Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism
Standard
Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism. / Iglesias, Maria Jesus; Sanchez-Rivera, Laura; Ibrahim-Kosta, Manal; Naudin, Clément; Munsch, Gaëlle; Goumidi, Louisa; Farm, Maria; Smith, Philip M; Thibord, Florian; Kral-Pointner, Julia Barbara; Hong, Mun-Gwan; Suchon, Pierre; Germain, Marine; Schottmaier, Waltraud; Dusart, Philip; Boland, Anne; Kotol, David; Edfors, Fredrik; Koprulu, Mine; Pietzner, Maik; Langenberg, Claudia; Damrauer, Scott M; Johnson, Andrew D; Klarin, Derek M; Smith, Nicholas L; Smadja, David M; Holmström, Margareta; Magnusson, Maria; Silveira, Angela; Uhlén, Mathias; Renné, Thomas; Martinez-Perez, Angel; Emmerich, Joseph; Deleuze, Jean-Francois; Antovic, Jovan; Soria Fernandez, Jose Manuel; Assinger, Alice; Schwenk, Jochen M; Souto Andres, Joan Carles; Morange, Pierre-Emmanuel; Butler, Lynn Marie; Trégouët, David-Alexandre; Odeberg, Jacob.
in: NAT COMMUN, Jahrgang 14, Nr. 1, 07.06.2023, S. 3280.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism
AU - Iglesias, Maria Jesus
AU - Sanchez-Rivera, Laura
AU - Ibrahim-Kosta, Manal
AU - Naudin, Clément
AU - Munsch, Gaëlle
AU - Goumidi, Louisa
AU - Farm, Maria
AU - Smith, Philip M
AU - Thibord, Florian
AU - Kral-Pointner, Julia Barbara
AU - Hong, Mun-Gwan
AU - Suchon, Pierre
AU - Germain, Marine
AU - Schottmaier, Waltraud
AU - Dusart, Philip
AU - Boland, Anne
AU - Kotol, David
AU - Edfors, Fredrik
AU - Koprulu, Mine
AU - Pietzner, Maik
AU - Langenberg, Claudia
AU - Damrauer, Scott M
AU - Johnson, Andrew D
AU - Klarin, Derek M
AU - Smith, Nicholas L
AU - Smadja, David M
AU - Holmström, Margareta
AU - Magnusson, Maria
AU - Silveira, Angela
AU - Uhlén, Mathias
AU - Renné, Thomas
AU - Martinez-Perez, Angel
AU - Emmerich, Joseph
AU - Deleuze, Jean-Francois
AU - Antovic, Jovan
AU - Soria Fernandez, Jose Manuel
AU - Assinger, Alice
AU - Schwenk, Jochen M
AU - Souto Andres, Joan Carles
AU - Morange, Pierre-Emmanuel
AU - Butler, Lynn Marie
AU - Trégouët, David-Alexandre
AU - Odeberg, Jacob
N1 - © 2023. The Author(s).
PY - 2023/6/7
Y1 - 2023/6/7
N2 - 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.
AB - 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.
KW - Humans
KW - Biomarkers
KW - Complement Activation
KW - Complement Factor H/genetics
KW - Complement System Proteins/metabolism
KW - Factor V
KW - Venous Thromboembolism/genetics
U2 - 10.1038/s41467-023-38383-y
DO - 10.1038/s41467-023-38383-y
M3 - SCORING: Journal article
C2 - 37286573
VL - 14
SP - 3280
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
ER -