Monica M Yang,Shuo Liu,Michael Wax,Seoyeon Lee,Sarah French,Paul J Wolters,Francesco Boin
{"title":"外周血白细胞端粒长度预测系统性硬化症的疾病严重程度和较差的生存率。","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":"{\"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}","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}
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.
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.