PDGFB, a new candidate plasma biomarker for venous thromboembolism: results from the VEREMA affinity proteomics study
Por:
Bruzelius, M, Iglesias, MJ, Hong, MG, Sanchez-Rivera, L, Gyorgy, B, Souto, JC, Franberg, M, Fredolini, C, Strawbridge, RJ, Holmstrom, M, Hamsten, A, Uhlen, M, Silveira, A, Soria, JM, Smadja, DM, Butler, LM, Schwenk, JM, Morange, PE, Tregouet, DA, Odeberg, J
Publicada:
8 dic 2016
Resumen:
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 beta (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 (rho similar to 0.30) with each other, they were independently associated with VTE risk in a joint model in FARIVE (VWF P < .001; PDGFB P = .002). PDGF. 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.
Filiaciones:
Bruzelius, M:
Karolinska Univ Hosp, Coagulat Unit, Hematol Ctr, Stockholm, Sweden
Karolinska Inst, Dept Med Solna, Stockholm, Sweden
Iglesias, MJ:
KTH Royal Inst Technol, Sch Biotechnol, Dept Prote, Sci Life Lab, Stockholm, Sweden
Hong, MG:
KTH Royal Inst Technol, Sch Biotechnol, Dept Prote, Sci Life Lab, Stockholm, Sweden
Sanchez-Rivera, L:
KTH Royal Inst Technol, Sch Biotechnol, Dept Prote, Sci Life Lab, Stockholm, Sweden
Gyorgy, B:
Inst Cardiometab, Paris, France
Nutr Inst Cardiometab & Nutr, Paris, France
Souto, JC:
IIB St Pau, Unitat Hemostasia & Trombosi, Barcelona, Spain
Franberg, M:
Karolinska Inst, Dept Med Solna, Stockholm, Sweden
Stockholm Univ, Dept Numer Anal & Comp Sci, Stockholm, Sweden
Fredolini, C:
KTH Royal Inst Technol, Sch Biotechnol, Dept Prote, Sci Life Lab, Stockholm, Sweden
Strawbridge, RJ:
Karolinska Inst, Dept Med Solna, Stockholm, Sweden
Holmstrom, M:
Karolinska Univ Hosp, Coagulat Unit, Hematol Ctr, Stockholm, Sweden
Hamsten, A:
Karolinska Inst, Dept Med Solna, Stockholm, Sweden
Uhlen, M:
KTH Royal Inst Technol, Sch Biotechnol, Dept Prote, Sci Life Lab, Stockholm, Sweden
Silveira, A:
Karolinska Inst, Dept Med Solna, Stockholm, Sweden
Soria, JM:
IIB St Pau, Unitat Genom Malalties Complexes, Barcelona, Spain
Smadja, DM:
Univ Paris 05, Sorbonne Paris Cite, Paris, France
Fac Pharm Paris, INSERM, UMR S1140, Paris, France
Hop Europeen Georges Pompidou, AP HP, Serv Hematol Biol, Paris, France
Butler, LM:
Karolinska Inst, Dept Mol Med & Surg, Clin Chem, Stockholm, Sweden
Univ Med Ctr Hamburg Eppendorf, Inst Clin Chem & Lab Med, Hamburg, Germany
Schwenk, JM:
KTH Royal Inst Technol, Sch Biotechnol, Dept Prote, Sci Life Lab, Stockholm, Sweden
Morange, PE:
Aix Marseille Univ, UMR S 1062, Nutr Obes & Risk Thrombosis, Marseille, France
La Timone Hosp, Hematol Lab, Marseille, France
Tregouet, DA:
Inst Cardiometab, Paris, France
Nutr Inst Cardiometab & Nutr, Paris, France
Sorbonne Univ, Pierre & Marie Curie Univ, Univ Paris 06, INSERM,UMR S 1166,Team Genom & Pathophysiol Cardi, Paris, France
Odeberg, J:
Karolinska Univ Hosp, Coagulat Unit, Hematol Ctr, Stockholm, Sweden
Karolinska Inst, Dept Med Solna, Stockholm, Sweden
KTH Royal Inst Technol, Sch Biotechnol, Dept Prote, Sci Life Lab, Stockholm, Sweden
Bronze
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