Peripheral Blood Gene Expression Profiling and Prognostic Significance for the Course of Interstitial Lung Disease in Patients With Systemic Sclerosis

Authors

• Shervin Assassi
• Christopher P Denton
• Matthias Zwick
• Ramona Schmid
• Carina Ittrich
• Tobias Litzenburger
• Sudha Visvanathan

Language

English

Publication Date

12-1-2025

Journal

Arthritis & Rheumatology

DOI

10.1002/art.43262

PMID

40420438

PMCID

PMC12750129

PubMedCentral® Posted Date

7-29-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Objective: We used data from the placebo arm of the Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) trial to determine the prognostic/predictive significance of peripheral blood cell (PBC) transcript modules for the course of forced vital capacity (FVC) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) with and without mycophenolate mofetil (MMF) treatment.

Methods: Patients had SSc-ILD with first non-Raynaud symptom within 7 years. MMF treatment was permitted if taken at a stable dose for ≥6 months. PBC RNA samples were taken at baseline. Global RNA sequencing was performed, followed by a modular analysis using 62 curated whole blood modules. The prognostic significance of baseline composite modular scores for decline in FVC% predicted at week 52 was analyzed using mixed models for repeated measures.

Results: Among patients taking MMF (n = 120), higher baseline lymphoid lineage and mitochondrial/protein synthesis modules were associated with a better course of FVC% predicted, whereas higher baseline myeloid lineage and inflammation modules were associated with a faster decline in FVC% predicted. Among patients not taking MMF (n = 118), only myeloid lineage and inflammation modules were associated with a faster decline in FVC% predicted.

Conclusion: Among patients with SSc-ILD in the SENSCIS trial, PBC modules involved in myeloid lineage were associated with a faster decline in FVC regardless of MMF treatment. Higher baseline lymphoid, protein synthesis, and mitochondrial module scores were associated with a better course of SSc-ILD among patients receiving MMF treatment. Blood gene expression profiles might be useful prognostic/predictive biomarkers in patients with SSc-ILD.

Keywords

Adult, Aged, Female, Humans, Male, Middle Aged, Gene Expression Profiling, Immunosuppressive Agents, Indoles, Lung Diseases, Interstitial, Mycophenolic Acid, Prognosis, Scleroderma, Systemic, Vital Capacity

Published Open-Access

yes

Recommended Citation

Assassi, Shervin; Denton, Christopher P; Zwick, Matthias; et al., "Peripheral Blood Gene Expression Profiling and Prognostic Significance for the Course of Interstitial Lung Disease in Patients With Systemic Sclerosis" (2025). Faculty, Staff and Student Publications. 3537.
https://digitalcommons.library.tmc.edu/uthmed_docs/3537