Testing a candidate composite serum protein marker of skin severity in systemic sclerosis

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Testing a candidate composite serum protein marker of skin severity in systemic sclerosis

Roblin, Elen; Clark, Kristina EN; Beesley, Claire; Ong, Voon H; Denton, Christopher P; (2024) Testing a candidate composite serum protein marker of skin severity in systemic sclerosis. Rheumatology Advances in Practice , 8 (2) , Article rkae039. 10.1093/rap/rkae039. Green open access

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Abstract

Objectives: Using an integrated multi-omic analysis we previously derived a candidate marker that estimates mRSS and thus severity of skin involvement in systemic sclerosis. In the present study we explore technical and biological validation of this composite marker in a well characterised cohort of systemic sclerosis patients. / Methods: COMP, COL4A1, TNC and SPON1 were examined in serum samples from two independent cohorts of patients with diffuse cutaneous systemic sclerosis. The BIOPSY cohort had previously been used to derive the composite marker and MODERNISE was a novel validation cohort. Multiple regression analysis derived a formula to predict modified Rodnan Skin Score based on serum ELISA protein concentration. / Results: The serum concentration of two of the proteins—COMP and TNC—positively correlated with modified Rodnan Skin Score, particularly in early diffuse cutaneous systemic sclerosis patients. Interpretable data could not be obtained for SPON1 due to technical limitations of the ELISA. COL4A1 showed correlation with disease duration but not overall mRSS. Patients receiving mycophenolate mofetil showed lower serum concentrations of COMP, COL4A1 and TNC and a lower composite biomarker score not established on treatment. A revised ELISA-based three-protein composite formula was derived for future validation studies. / Conclusions: Although more validation is required, our findings represent a further step towards a composite serum protein assay to assess skin severity in systemic sclerosis. Future work will establish its utility as a predictive or prognostic biomarker.

Type:	Article
Title:	Testing a candidate composite serum protein marker of skin severity in systemic sclerosis
Open access status:	An open access version is available from UCL Discovery
DOI:	10.1093/rap/rkae039
Publisher version:	https://doi.org/10.1093/rap/rkae039
Language:	English
Additional information:	Copyright © The Author(s) 2024. 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:	Systemic sclerosis, Scleroderma, Modified Rodnan Skin Score, Biomarker, Proteomics
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/10189882