Evidence map›Paper›PMID 39700423›Full record

ArticleRheumatology (Oxford, England)2025

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

Rebecca L Ross, Begoña Caballero-Ruiz, Emily L Clarke, Vishal Kakkar, Christopher W Wasson, Panji Mulipa, Enrico De Lorenzis, Will Merchant, Stefano Di Donato, Andrea Rindone and 4 more

Abstract read
In one paragraph

Article in Rheumatology (Oxford, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Rebecca L RossLeeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.ORCID 0000-0001-7750-4280
Begoña Caballero-RuizLeeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
Emily L ClarkeSection of Pathology and Tumour Biology, University of Leeds, Leeds, UK.
Vishal KakkarLeeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
Christopher W WassonLeeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
Panji MulipaLeeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
Enrico De LorenzisLeeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.ORCID 0000-0001-9819-105X
Will MerchantLeeds Teaching Hospitals, NHS Trust, St James's University Hospital, Leeds, UK.
Stefano Di DonatoLeeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
Andrea RindoneLeeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
Ariane L HerrickDivision of Musculoskeletal & Dermatological Sciences, The University of Manchester, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.ORCID 0000-0003-4941-7926
Christopher P DentonCentre for Rheumatology, Division of Medicine, University College London, London, UK.ORCID 0000-0003-3975-8938
Natalia A Riobo-Del GaldoSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK.
Francesco Del GaldoLeeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.ORCID 0000-0002-8528-2283

Funding

Alan Turing InstituteCare Research Biomedical Research CentreDepartment of Health and Social CareKennedy Trust Program FoundationLeeds Biomedical Research Centre NIHR203331Manchester Biomedical Research Centre NIHR203308Medical Research Council MR/S001530/1National Institute for HealthNational Institute for Health and Care ResearchNIHR NIHR213331SRUKSusan Cheney Scleroderma Research Foundation
6 · The paper itself

Abstract

objectiveThe 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.

methodsSkin 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.

resultsOverall, 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).

conclusionsDespite 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.

Indexed as

Chemokine CXCL10Scleroderma, SystemicSkinAdultAgedBiomarkersBiopsyCase-Control StudiesDisease ProgressionEarly DiagnosisFemaleFibroblastsHumansMaleMiddle AgedBiomarkersChemokine CXCL10CXCL10 protein, humanautoimmune diseasescollagenconnective tissue diseasesCXCL10dermal fibroblastsextracellular matrixfibrosisinterferonsystemic sclerosisVEDOSS

Identifiers

PMID39700423
PMCPMC12107078

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.