• Iulia Popescu, Hannah Mannem, Spencer A Winters, Aki Hoji, Fernanda Silveira, Emily McNally, Matthew R Pipeling, Elizabeth A Lendermon, Matthew R Morrell, Joseph M Pilewski, Vidya Sagar Hanumanthu, Yingze Zhang, Swati Gulati, Pali D Shah, Carlo J Iasella, Christopher R Ensor, Mary Armanios, and John F McDyer.
• 1 Division of Pulmonary, Allergy and Critical Care Medicine and.
• Am. J. Respir. Crit. Care Med. 2019 Feb 1; 199 (3): 362376362-376.

RationaleCytomegalovirus (CMV)-related morbidities remain one of the most common complications after lung transplantation and have been linked to allograft dysfunction, but the factors that predict high risk for CMV complications and effective immunity are incompletely understood.ObjectivesTo determine if short telomeres in idiopathic pulmonary fibrosis (IPF) lung transplant recipients (LTRs) predict the risk for CMV-specific T-cell immunity and viral control.MethodsWe studied IPF-LTRs (n = 42) and age-matched non-IPF-LTRs (n = 42) and assessed CMV outcomes. We measured lymphocyte telomere length and DNA sequencing, and assessed CMV-specific T-cell immunity in LTRs at high risk for CMV events, using flow cytometry and fluorescence in situ hybridization.Measurements And Main ResultsWe identified a high prevalence of relapsing CMV viremia in IPF-LTRs compared with non-IPF-LTRs (69% vs. 31%; odds ratio, 4.98; 95% confidence interval, 1.95-12.50; P < 0.001). Within this subset, IPF-LTRs who had short telomeres had the highest risk of CMV complications (P < 0.01) including relapsing-viremia episodes, end-organ disease, and CMV resistance to therapy, as well as shorter time to viremia versus age-matched non-IPF control subjects (P < 0.001). The short telomere defect in IPF-LTRs was associated with significantly impaired CMV-specific proliferative responses, T-cell effector functions, and induction of the major type-1 transcription factor T-bet (T-box 21;TBX21).ConclusionsBecause the short telomere defect has been linked to the pathogenesis of IPF in some cases, our data indicate that impaired CMV immunity may be a systemic manifestation of telomere-mediated disease in these patients. Identifying this high-risk subset of LTRs has implications for risk assessment, management, and potential strategies for averting post-transplant CMV morbidities.

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