PC_13048Medical Research Council MC_PC_21036Medical Research Council MC_UU_00006/1Medical Research Council MC-UU_12015/1Medical Research Council MC_UU_12015/1Medical Research Council MR/N003284/1
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.
Indexed as
Venous ThromboembolismBiomarkersComplement ActivationComplement Factor HComplement System ProteinsFactor VHumansBiomarkersCFHR5 protein, humanComplement Factor HComplement System ProteinsFactor V
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