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

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.