Cytokines as prognostic biomarkers in pulmonary arterial hypertension
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
INTRODUCTION: Risk stratification and assessment of disease progression in patients with pulmonary arterial hypertension (PAH) are challenged by the lack of accurate disease-specific and prognostic biomarkers. To date, B-type natriuretic peptide (BNP) and/or its N-terminal fragment (NT-proBNP) are the only marker for right ventricular dysfunction used in clinical practice, in association with echocardiographic and invasive hemodymamic variables to predict outcome in patients with PAH. METHODS: This study was designed to identify an easily measurable biomarker panel in the serum of 80 well-phenotyped PAH patients with idiopathic, heritable, or drug-induced PAH at baseline and first follow-up. The prognostic value of identified cytokines of interest was secondly analysed in an external validation cohort of 125 PAH patients. RESULTS: Among the 20 biomarkers studied with the multiplex EllaTM platform, we identified a 3-biomarker panel composed of ß-NGF, CXCL9 and TRAIL that were independently associated with prognosis both at the time of PAH diagnosis and at the first follow-up after initiation of PAH therapy. β-NGF and CXCL9 were predictors of death or transplantation, whereas high levels of TRAIL were associated with a better prognosis. Furthermore, prognostic value of the three cytokines was more powerful for predicting survival than usual non-invasive variables (functional class, 6-minute walking distance and BNP/NT-proBNP). The results were validated in a fully independent external validation cohort. CONCLUSION: The monitoring of ß-NGF, CXCL9 and TRAIL levels in serum should be considered in the management and treatment of patients with PAH to objectively guide therapeutic options.
Date Issued
2022-03-23
Date Acceptance
2022-11-12
Citation
European Respiratory Journal, 2022, 61 (3)
ISSN
0903-1936
Publisher
European Respiratory Society
Journal / Book Title
European Respiratory Journal
Volume
61
Issue
3
Copyright Statement
“This is an author-submitted, peer-reviewed version of a manuscript that has been accepted for publication in the European Respiratory Journal, prior to copy-editing, formatting and typesetting. This version of the manuscript may not be duplicated or reproduced without prior permission from the European Respiratory Society. The publisher is not responsible or liable for any errors or omissions in this version of the manuscript or in any version derived from it by any other parties. The final, copy-edited, published article, which is the version of record, is available without a subscription 18 months after the date of issue publication.”
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/36549710
PII: 13993003.01232-2022
Publication Status
Published
Coverage Spatial
England
Article Number
2201232
Date Publish Online
2022-12-22