Peripheral blood leucocyte telomere length is associated with progression of interstitial lung disease in systemic sclerosis. Thorax Liu, S., Chung, M. P., Ley, B., French, S., Elicker, B. M., Fiorentino, D. F., Chung, L. S., Boin, F., Wolters, P. J. 2021


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