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

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.