eprintid: 10202782 rev_number: 9 eprint_status: archive userid: 699 dir: disk0/10/20/27/82 datestamp: 2025-01-03 15:58:27 lastmod: 2025-01-03 15:58:27 status_changed: 2025-01-03 15:58:27 type: article metadata_visibility: show sword_depositor: 699 creators_name: Ross, Rebecca L creators_name: Caballero-Ruiz, Begoña creators_name: Clarke, Emily L creators_name: Kakkar, Vishal creators_name: Wasson, Christopher W creators_name: Mulipa, Panji creators_name: De Lorenzis, Enrico creators_name: Merchant, Will creators_name: Di Donato, Stefano creators_name: Rindone, Andrea creators_name: Herrick, Ariane L creators_name: Denton, Christopher P creators_name: Riobo-Del Galdo, Natalia A creators_name: Del Galdo, Francesco title: Biological hallmarks of systemic sclerosis are present in the skin and serum of patients with Very Early Diagnosis of SSc (VEDOSS) ispublished: inpress divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: G90 keywords: CXCL10, Collagen, Dermal fibroblasts, Extracellular matrix, Interferon, Systemic sclerosis, VEDOSS, autoimmune diseases, connective tissue diseases, fibrosis note: 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. 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. date: 2024-12-19 date_type: published publisher: Oxford University Press (OUP) official_url: https://doi.org/10.1093/rheumatology/keae698 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2345122 doi: 10.1093/rheumatology/keae698 pii: 7928850 lyricists_name: Denton, Christopher lyricists_id: CPDEN87 actors_name: Denton, Christopher actors_id: CPDEN87 actors_role: owner full_text_status: public publication: Rheumatology event_location: England issn: 1462-0324 citation: Ross, Rebecca L; Caballero-Ruiz, Begoña; Clarke, Emily L; Kakkar, Vishal; Wasson, Christopher W; Mulipa, Panji; De Lorenzis, Enrico; ... Del Galdo, Francesco; + view all <#> Ross, Rebecca L; Caballero-Ruiz, Begoña; Clarke, Emily L; Kakkar, Vishal; Wasson, Christopher W; Mulipa, Panji; De Lorenzis, Enrico; Merchant, Will; Di Donato, Stefano; Rindone, Andrea; Herrick, Ariane L; Denton, Christopher P; Riobo-Del Galdo, Natalia A; Del Galdo, Francesco; - view fewer <#> (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 <https://doi.org/10.1093/rheumatology%2Fkeae698>. (In press). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10202782/1/Denton_keae698.pdf