One-step closer to solve the mystery of predicting disease progression in systemic sclerosis associated interstitial lung disease?

BACKGROUND: Peripheral blood leukocyte telomere length (PBL-TL) is associated with outcomes in idiopathic pulmonary fibrosis patients. Whether PBL-TL is associated with progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is unknown. METHODS: A retrospective observational cohort study was performed using prospectively collected data from 213 SSc patients followed at the University of California San Francisco (UCSF) Scleroderma Center. PBL-TL was measured by qPCR of DNA isolated from peripheral blood. Associations between PBL-TL and PFT trends in patients with SSc-ILD were assessed by longitudinal analysis using Generalized Linear Mixed Models. Findings were validated in a cohort of 61 SSc-ILD patients enrolled in the Stanford University (SU) Scleroderma Center database. RESULTS: UCSF SSc patients with ILD were found to have shorter PBL-TL compared to those without ILD (6554± 671 base pairs (bp) vs 6782 ± 698 bp, p=0.01). Shorter PBL-TL was associated with the presence of ILD (adjusted odds ratio [OR] 2.1 per 1000 bp TL decrease, 95%CI [1.25–3.70], p=0.006). PBL-TL was shorter in SSc-ILD patients lacking SSc-specific autoantibodies compared to seropositive subjects (6237± 647 bp vs 6651± 653 bp, p=0.004). Shorter PBL-TL was associated with increased risk for lung function deterioration with an average of 67 ml greater loss in FVC per year for every 1000 bp decrease in PBL-TL in the combined SSc-ILD cohorts (longitudinal analysis, adjusted model: 95% CI −104ml to −33ml, p