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. 2017 Nov;72(11):1052-1054.
doi: 10.1136/thoraxjnl-2016-209897. Epub 2017 Apr 26.

Short lung transplant donor telomere length is associated with decreased CLAD-free survival

Hilary E Faust  1   2 , Jeffrey A Golden  2 , Raja Rajalingam  2 , Angelia S Wang  2 , Gary Green  2 , Steven R Hays  2 , Jasleen Kukreja  2 , Jonathan P Singer  2 , Paul J Wolters  2 , John R Greenland  2   3
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Short lung transplant donor telomere length is associated with decreased CLAD-free survival

Hilary E Faust et al. Thorax. 2017 Nov.

Abstract

Telomere length (TL) decreases with cellular ageing and biological stressors. As advanced donor and recipient ages are risk factors for chronic lung allograft dysfunction (CLAD), we hypothesised that decreased age-adjusted donor TL would predict earlier onset of CLAD. Shorter donor TL was associated with increased risk of CLAD or death (HR 1.26 per 1 kb TL decrease, 95% CI 1.03 to 1.54), particularly for young donors. Recipient TL was associated with cytopenias but not CLAD. Shorter TL was also seen in airway epithelium for subjects progressing to CLAD (p=0.02). Allograft TL may contribute to CLAD pathogenesis and facilitate risk stratification.

Keywords: Lung Transplantation.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1:
Figure 1:. Short donor telomere length in peripheral blood and airway biopsies is associated with decreased CLAD-free survival.
(A) Telomere length in kilobases versus age in years for donors (red triangles) and recipients (blue circles). Linear regression of telomere length versus age across both cohorts resulted in a slope of −25 (95% CI −17 to −32) base pairs per year. (B) Kaplan-Meier plot showing CLAD-free survival stratified by quintiles of donor telomere length. Improved CLAD-free survival was seen across increasing quintiles of donor telomere length (P = 0.04), with improved survival in the >80%ile group compared with the <20%ile group (P = 0.02). Increasing quintile of recipient telomere length was not associated with CLAD-free survival (P = 0.59). (C) Hazard ratios for CLAD or death per 1 KB decrease in telomere length stratified by donor age under 30 (blue) or over 30 (grey) and adjusted for subject characteristics in Supplemental Table 2 are plotted against donor telomere length. Solid line shows spline fit of data with shaded area indicating 95% confidence intervals. (D-E) Quantification of telomere length in airway epithelial cells from lung transplant recipients who would either develop CLAD or remain CLAD-free. Endobronchial biopsies collected during surveillance bronchoscopy within the first 90 days post-transplant (median 31 days) were stained for telomeric DNA (red), E-cadherin (green), and total DNA (DAPI, blue). Shown are representative images from (D) a CLAD-free subject with a telomere to DAPI ratio of 40 and (E) a CLAD subject with a telomere to DAPI ratio of 15. As shown in (F), telomere length was higher in CLAD-free subjects than in subjects with CLAD (P = 0.02 by Mann Whitney test).
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References

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