Peripheral blood gene expression profiling shows prognostic significance for the course of interstitial lung disease in systemic sclerosis

Objective: We used data from the placebo arm of the 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, while 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 on MMF treatment. Blood gene expression profiles might be useful prognostic/predictive biomarkers in patients with SSc-ILD.