Biological hallmarks of systemic sclerosis are present in the skin and serum of patients with Very Early Diagnosis of Systemic Sclerosis (VEDOSS).

OBJECTIVE

The Very Early Diagnosis of Systemic Sclerosis (VEDOSS) EUSTAR study showed that, despite not showing any clinical sign of disease, patients with Raynaud's and ANA and/or capillaroscopy abnormalities often progress to SSc within 5 years. We aimed to determine whether VEDOSS biosamples show biological SSc activity pre-clinically.

METHODS

Skin biopsies were histologically analysed. Dermal fibroblasts analysed by RT-qPCR and gel contraction assays. Sera were assayed by Luminex (CXCL10) or ELISA (ELF score). Healthy controls (HC) and SSc biosamples were used for controls.

RESULTS

Overall, 114 consecutive VEDOSS patients were enrolled, of which 36 consented to have skin biopsies. Skin biopsies showed a variable but overall increased collagen staining and skin thickness, increased perivascular infiltrate of CD45-positive cells and CXCL10 expression. In vitro, VEDOSS dermal fibroblasts showed increased profibrotic gene expression and contractibility compared with HC. Increased serological CXCL10 [mean (s.d.) 75.90 (107.80) vs HC 39.90 (26.27) pg/ml, P = 0.02] and ELF score was evident in VEDOSS compared with HC [8.19 (0.78) vs 8.55 (0.79), P = 0.04]. In longitudinal analysis of a median of 27.5 (interquartile range 44.5) months, 14.9% of VEDOSS patients progressed to SSc. Baseline CXCL10 serum concentration was significantly higher in the VEDOSS patients that progressed (2-fold increase, P = 0.0071) and correlated with ELF score (R = 0.3096, P = 0.0065).

CONCLUSIONS

Despite not fulfilling classification criteria, VEDOSS patients show SSc-linked fibrosis and immunity dysregulation both within the tissue and sera, supporting a biological diagnosis of disease and a window of opportunity to detect the biological pathways amenable for preventive intervention.