Lung transplantation for idiopathic pulmonary fibrosis enriches for individuals with telomere-mediated disease

作者：Jonathan K. Alder, Rachel M. Sutton, Carlo J. Iasella, Mehdi syed Nouraie, Ritchie Koshy, Stefanie J. Hannan, Ernest G. Chan, Xiaoping Chen, Yingze Zhang, Mark J. Brown, Iulia Popescu, Melinda Veatch, Melissa I. Saul, Annerose Berndt, Barbara A. Methé, Alison M. Morris, Joseph M. Pilewski, Pablo Gerardo Sánchez, Matthew R. Morrell, Steven David Shapiro, Kathleen Oare Lindell, Kevin F. Gibson, Daniel J. Kass, John F. McDyer · 发表于：The Journal of Heart and Lung Transplantation · 年份：2021 · DOI：10.1016/j.healun.2021.11.008 · 被引用次数：51 · 研究领域：Telomeres, Telomerase, and Senescence、Transplantation: Methods and Outcomes、Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common indication for lung transplantation in North America and variants in telomere-maintenance genes are the most common identifiable cause of IPF. We reasoned that younger IPF patients are more likely to undergo lung transplantation and we hypothesized that lung transplant recipients would be enriched for individuals with telomere-mediated disease due to the earlier onset and more severe disease in these patients. METHODS: Individuals with IPF who underwent lung transplantation or were evaluated in an interstitial lung disease specialty clinic who did not undergo lung transplantation were examined. Genetic evaluation was completed via whole genome sequencing (WGS) of 426 individuals and targeted sequencing for 5 individuals. Rare variants in genes previously associated with IPF were classified using the American College of Medical Genetics guidelines. Telomere length from WGS data was measured using TelSeq software. Patient characteristics were collected via medical record review. RESULTS: Of 431 individuals, 149 underwent lung transplantation for IPF. The median age of diagnosis of transplanted vs non-transplanted individuals was significantly younger (60 years vs 70 years, respectively, p<0.0001). IPF lung transplant recipients (IPF-LTRs) were twice as likely to have telomere-related rare variants compared to non-transplanted individuals (24% vs 12%, respectively, p=0.0013). IPF-LTRs had shorter telomeres than n...