TY - JOUR
T1 - Use of donor-derived-cell-free DNA as a marker of early allograft injury in primary graft dysfunction (PGD) to predict the risk of chronic lung allograft dysfunction (CLAD)
AU - Keller, Michael
AU - Bush, Errol
AU - Diamond, Joshua M.
AU - Shah, Pali
AU - Matthew, Joby
AU - Brown, Anne W.
AU - Sun, Junfeng
AU - Timofte, Irina
AU - Kong, Hyesik
AU - Tunc, Ilker
AU - Luikart, Helen
AU - Iacono, Aldo
AU - Nathan, Steven D.
AU - Khush, Kiran K.
AU - Orens, Jonathan
AU - Jang, Moon
AU - Agbor-Enoh, Sean
N1 - Funding Information:
Dr. Errol Bush has received consulting fees from VeraMedica Institute for occupational/environmental exposure litigation. Dr. Kiran Khush reports receiving grants and personal fees as a scientific advisor and participant on a speaker's bureau from CareDx Inc. outside of the scope of the submitted work. Dr. Sean Agbor-Enoh receives funding from the Cystic Fibrosis Foundation, the National Institute of Health Distinguished Scholar Program and the National Heart, Lung and Blood Institute Intramural Research division.
Funding Information:
The Genome Transplant Dynamics Study ( NCT01985412 ) is funded by the National Institutes of Health , Grant RC4AI092673 . The Genomic Research Alliance for Transplantation Study ( NCT02423070 ) is funded by the Division of Intramural Research of the National Heart, Lung, and Blood Institute. Funders had no role in study design, data collection, data analysis, interpretation, writing of the report.
Publisher Copyright:
© 2021
PY - 2021/6
Y1 - 2021/6
N2 - BACKGROUND: Primary graft dysfunction (PGD) is a risk factor for chronic lung allograft dysfunction (CLAD). However, the association between PGD and degree of allograft injury remains poorly defined. In this study, we leverage a novel biomarker for allograft injury, percentage donor-derived cell-free DNA (%ddcfDNA), to study the association between PGD, degree of allograft injury, and the development of CLAD. METHODS: This prospective cohort study recruited 99 lung transplant recipients and collected plasma samples on days 1, 3, and 7 for %ddcfDNA measurements. Clinical data on day 3 was used to adjudicate for PGD. %ddcfDNA levels were compared between PGD grades. In PGD patients, %ddcfDNA was compared between those who developed CLAD and those who did not. RESULTS: On posttransplant day 3, %ddcfDNA was higher in PGD than in non-PGD patients (median [IQR]: 12.2% [8.2, 22.0] vs 8.5% [5.6, 13.2] p = 0.01). %ddcfDNA correlated with the severity grade of PGD (r = 0.24, p = 0.02). Within the PGD group, higher levels of %ddcfDNA correlated with increased risk of developing CLAD (log OR(SE) 1.38 (0.53), p = 0.009). PGD patients who developed CLAD showed ∼2-times higher %ddcfDNA levels than patients who did not develop CLAD (median [IQR]: 22.4% [11.8, 27.6] vs 9.9% [6.7, 14.9], p = 0.007). CONCLUSION: PGD patients demonstrated increased early posttransplant allograft injury, as measured by %ddcfDNA, in comparison to non-PGD patients, and these high %ddcfDNA levels were associated with subsequent development of CLAD. This study suggests that %ddcfDNA identifies PGD patients at greater risk of CLAD than PGD alone.
AB - BACKGROUND: Primary graft dysfunction (PGD) is a risk factor for chronic lung allograft dysfunction (CLAD). However, the association between PGD and degree of allograft injury remains poorly defined. In this study, we leverage a novel biomarker for allograft injury, percentage donor-derived cell-free DNA (%ddcfDNA), to study the association between PGD, degree of allograft injury, and the development of CLAD. METHODS: This prospective cohort study recruited 99 lung transplant recipients and collected plasma samples on days 1, 3, and 7 for %ddcfDNA measurements. Clinical data on day 3 was used to adjudicate for PGD. %ddcfDNA levels were compared between PGD grades. In PGD patients, %ddcfDNA was compared between those who developed CLAD and those who did not. RESULTS: On posttransplant day 3, %ddcfDNA was higher in PGD than in non-PGD patients (median [IQR]: 12.2% [8.2, 22.0] vs 8.5% [5.6, 13.2] p = 0.01). %ddcfDNA correlated with the severity grade of PGD (r = 0.24, p = 0.02). Within the PGD group, higher levels of %ddcfDNA correlated with increased risk of developing CLAD (log OR(SE) 1.38 (0.53), p = 0.009). PGD patients who developed CLAD showed ∼2-times higher %ddcfDNA levels than patients who did not develop CLAD (median [IQR]: 22.4% [11.8, 27.6] vs 9.9% [6.7, 14.9], p = 0.007). CONCLUSION: PGD patients demonstrated increased early posttransplant allograft injury, as measured by %ddcfDNA, in comparison to non-PGD patients, and these high %ddcfDNA levels were associated with subsequent development of CLAD. This study suggests that %ddcfDNA identifies PGD patients at greater risk of CLAD than PGD alone.
KW - Chronic lung allograft dysfunction (CLAD)
KW - Donorderived cell-free DNA (ddcfDNA)
KW - Primary graft dysfunction (PGD)
KW - Rejection
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U2 - 10.1016/j.healun.2021.02.008
DO - 10.1016/j.healun.2021.02.008
M3 - Article
C2 - 33814284
AN - SCOPUS:85103553559
SN - 1053-2498
VL - 40
SP - 488
EP - 493
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 6
ER -