Monica M Yang,Shuo Liu,Michael Wax,Seoyeon Lee,Sarah French,Paul J Wolters,Francesco Boin
{"title":"Telomere Length of Peripheral Blood Leukocytes Predicts Disease Severity and Worse Survival in Systemic Sclerosis.","authors":"Monica M Yang,Shuo Liu,Michael Wax,Seoyeon Lee,Sarah French,Paul J Wolters,Francesco Boin","doi":"10.1002/art.43400","DOIUrl":null,"url":null,"abstract":"OBJECTIVE\r\nPeripheral 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.\r\n\r\nMETHOD\r\nPBL-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.\r\n\r\nRESULTS\r\nPBL-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).\r\n\r\nCONCLUSION\r\nShort 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.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"63 1","pages":""},"PeriodicalIF":10.9000,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Arthritis & Rheumatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/art.43400","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Arthritis & Rheumatology is the official journal of the American College of Rheumatology and focuses on the natural history, pathophysiology, treatment, and outcome of rheumatic diseases. It is a peer-reviewed publication that aims to provide the highest quality basic and clinical research in this field. The journal covers a wide range of investigative areas and also includes review articles, editorials, and educational material for researchers and clinicians. Being recognized as a leading research journal in rheumatology, Arthritis & Rheumatology serves the global community of rheumatology investigators and clinicians.