Telomere Length of Peripheral Blood Leukocytes Predicts Disease Severity and Worse Survival in Systemic Sclerosis

Objective Peripheral blood leukocyte telomere length (PBL‐TL) shortening is associated with systemic sclerosis related interstitial lung disease (SSc‐ILD). However, its association with other organ involvement, disease severity, and survival remains unclear. This study aimed to define the relationship of TL with SSc‐specific disease manifestations and outcomes. Method PBL‐TL was measured by quantitative PCR in 244 patients with SSc and 314 healthy controls. Multivariate modeling was utilized to assess the association of PBL‐TL with disease severity and event‐free survival. Longitudinal changes in PBL‐TL were measured in a subset of patients. Telomere length was quantified in SSc skin and lung tissues by telomere fluorescence in situ hybridization. Results PBL‐TL was significantly shorter in patients with SSc than healthy controls. Shortened PBL‐TL was associated with presence and severity of ILD and pulmonary hypertension (PH) with the shortest PBL‐TL found in subjects with concurrent ILD and PH (p=0.04). PBL‐TL was not associated with skin disease or peripheral vascular disease. Shorter PBL‐TL was associated with hospitalizations (p<0.01) and worse event‐free survival (p=0.03). Patients with early SSc had a faster rate of PBL‐TL shortening compared to patients with longer disease duration (p = 0.04). TL was shorter in SSc‐ILD lung epithelial cells (p=0.01) while no difference was found in epithelial cells of SSc skin (p=0.82). Conclusion Short PBL‐TL is associated with pulmonary disease severity and predicts worse SSc clinical outcomes. This study provides rationale to further investigate the role of telomere dysfunction in SSc pathogenesis and validate TL as a prognostic biomarker in SSc.