BACKGROUND: Pulmonary fibrosis (PF) is the most common disease indication for lung transplantation. Our recent work implicated an excess of rare genetic variants in the telomere-related genes TERT, RTEL1, and PARN in PF disease risk. The impact of such variants on posttransplant outcomes is uncertain. The objective of this study was to determine if patients with these PF-associated variants have altered rates of posttransplant acute rejection (AR), chronic lung allograft dysfunction (CLAD), and survival. METHODS: The study cohort consisted of 262 PF lung transplant recipients previously genetically characterized by whole exome sequencing. Thirty-one patients (11.8%) had variants in TERT, RTEL1, or PARN, whereas 231 (88.2%) did not. Multivariate Cox proportional hazards models adjusted for relevant clinical variables were used to assess the outcomes of death and CLAD. The AR burden was quantified and compared over the first posttransplant year. RESULTS: Patients with PF with disease-associated variants in TERT, RTEL1, or PARN had a significantly higher risk of death (adjusted hazard ratio [HR], 1.82; 95% CI, 1.07-3.08; P = .03) and CLAD (adjusted HR, 2.88; 95% CI, 1.42-5.87; P = .004) than patients without these variants. There was no difference in AR burden or rates of grade 3 primary graft dysfunction between the two groups. CONCLUSIONS: Rare variants in the telomere-related genes TERT, RTEL1, or PARN are associated with poor posttransplant outcomes among PF lung transplant recipients. Further research is needed to understand the biological mechanisms by which telomere-related variants increase the risk for death and CLAD. Published by Elsevier Inc.
BACKGROUND:Pulmonary fibrosis (PF) is the most common disease indication for lung transplantation. Our recent work implicated an excess of rare genetic variants in the telomere-related genes TERT, RTEL1, and PARN in PF disease risk. The impact of such variants on posttransplant outcomes is uncertain. The objective of this study was to determine if patients with these PF-associated variants have altered rates of posttransplant acute rejection (AR), chronic lung allograft dysfunction (CLAD), and survival. METHODS: The study cohort consisted of 262 PF lung transplant recipients previously genetically characterized by whole exome sequencing. Thirty-one patients (11.8%) had variants in TERT, RTEL1, or PARN, whereas 231 (88.2%) did not. Multivariate Cox proportional hazards models adjusted for relevant clinical variables were used to assess the outcomes of death and CLAD. The AR burden was quantified and compared over the first posttransplant year. RESULTS:Patients with PF with disease-associated variants in TERT, RTEL1, or PARN had a significantly higher risk of death (adjusted hazard ratio [HR], 1.82; 95% CI, 1.07-3.08; P = .03) and CLAD (adjusted HR, 2.88; 95% CI, 1.42-5.87; P = .004) than patients without these variants. There was no difference in AR burden or rates of grade 3 primary graft dysfunction between the two groups. CONCLUSIONS: Rare variants in the telomere-related genes TERT, RTEL1, or PARN are associated with poor posttransplant outcomes among PF lung transplant recipients. Further research is needed to understand the biological mechanisms by which telomere-related variants increase the risk for death and CLAD. Published by Elsevier Inc.
Authors: Neha Nagpal; Jianing Wang; Jing Zeng; Emily Lo; Diane H Moon; Kevin Luk; Roman O Braun; Lauri M Burroughs; Sioban B Keel; Christopher Reilly; R Coleman Lindsley; Scot A Wolfe; Albert K Tai; Patrick Cahan; Daniel E Bauer; Yick W Fong; Suneet Agarwal Journal: Cell Stem Cell Date: 2020-04-21 Impact factor: 24.633
Authors: Lorriana E Leard; Are M Holm; Maryam Valapour; Allan R Glanville; Sandeep Attawar; Meghan Aversa; Silvia V Campos; Lillian M Christon; Marcelo Cypel; Göran Dellgren; Matthew G Hartwig; Siddhartha G Kapnadak; Nicholas A Kolaitis; Robert M Kotloff; Caroline M Patterson; Oksana A Shlobin; Patrick J Smith; Amparo Solé; Melinda Solomon; David Weill; Marlies S Wijsenbeek; Brigitte W M Willemse; Selim M Arcasoy; Kathleen J Ramos Journal: J Heart Lung Transplant Date: 2021-07-24 Impact factor: 13.569
Authors: Jonathan K Alder; Rachel M Sutton; Carlo J Iasella; Mehdi Nouraie; Ritchie Koshy; Stefanie J Hannan; Ernest G Chan; Xiaoping Chen; Yingze Zhang; Mark Brown; Iulia Popescu; Melinda Veatch; Melissa Saul; Annerose Berndt; Barbara A Methé; Alison Morris; Joseph M Pilewski; Pablo G Sanchez; Matthew R Morrell; Steven D Shapiro; Kathleen O Lindell; Kevin F Gibson; Daniel J Kass; John F McDyer Journal: J Heart Lung Transplant Date: 2021-11-15 Impact factor: 13.569
Authors: Ping Wang; Joey Leung; Alice Lam; Seoyeon Lee; Daniel R Calabrese; Steven R Hays; Jeffery A Golden; Jasleen Kukreja; Jonathan P Singer; Paul J Wolters; Qizhi Tang; John R Greenland Journal: J Heart Lung Transplant Date: 2021-11-25 Impact factor: 13.569
Authors: Andrew M Courtwright; Anthony M Lamattina; Mai Takahashi; Anil J Trindade; Gary M Hunninghake; Ivan O Rosas; Suneet Agarwal; Benjamin A Raby; Hilary J Goldberg; Souheil El-Chemaly Journal: ERJ Open Res Date: 2020-06-15
Authors: Philip L Molyneaux; Adam Platt; Slavé Petrovski; Ryan S Dhindsa; Johan Mattsson; Abhishek Nag; Quanli Wang; Louise V Wain; Richard Allen; Eleanor M Wigmore; Kristina Ibanez; Dimitrios Vitsios; Sri V V Deevi; Sebastian Wasilewski; Maria Karlsson; Glenda Lassi; Henric Olsson; Daniel Muthas; Susan Monkley; Alex Mackay; Lynne Murray; Simon Young; Carolina Haefliger; Toby M Maher; Maria G Belvisi; Gisli Jenkins Journal: Commun Biol Date: 2021-03-23