Systemic sclerosis & Raynaud's
Clinical and pathogenic significance of S100A4 overexpression in systemic sclerosis
Authors' conclusion
Our findings provide compelling evidence for a profibrotic role for S100A4 in SSc and suggest that serum level may be a biomarker of major organ manifestations and disease severity.
Study context
- Population
- Patients with systemic sclerosis (SSc) and healthy controls; skin fibroblast cultures from dcSSc and healthy controls
- Participants
- 94 / 15 / 6 / 6
- Comparison
- SSc vs healthy controls (serum S100A4); SSc fibroblasts vs normal fibroblasts; anti-S100A4 antibody AX-202 on fibroblasts
- SScn = 94
- Healthy controlsn = 15reference
- SScFn = 6
- Normal fibroblasts (NF)n = 6reference
- Outcome
- Serum S100A4 concentration (ELISA)
Methodological detailscase-control serum comparison, in vitro fibroblast cultures, genome-wide RNA sequencing
- Case-control serum comparison
- In vitro fibroblast cultures
- Genome-wide RNA sequencing
Main finding
As reported in the abstract
Serum S100A4 (ng/mL), median (range)
P = 0.027
Further findings
Median, ng/mL
| Outcome | SScF | NF | P value |
|---|---|---|---|
| S100A4 (ng/mL) in culture supernatants, median (range)SScF vs NF · higher in SScF | 4.19 (range 0.52–8.42) | 0.28 (range 0.02–3.29) | P < 0.0001 |
Association of serum S100A4 with SSc-ILD
- Association with SSc-ILD (n=55)
- P = 0.025
Association of serum S100A4 with scleroderma renal crisis
- Association with scleroderma renal crisis (n=4)
- P = 0.026
Effect of AX-202 on SScF
- AX-202 reduced the constitutive profibrotic gene and protein expression phenotype of SScF
RNA sequencing: S100A4-dependent genes
- Differentially expressed genes induced in NF by S100A4, also constitutively overexpressed and downregulated by AX-202 in SScF (false discovery rate (FDR) <0.001, fold change (FC) >1.5)
- 464
- Kegg pathway enrichment: regulation of stem cell pluripotency (FDR <0.001)
- 4.6-fold
- Kegg pathway enrichment: metabolic pathways (FDR <0.001)
- 1.9-fold
Original publication
Clinical and pathogenic significance of S100A4 overexpression in systemic sclerosis. Ann Rheum Dis. Published 6 July 2023. doi:10.
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