Work

Circulating biomarkers reflect distinct quantitative CT-defined features of systemic sclerosis-associated interstitial lung disease

Year: 2026

Type: article

Abstract: Background Interstitial lung disease (ILD) is a major determinant of morbidity and mortality in systemic sclerosis (SSc). Automated quantitative CT (qCT) enables reproducible assessment of ILD extent and parenchymal texture composition. Whether circulating biomarkers reflect distinct qCT-defined features of SSc-ILD remains insufficiently characterised.Objectives To determine whether circulating biomarkers are associated with ILD presence, qCT-derived disease burden and radiological pattern composition in patients with SSc.Methods In this cross-sectional study, consecutive patients with SSc underwent same-day serum sampling and high-resolution CT. ILD presence was assessed visually, while qCT quantified ground-glass opacities (GGO), fibrotic abnormalities and total ILD extent (%). Serum levels of Krebs von den Lungen-6 (KL-6), C-C motif chemokine ligand 18 (CCL-18), surfactant protein D (SP-D), interleukin (IL)-33, IL-11, IL-25 and matrix metalloproteinase 12 (MMP-12) were measured using commercial ELISA assays.Results Eighty-two patients were included; 59 (72%) had ILD on CT. KL-6, CCL-18 and SP-D levels were significantly higher in patients with ILD, with KL-6 remaining independently associated with ILD presence in multivariable analysis. KL-6 showed the strongest associations with qCT measures of disease burden, including total ILD extent, GGO and fibrotic abnormalities. CCL-18 was associated with total ILD extent and GGO. SP-D was linked to ILD presence but not to qCT-derived measures of disease burden. IL-25 showed a preliminary association with the GGO-to-fibrosis ratio and was higher in patients with a GGO-predominant qCT pattern. IL-33, IL-11 and MMP-12 did not show significant associations with ILD presence or qCT-derived lung involvement.Conclusions Circulating biomarkers showed distinct associations with SSc-ILD presence and qCT-defined disease burden. IL-25 may also reflect radiological pattern composition, warranting validation in independent cohorts.

Source: RMD Open

DOI: 10.1136/rmdopen-2026-006938