Skin Gene Expression Correlates of Severity of Interstitial Lung Disease in Systemic Sclerosis

Objective We undertook this hypothesis‐generating study to identify skin transcripts correlating with severity of interstitial lung disease (ILD) in systemic sclerosis (SSc). Methods Skin biopsy samples from 59 patients enrolled in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) cohort or an open‐label imatinib study (baseline visit) were examined by global gene expression analysis using Illumina HT‐12 arrays. Skin transcripts correlating with concomitantly obtained forced vital capacity (FVC) values and the modified Rodnan skin thickness score (MRSS) were identified by quantitative trait analysis. Also, immunofluorescence staining for selected transcripts was performed in affected skin and lung tissue. Plasma levels of CCL2, soluble SELP, and soluble P‐selectin glycoprotein ligand 1 (sPSGL‐1) were examined in all patients enrolled in the GENISOS cohort (n = 266). Results Eighty‐two skin transcripts correlated significantly with FVC. This gene list distinguished patients with more severe ILD (FVC