Abstract Background/Aims Skin fibrosis is a cardinal manifestation of systemic sclerosis (SSc) and is measured by modified Rodnan skin score (mRSS), which is however limited by its operator-dependence and may not reflect the complex biology at the cutaneous compartment. A recent multi-omic analysis identified 3 serum proteins independently associated with mRSS: tenascin C (TENC), cartilage oligomeric matrix protein (COMP), and collagen type IV alpha 1 (COL4A1). The aim of our study was to evaluate the relationship between these analytes as biomarkers for skin involvement, as well as to capture potential correlations with immunosuppressive treatment. Methods We selected 21 patients who participated in the Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial - a phase 3, multicentre, randomized study comparing autologous stem cell transplantation (HSCT) to cyclophosphamide (CYC) in diffuse cutaneous (dc)SSc. Serum concentrations of the analytes were measured with ELISAs at baseline, 12 and 24 months. We employed linear mixed-effects models to assess cross-sectional correlation between mRSS, analyte concentrations and time. A multivariable linear regression model (independent of time) was used to formulate a composite biomarker score to predict mRSS. Results We included 11 patients in the CYC arm, and 10 in the HSCT arm. Serum concentrations of COMP and COL4A1, but not TENC, showed significant correlation with mRSS at the mixed model, with COL4A1 retaining significance at multivariable analysis (β = 0.01, p = 0.001). We derived a composite biomarker formula score to predict mRSS with good performance at Bland Altman plot. As dynamic biomarkers, only changes in concentrations of COMP were associated with mRSS change (r = 0.013; p = 0.012). Notably, there was greater reduction in COL4A1 concentration at 24 months in the HSCT group compared with CYC (-81 ng/mL vs -27.4 ng/mL in CYC group; p = 0.029). Conclusion Our composite biomarker score showed good cross-sectional correlation with mRSS and could potentially complement mRSS in the assessment of skin activity. The differential variations for serum COL4A1 across treatment groups warrant further evaluation as a predictive marker of immunotherapeutic response in dcSSc. Disclosure S. Rodolfi: None. K.E. Clark: None. B. Ahmed Abdi: None. E. Roblin: None. M. Kanitkar: None. V.H. Ong: None. A.E. Voskuyl: None. J.K. De Vries-Bouwstra: None. J.M. van Laar: None. C.P. Denton: None. J. Spierings: None.
Rodolfi et al. (2026) studied this question.
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