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Journal Articles Annals of the Rheumatic Diseases Year : 2023

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

Eric Hachulla
Marc Humbert
  • Function : Author
Christophe Guignabert
  • Function : Author
Robert Lafyatis
  • Function : Author

Abstract

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. Conclusion Chemerin 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.
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hal-03927525 , version 1 (17-01-2024)

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Sébastien Sanges, Lisa Rice, Ly Tu, Eleanor Valenzi, Jean-Luc Cracowski, et al.. Biomarkers of haemodynamic severity of systemic sclerosis-associated pulmonary arterial hypertension by serum proteome analysis. Annals of the Rheumatic Diseases, 2023, pp.ard-2022-223237. ⟨10.1136/ard-2022-223237⟩. ⟨hal-03927525⟩
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