title: PDGFB, a new candidate plasma biomarker for venous thromboembolism: results from the VEREMA affinity proteomics study.
abstract: There is a clear clinical need for high-specificity plasma biomarkers for predicting risk of venous thromboembolism (VTE), but thus far, such markers have remained elusive. Utilizing affinity reagents from the Human Protein Atlas project and multiplexed immuoassays, we extensively analyzed plasma samples from 2 individual studies to identify candidate protein markers associated with VTE risk. We screened plasma samples from 88 VTE cases and 85 matched controls, collected as part of the Swedish "Venous Thromboembolism Biomarker Study," using suspension bead arrays composed of 755 antibodies targeting 408 candidate proteins. We identified significant associations between VTE occurrence and plasma levels of human immunodeficiency virus type I enhancer binding protein 1 (HIVEP1), von Willebrand factor (VWF), glutathione peroxidase 3 (GPX3), and platelet-derived growth factor β (PDGFB). For replication, we profiled plasma samples of 580 cases and 589 controls from the French FARIVE study. These results confirmed the association of VWF and PDGFB with VTE after correction for multiple testing, whereas only weak trends were observed for HIVEP1 and GPX3. Although plasma levels of VWF and PDGFB correlated modestly (ρ ∼ 0.30) with each other, they were independently associated with VTE risk in a joint model in FARIVE (VWF P < .001; PDGFB P = .002). PDGFΒ was verified as the target of the capture antibody by immunocapture mass spectrometry and sandwich enzyme-linked immunosorbent assay. In conclusion, we demonstrate that high-throughput affinity plasma proteomic profiling is a valuable research strategy to identify potential candidate biomarkers for thrombosis-related disorders, and our study suggests a novel association of PDGFB plasma levels with VTE.
authors.affiliation: Coagulation Unit, Hematology Centre, Karolinska University Hospital, Stockholm, Sweden.|Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Bruzelius
authors.affiliation: Department of Proteomics, School of Biotechnology, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Maria Jesus
authors.identifier: 0000-0003-4122-1945
authors.initials: MJ
authors.lastname: Iglesias
authors.affiliation: Department of Proteomics, School of Biotechnology, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Mun-Gwan
authors.identifier: 0000-0001-8808-7128
authors.initials: MG
authors.lastname: Hong
authors.affiliation: Department of Proteomics, School of Biotechnology, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Laura
authors.initials: L
authors.lastname: Sanchez-Rivera
authors.affiliation: Institute of Cardiometabolism and Nutrition Institute for Cardiometabolism and Nutrition, Paris, France.
authors.forename: Beata
authors.initials: B
authors.lastname: Gyorgy
authors.affiliation: Unitat d'Hemostàsia i Trombosi, IIB-Sant Pau, Barcelona, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Souto
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.|Department of Numerical Analysis and Computer Science, Stockholm University, Stockholm, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Frånberg
authors.affiliation: Department of Proteomics, School of Biotechnology, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Claudia
authors.identifier: 0000-0002-7674-2014
authors.initials: C
authors.lastname: Fredolini
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rona J
authors.identifier: 0000-0001-8506-3585
authors.initials: RJ
authors.lastname: Strawbridge
authors.affiliation: Coagulation Unit, Hematology Centre, Karolinska University Hospital, Stockholm, Sweden.|Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Margareta
authors.initials: M
authors.lastname: Holmström
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anders
authors.identifier: 0000-0002-0618-0538
authors.initials: A
authors.lastname: Hamsten
authors.affiliation: Department of Proteomics, School of Biotechnology, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Angela
authors.identifier: 0000-0003-2063-4935
authors.initials: A
authors.lastname: Silveira
authors.affiliation: Unitat de Genòmica de Malalties Complexes, IIB-Sant Pau, Barcelona, Spain.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Soria
authors.affiliation: Sorbonne Paris Cité, Université Paris Descartes, Paris, France.|INSERM UMR-S1140, Faculté de Pharmacie de Paris, Paris, France.|l'Assistance Publique-Hôpitaux de Paris, Service d'Hématologie Biologique, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: David M
authors.identifier: 0000-0001-7731-9202
authors.initials: DM
authors.lastname: Smadja
authors.affiliation: Clinical Chemistry, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.|Institute for Clinical Chemistry and Laboratory Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Lynn M
authors.identifier: 0000-0002-2352-8217
authors.initials: LM
authors.lastname: Butler
authors.affiliation: Department of Proteomics, School of Biotechnology, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Jochen M
authors.identifier: 0000-0001-8141-8449
authors.initials: JM
authors.lastname: Schwenk
authors.affiliation: Aix-Marseille University, UMR_S 1062, Nutrition Obesity and Risk of Thrombosis, Marseille, France.|Laboratory of Hematology, La Timone Hospital, Marseille, France; and.
authors.forename: Pierre-Emmanuel
authors.identifier: 0000-0002-9065-722X
authors.initials: PE
authors.lastname: Morange
authors.affiliation: Institute of Cardiometabolism and Nutrition Institute for Cardiometabolism and Nutrition, Paris, France.|Sorbonne Universités, Pierre and Marie Curie University University of Paris 06, INSERM, UMR_S 1166, Team Genomics and Pathophysiology of Cardiovascular Diseases, Paris, France.
authors.forename: David-Alexandre
authors.initials: DA
authors.lastname: Trégouët
authors.affiliation: Coagulation Unit, Hematology Centre, Karolinska University Hospital, Stockholm, Sweden.|Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.|Department of Proteomics, School of Biotechnology, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Jacob
authors.identifier: 0000-0003-0996-1644
authors.initials: J
authors.lastname: Odeberg
mesh_terms: D015415:Biomarkers / Q000097:blood; D004268:DNA-Binding Proteins / Q000097:blood; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood; D006801:Humans; D008297:Male; D040901:Proteomics; D020574:Proto-Oncogene Proteins c-sis / Q000097:blood*; D012307:Risk Factors; D014157:Transcription Factors / Q000097:blood; D054556:Venous Thromboembolism / Q000097:blood*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; C063232:HIVEP1 protein, human; D020574:Proto-Oncogene Proteins c-sis; D014157:Transcription Factors; D014841:von Willebrand Factor; C486484:GPX3 protein, human; D005979:Glutathione Peroxidase