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Peer-reviewedCC BYRMD Open

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

  • Fabrizio Conti1
  • Valeria Riccieri1
  • Greta Pellegrino2
  • Valeria Panebianco3
  • Simona Truglia1
  • Marius Cadar1
  • Nicholas Landini3
  • Martina Salerno1
  • Ilaria Bisconti1
  • Elena Platania1
  • Jacopo Landro1
  • Francesca Romana Di Ciommo1
5 more authors
  • Giuseppe Ocone4
  • Loredana Frasca4
  • Davide Mohammad Reza Beigi1
  • Giada La Spina1
  • Gregorino Paone5
5 affiliations
  1. 1Dipartimento di Scienze Mediche e Cardiovascolari, Rheumatology Unit, Sapienza University of Rome, Rome, Italy
  2. 2IRCCS Ospedale Galeazzi - Sant`Ambrogio, Milan, Italy
  3. 3Department of Radiological, Oncological and Pathological Sciences, “Sapienza” University of Rome, Policlinico Umberto I Hospital, Rome, Italy
  4. 4Istituto Superiore di Sanità, National Center for Global Health, Rome, Italy
  5. 5Dipartimento di Scienze Mediche e Cardiovascolari, Respiratory Medicine Unit, Sapienza University of Rome, Rome, Italy
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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.

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BibTeXRIS
BibTeX
@article{conti2026circulating,
  title = {{Circulating biomarkers reflect distinct quantitative CT-defined features of systemic sclerosis-associated interstitial lung disease}},
  author = {Fabrizio Conti and Valeria Riccieri and Greta Pellegrino and Valeria Panebianco and Simona Truglia and Marius Cadar and Nicholas Landini and Martina Salerno and Ilaria Bisconti and Elena Platania and Jacopo Landro and Francesca Romana Di Ciommo and Giuseppe Ocone and Loredana Frasca and Davide Mohammad Reza Beigi and Giada La Spina and Gregorino Paone},
  journal = {RMD Open},
  year = {2026},
  month = nov,
  doi = {10.1136/rmdopen-2026-006938},
  url = {https://doi.org/10.1136/rmdopen-2026-006938},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Circulating biomarkers reflect distinct quantitative CT-defined features of systemic sclerosis-associated interstitial lung disease
AU  - Fabrizio Conti
AU  - Valeria Riccieri
AU  - Greta Pellegrino
AU  - Valeria Panebianco
AU  - Simona Truglia
AU  - Marius Cadar
AU  - Nicholas Landini
AU  - Martina Salerno
AU  - Ilaria Bisconti
AU  - Elena Platania
AU  - Jacopo Landro
AU  - Francesca Romana Di Ciommo
AU  - Giuseppe Ocone
AU  - Loredana Frasca
AU  - Davide Mohammad Reza Beigi
AU  - Giada La Spina
AU  - Gregorino Paone
PY  - 2026
DA  - 2026/11/08
JO  - RMD Open
DO  - 10.1136/rmdopen-2026-006938
UR  - https://doi.org/10.1136/rmdopen-2026-006938
AB  - 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.
SN  - 2056-5933
ER  -