| Title: |
Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism. |
| Authors: |
Iglesias, MJ; Sanchez-Rivera, L; Ibrahim-Kosta, M; Naudin, C; Munsch, G; Goumidi, L; Farm, M; Smith, PM; Thibord, F; Kral-Pointner, JB; Hong, M-G; Suchon, P; Germain, M; Schrottmaier, W; Dusart, P; Boland, A; Kotol, D; Edfors, F; Koprulu, M; Pietzner, M; Langenberg, C; Damrauer, SM; Johnson, AD; Klarin, DM; Smith, NL; Smadja, DM; Holmström, M; Magnusson, M; Silveira, A; Uhlén, M; Renné, T; Martinez-Perez, A; Emmerich, J; Deleuze, J-F; Antovic, J; Soria Fernandez, JM; Assinger, A; Schwenk, JM; Souto Andres, JC; Morange, P-E; Butler, LM; Trégouët, D-A; Odeberg, J |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2023 |
| Collection: |
Queen Mary University of London: Queen Mary Research Online (QMRO) |
| Subject Terms: |
Humans; Biomarkers; Complement Activation; Complement Factor H; Complement System Proteins; Factor V; Venous Thromboembolism |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
3280 - ? |
| Language: |
English |
| Relation: |
Nat Commun; https://qmro.qmul.ac.uk/xmlui/handle/123456789/103597 |
| DOI: |
10.1038/s41467-023-38383-y |
| Availability: |
https://qmro.qmul.ac.uk/xmlui/handle/123456789/103597; https://doi.org/10.1038/s41467-023-38383-y |
| Rights: |
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. ; © The Author(s) 2023, corrected publication 2023 |
| Accession Number: |
edsbas.22832A9B |
| Database: |
BASE |