Plasma markers in pulmonary hypertension subgroups correlate with patient survival.

Autor: Koudstaal T; Department of Pulmonary Medicine, Erasmus MC, University Medical Center, Doctor Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands., van Uden D; Department of Pulmonary Medicine, Erasmus MC, University Medical Center, Doctor Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands., van Hulst JAC; Department of Pulmonary Medicine, Erasmus MC, University Medical Center, Doctor Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands., Heukels P; Department of Pulmonary Medicine, Erasmus MC, University Medical Center, Doctor Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands., Bergen IM; Department of Pulmonary Medicine, Erasmus MC, University Medical Center, Doctor Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands., Geenen LW; Department of Cardiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands., Baggen VJM; Department of Cardiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands., van den Bosch AE; Department of Cardiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands., van den Toorn LM; Department of Pulmonary Medicine, Erasmus MC, University Medical Center, Doctor Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands., Chandoesing PP; Department of Pulmonary Medicine, Erasmus MC, University Medical Center, Doctor Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands., Kool M; Department of Pulmonary Medicine, Erasmus MC, University Medical Center, Doctor Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands., Boersma E; Department of Cardiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.; Department of Clinical Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands., Hendriks RW; Department of Pulmonary Medicine, Erasmus MC, University Medical Center, Doctor Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands., Boomars KA; Department of Pulmonary Medicine, Erasmus MC, University Medical Center, Doctor Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands. k.boomars@erasmusmc.nl.
Jazyk: angličtina
Zdroj: Respiratory research [Respir Res] 2021 May 04; Vol. 22 (1), pp. 137. Date of Electronic Publication: 2021 May 04.
DOI: 10.1186/s12931-021-01716-w
Abstrakt: Background: Recent studies have provided evidence for an important contribution of the immune system in the pathophysiology of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). In this report, we investigated whether the inflammatory profile of pulmonary hypertension patients changes over time and correlates with patient WHO subgroups or survival.
Methods: 50 PAH patients (16 idiopathic (I)PAH, 24 Connective Tissue Disease (CTD)-PAH and 10 Congenital Heart Disease (CHD)-PAH), 37 CTEPH patients and 18 healthy controls (HCs) were included in the study. Plasma inflammatory markers at baseline and after 1-year follow-up were measured using ELISAs. Subsequently, correlations with hemodynamic parameters and survival were explored and data sets were subjected to unbiased multivariate analyses.
Results: At diagnosis, we found that plasma levels of interleukin-6 (IL-6) and the chemokines (C-X3-C) motif legend CXCL9 and CXCL13 in CTD-PAH patients were significantly increased, compared with HCs. In idiopathic PAH patients the levels of tumor growth factor-β (TGFβ), IL-10 and CXCL9 were elevated, compared with HCs. The increased CXCL9 and IL-8 concentrations in CETPH patients correlated significantly with decreased survival, suggesting that CXCL9 and IL-8 may be prognostic markers. After one year of treatment, IL-10, CXCL13 and TGFβ levels changed significantly in the PAH subgroups and CTEPH patients. Unbiased multivariate analysis revealed clustering of PH patients based on inflammatory mediators and clinical parameters, but did not separate the WHO subgroups. Importantly, these multivariate analyses separated patients with < 3 years and > 3 years survival, in particular when inflammatory mediators were combined with clinical parameters.
Discussion: Our study revealed elevated plasma levels of inflammatory mediators in different PAH subgroups and CTEPH at baseline and at 1-year follow-up, whereby CXCL9 and IL-8 may prove to be prognostic markers for CTEPH patients. While this study is exploratory and hypothesis generating, our data indicate an important role for IL-8 and CXCL9 in CHD and CTEPH patients considering the increased plasma levels and the observed correlation with survival.
Conclusion: In conclusion, our studies identified an inflammatory signature that clustered PH patients into WHO classification-independent subgroups that correlated with patient survival.
Databáze: MEDLINE
Externí odkaz: