Abstract
BackgroundPatients with short telomere syndromes and pulmonary fibrosis have increased complications after lung transplant. However, the more general impact of donor and recipient telomere length in lung transplant has not been well characterized.MethodsThis was an observational cohort study of patients who received lung transplant at a single center between January 1st 2012 and January 31st 2015. Relative donor lymphocyte telomere length was measured and classified into long (third tertile) and short (other tertiles). Relative recipient lung telomere length was measured and classified into short (first tertile) and long (other tertiles). Outcome data included survival, need for modification of immunosuppression, liver or kidney injury, cytomegalovirus reactivation, and acute rejection.ResultsRecipient lung tissue telomere lengths were measured for 54 of the 79 patients (68.3%) who underwent transplant during the study period. Donor lymphocyte telomeres were measured for 45 (83.3%) of these recipients. Neither long donor telomere length (hazard ratio [HR] = 0.58, 95% confidence interval [CI], 0.12–2.85, p = 0.50) nor short recipient telomere length (HR = 1.01, 95% CI = 0.50–2.05, p = 0.96) were associated with adjusted survival following lung transplant. Recipients with short telomeres were less likely to have acute cellular rejection (23.5% vs. 58.8%, p = 0.02) but were not more likely to have other organ dysfunction.ConclusionsIn this small cohort, neither long donor lymphocyte telomeres nor short recipient lung tissue telomeres were associated with adjusted survival after lung transplantation. Larger studies are needed to confirm these findings.
Highlights
Telomeres are repetitive nucleotide sequences at the ends of chromosomes that become truncated with successive cellular replication
Neither long donor telomere length nor short recipient telomere length (HR = 1.01, 95% CI = 0.50–2.05, p = 0.96) were associated with adjusted survival following lung transplant
Neither long donor lymphocyte telomeres nor short recipient lung tissue telomeres were associated with adjusted survival after lung transplantation
Summary
Telomeres are repetitive nucleotide sequences at the ends of chromosomes that become truncated with successive cellular replication. Almost 30% of patients with idiopathic pulmonary fibrosis (IPF) have short telomeres with or without telomerase mutations[5]. For patients with advanced IPF associated with short telomere syndromes, lung transplantation is the only definitive treatment. These individuals, are at risk for worse outcomes following transplant both because they are more susceptible to bone marrow suppressive effects of anti-rejection medication and because of reduced extra-pulmonary organ reserve [6, 7]. Borie et al found a high rate of bone marrow failure and death following lung transplant in patients with telomerase mutations[9]. The more general impact of donor and recipient telomere length in lung transplant has not been well characterized.
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