Ross, R.L., Caballero-Ruiz, B., Clarke, E.L. et al. (11 more authors) (2024) Biological hallmarks of systemic sclerosis are present in the skin and serum of patients with Very Early Diagnosis of SSc (VEDOSS). Rheumatology. keae698. ISSN 1462-0324
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2024. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Systemic sclerosis, autoimmune diseases, fibrosis, connective tissue diseases, VEDOSS, Interferon, CXCL10, Extracellular matrix, Collagen, Dermal fibroblasts |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Inflammatory Arthritis (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Medical Research (LIMR) > Division of Molecular Medicine |
Funding Information: | Funder Grant number Scleroderma & Raynaud's UK UL1 |
Depositing User: | Symplectic Publications |
Date Deposited: | 15 Jan 2025 14:09 |
Last Modified: | 15 Jan 2025 14:09 |
Status: | Published online |
Publisher: | Oxford University Press (OUP) |
Identification Number: | 10.1093/rheumatology/keae698 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:221823 |