Systemic sclerosis & Raynaud's
Biomarkers of haemodynamic severity of systemic sclerosis-associated pulmonary arterial hypertension by serum proteome analysis
Authors' 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.
Study context
- Population
- Patients with limited cutaneous SSc, no extensive ILD and no PAH-specific therapy; mostly middle-aged females with anticentromere-associated SSc
- Comparison
- SSc-PAH vs SSc without clinical evidence of PAH
- Outcome
- Serum proteins differentially expressed and correlated with PVR in SSc-PAH (1129 proteins, SOMAscan; discovery, SSc-PAH n=15)
Methodological detailsdiscovery and independent validation cohort, high-throughput proteomic assay (SOMAscan), ELISA validation, single-cell RNA-sequencing, confocal immunofluorescence
- Discovery and independent validation cohort
- High-throughput proteomic assay (SOMAscan)
- ELISA validation
- Single-cell RNA-sequencing
- Confocal immunofluorescence
Main finding
As reported in the abstract
Chemerin, correlation with pulmonary vascular resistance (PVR) (ρ), p=0.01
0.62
SET, correlation with PVR (ρ), p=0.01
0.62
Proteins differentially expressed and correlated with PVR, of 1129
2
Observational data: associations, not effects.
Further findings
- Serum chemerin by ELISA, independent validation cohort (SSc-PAH n=24) — Chemerin correlation with PVR (ρ), p=0.04 · chemerin levels significantly higher in SSc-PAH
- 0.42 · P = 0.01
Mechanistic findings
- Chemerin mRNA detected in fibroblasts, pulmonary artery smooth muscle cells (PA-SMCs)/pericytes and mesothelial cells in SSc-PAH lungs (single-cell RNA-sequencing)
- Increased expression of chemerin receptor CMKLR1 on SSc-PAH PA-SMCs (confocal immunofluorescence)
- SSc-PAH serum seemed to induce higher PA-SMC proliferation than serum from SSc without PAH; difference appeared neutralised by CMKLR1 inhibitor α-NETA
Original publication
Biomarkers of haemodynamic severity of systemic sclerosis-associated pulmonary arterial hypertension by serum proteome analysis. Ann Rheum Dis. Published 5 December 2022. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →