Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism.
Maria Jesus IglesiasLaura Sanchez-RiveraManal Ibrahim-KostaClément NaudinGaëlle MunschLouisa GoumidiMaria FarmPhilip M SmithFlorian ThibordJulia Barbara Kral-PointnerMun-Gwan HongPierre SuchonMarine GermainWaltraud Cornelia SchrottmaierPhilip J DusartAnne BolandDavid KotolFredrik EdforsMine KopruluMaik PietznerClaudia LangenbergScott M DamrauerAndrew Danner JohnsonDerek M KlarinNicholas L SmithDavid M SmadjaMargareta HolmströmMaria MagnussonAngela SilveiraMathias UhlenThomas RennéAngel Martinez-PerezJoseph EmmerichJean François DeleuzeJovan AntovicJose Manuel Soria FernandezAlice AssingerJochen M SchwenkJuan Carlos Carlos SoutoPierre-Emmanuel MorangeLynn Marie ButlerDavid Alexandre TrégouëtJacob OdebergPublished in: Nature communications (2023)
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.