Ross, Rebecca L;
Caballero-Ruiz, Begoña;
Clarke, Emily L;
Kakkar, Vishal;
Wasson, Christopher W;
Mulipa, Panji;
De Lorenzis, Enrico;
... Del Galdo, Francesco; + view all
(2024)
Biological hallmarks of systemic sclerosis are present in the skin and serum of patients with Very Early Diagnosis of SSc (VEDOSS).
Rheumatology
10.1093/rheumatology/keae698.
(In press).
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Abstract
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 antinuclear antibodies and/or capillaroscopy abnormalities often progress to systemic sclerosis (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 [SD]; 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 (IQR 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.
| Type: | Article |
|---|---|
| Title: | Biological hallmarks of systemic sclerosis are present in the skin and serum of patients with Very Early Diagnosis of SSc (VEDOSS) |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/rheumatology/keae698 |
| Publisher version: | https://doi.org/10.1093/rheumatology/keae698 |
| Language: | English |
| Additional information: | Copyright © The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | CXCL10, Collagen, Dermal fibroblasts, Extracellular matrix, Interferon, Systemic sclerosis, VEDOSS, autoimmune diseases, connective tissue diseases, fibrosis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10202782 |
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