Abstract

BACKGROUND: Peripheral blood leucocyte telomere length (PBL-TL) is associated with outcomes in patients with idiopathic pulmonary fibrosis. 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 patients with SSc followed at the University of California San Francisco (UCSF) Scleroderma Center. PBL-TL was measured by quantitative PCR of DNA isolated from peripheral blood. Associations between PBL-TL and pulmonary function test trends in patients with SSc-ILD were assessed by longitudinal analysis using Generalised Linear Mixed Models. Findings were validated in a cohort of 61 patients with SSc-ILD enrolled in the Stanford University Scleroderma Center database.RESULTS: Patients with UCSF SSc with ILD were found to have shorter PBL-TL compared with those without ILD (6554±671base pairs (bp) vs 6782±698bp, p=0.01). Shorter PBL-TL was associated with the presence of ILD (adjusted OR 2.1 per 1000bp TL decrease, 95%CI [1.25 to 3.70], p=0.006). PBL-TL was shorter in patients with SSc-ILD lacking SSc-specific autoantibodies compared with seropositive subjects (6237±647bp vs 6651±653bp, p=0.004). Shorter PBL-TL was associated with increased risk for lung function deterioration with an average of 67mL greater loss in per year for every 1000bp decrease in PBL-TL in the combined SSc-ILD cohorts (longitudinal analysis, adjusted model: 95%CI -104 mL to -33mL, p<0.001).CONCLUSIONS: These findings suggest that telomere dysfunction may be associated with SSc-ILD progression and that PBL-TL measurement may be useful for stratifying risk for SSc-ILD progression.

View details for DOI 10.1136/thoraxjnl-2020-215918

View details for PubMedID 34272332