Titre :

Biomarkers of haemodynamic severity of systemic sclerosis-associated pulmonary arterial hypertension by serum proteome analysis

Auteur(s) :

Sanges, Sebastien [Auteur]
Boston University [Boston] [BU]
Lille Inflammation Research International Center (LIRIC) - U995
Rice, Lisa [Auteur]
Boston University [Boston] [BU]
Tu, Ly [Auteur]
Hôpital Marie-Lannelongue
Université Paris-Saclay
Valenzi, Eleanor [Auteur]
University of Pittsburgh School of Medicine
Cracowski, Jean-Luc [Auteur]
Université Grenoble Alpes [2016-2019] [UGA [2016-2019]]
Montani, David [Auteur]
Hôpital Marie-Lannelongue
Université Paris-Saclay
Mantero, Julio C [Auteur]
Boston University [Boston] [BU]
Ternynck, Camille [Auteur]
CHU Lille - Direction de la recherche et de l’innovation
Marot, Guillemette [Auteur]
Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS]
MOdel for Data Analysis and Learning [MODAL]
METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694
Bujor, Andreea M [Auteur]
Tufts University School of Medicine [Boston]
Hachulla, Eric [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Launay, David [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Humbert, Marc [Auteur]

Hôpital Marie-Lannelongue
Université Paris-Saclay
Guignabert, Christophe [Auteur]
Hôpital Marie-Lannelongue
Université Paris-Saclay
Lafyatis, Robert [Auteur]
University of Pittsburgh School of Medicine

Titre de la revue :

Annals of the Rheumatic Diseases

Nom court de la revue :

Ann Rheum Dis

Numéro :

82

Pagination :

365-373

Éditeur :

BMJ

Date de publication :

2023-03

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Objectives: To mine the serum proteome of patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) and to detect biomarkers that may assist in earlier and more effective diagnosis and ...
Lire la suite >Objectives: To mine the serum proteome of patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) and to detect biomarkers that may assist in earlier and more effective diagnosis and treatment. Methods: Patients with limited cutaneous SSc, no extensive interstitial lung disease and no PAH-specific therapy were included. They were classified as cases if they had PAH confirmed by right heart catheterisation (RHC) and serum collected on the same day as RHC; and as controls if they had no clinical evidence of PAH. Results: Patients were mostly middle-aged females with anticentromere-associated SSc. Among 1129 proteins assessed by a high-throughput proteomic assay (SOMAscan), only 2 were differentially expressed and correlated significantly with pulmonary vascular resistance (PVR) in SSc-PAH patients (n=15): chemerin (ρ=0.62, p=0.01) and SET (ρ=0.62, p=0.01). To validate these results, serum levels of chemerin were measured by ELISA in an independent cohort. Chemerin levels were confirmed to be significantly higher (p=0.01) and correlate with PVR (ρ=0.42, p=0.04) in SSc-PAH patients (n=24). Chemerin mRNA expression was detected in fibroblasts, pulmonary artery smooth muscle cells (PA-SMCs)/pericytes and mesothelial cells in SSc-PAH lungs by single-cell RNA-sequencing. Confocal immunofluorescence revealed increased expression of a chemerin receptor, CMKLR1, on SSc-PAH PA-SMCs. SSc-PAH serum seemed to induce higher PA-SMC proliferation than serum from SSc patients without PAH. This difference appeared neutralised when adding the CMKLR1 inhibitor α-NETA.ConclusionChemerin seems an interesting surrogate biomarker for PVR in SSc-PAH. Increased chemerin serum levels and CMKLR1 expression by PA-SMCs may contribute to SSc-PAH pathogenesis by inducing PA-SMC proliferation.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
• METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694

Date de dépôt :

2023-07-21T11:32:42Z
2023-09-06T07:47:20Z
2023-09-06T07:58:36Z