Variability in plasma donor-derived cell-free DNA levels with CLAD more than 5-years after Lung Transplantation: Pilot data
Background: Chronic lung allograft dysfunction (CLAD) is a highly prevalent and devastating complication in lung transplant (LT), culminating in increased allograft failure, morbidity, and mortality. Determination of the fraction of plasma donor-derived cell-free DNA (dd-cfDNA) has emerged as a valu...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Transplantation Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2451959622000142 |
| _version_ | 1798032301028802560 |
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| author | Deborah Jo Levine Zachary P. Demko David J. Ross |
| author_facet | Deborah Jo Levine Zachary P. Demko David J. Ross |
| author_sort | Deborah Jo Levine |
| collection | DOAJ |
| description | Background: Chronic lung allograft dysfunction (CLAD) is a highly prevalent and devastating complication in lung transplant (LT), culminating in increased allograft failure, morbidity, and mortality. Determination of the fraction of plasma donor-derived cell-free DNA (dd-cfDNA) has emerged as a valuable noninvasive monitoring tool after LT; however, the increased variance of host cfDNA caused by infection and other inflammation can complicate the approach. Methods: In a retrospective pilot study, we analyzed both the fraction of dd-cfDNA (%dd-cfDNA) and absolute quantity of dd-cfDNA (cp/mL) in recipients with CLAD ≥ 5-year post-LT with co-morbid conditions (gastro-esophageal reflux, antibody-mediated rejection, or chronic infection) designated as complicated (C-CLAD) and uncomplicated (U-CLAD) cohorts. Results: Median time post-LT was 2,149 days (1,899-2,920). The median %dd-cfDNA for the C-CLAD (N=5) cohort was 1.79% (IQR: 1.04-2.29) and significantly elevated compared to the U-CLAD cohort (N=7, 0.49%; 0.28-0.88) (p=0.018). Absolute dd-cfDNA was also significantly higher in C-CLAD (43.2 cp/mL; 27.9-89.3) than the in U-CLAD cohort (19.6 cp/mL; 8.1-27.9) (p=0.048). Conclusions: We report a heretofore undescribed dichotomy of dd-cfDNA levels with CLAD ≥ 5-years, related specifically to elevation in allograft quantity as opposed to alteration in host plasma cfDNA. Further, dd-cfDNA analysis in association with co-morbid conditions in C-CLAD may offer insights for potential treatment and alleviation of molecular injury. Measurement of longitudinal absolute quantity dd-cfDNA may provide additional value for future clinical study design of pathobiology and CLAD treatment algorithms. |
| first_indexed | 2024-04-11T20:10:30Z |
| format | Article |
| id | doaj.art-89afa3fb30494295959ce02a31081ec2 |
| institution | Directory Open Access Journal |
| issn | 2451-9596 |
| language | English |
| last_indexed | 2024-04-11T20:10:30Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Transplantation Reports |
| spelling | doaj.art-89afa3fb30494295959ce02a31081ec22022-12-22T04:05:06ZengElsevierTransplantation Reports2451-95962022-09-0173100106Variability in plasma donor-derived cell-free DNA levels with CLAD more than 5-years after Lung Transplantation: Pilot dataDeborah Jo Levine0Zachary P. Demko1David J. Ross2Division of Pulmonary & Critical Care Medicine; University of Texas Health, San Antonio, United StatesMedical Affairs, Natera, Inc., San Carlos, California, United StatesMedical Affairs, Natera, Inc., San Carlos, California, United States; Corresponding author.Background: Chronic lung allograft dysfunction (CLAD) is a highly prevalent and devastating complication in lung transplant (LT), culminating in increased allograft failure, morbidity, and mortality. Determination of the fraction of plasma donor-derived cell-free DNA (dd-cfDNA) has emerged as a valuable noninvasive monitoring tool after LT; however, the increased variance of host cfDNA caused by infection and other inflammation can complicate the approach. Methods: In a retrospective pilot study, we analyzed both the fraction of dd-cfDNA (%dd-cfDNA) and absolute quantity of dd-cfDNA (cp/mL) in recipients with CLAD ≥ 5-year post-LT with co-morbid conditions (gastro-esophageal reflux, antibody-mediated rejection, or chronic infection) designated as complicated (C-CLAD) and uncomplicated (U-CLAD) cohorts. Results: Median time post-LT was 2,149 days (1,899-2,920). The median %dd-cfDNA for the C-CLAD (N=5) cohort was 1.79% (IQR: 1.04-2.29) and significantly elevated compared to the U-CLAD cohort (N=7, 0.49%; 0.28-0.88) (p=0.018). Absolute dd-cfDNA was also significantly higher in C-CLAD (43.2 cp/mL; 27.9-89.3) than the in U-CLAD cohort (19.6 cp/mL; 8.1-27.9) (p=0.048). Conclusions: We report a heretofore undescribed dichotomy of dd-cfDNA levels with CLAD ≥ 5-years, related specifically to elevation in allograft quantity as opposed to alteration in host plasma cfDNA. Further, dd-cfDNA analysis in association with co-morbid conditions in C-CLAD may offer insights for potential treatment and alleviation of molecular injury. Measurement of longitudinal absolute quantity dd-cfDNA may provide additional value for future clinical study design of pathobiology and CLAD treatment algorithms.http://www.sciencedirect.com/science/article/pii/S2451959622000142Cell-free DNACLADLung transplantBiomarker |
| spellingShingle | Deborah Jo Levine Zachary P. Demko David J. Ross Variability in plasma donor-derived cell-free DNA levels with CLAD more than 5-years after Lung Transplantation: Pilot data Transplantation Reports Cell-free DNA CLAD Lung transplant Biomarker |
| title | Variability in plasma donor-derived cell-free DNA levels with CLAD more than 5-years after Lung Transplantation: Pilot data |
| title_full | Variability in plasma donor-derived cell-free DNA levels with CLAD more than 5-years after Lung Transplantation: Pilot data |
| title_fullStr | Variability in plasma donor-derived cell-free DNA levels with CLAD more than 5-years after Lung Transplantation: Pilot data |
| title_full_unstemmed | Variability in plasma donor-derived cell-free DNA levels with CLAD more than 5-years after Lung Transplantation: Pilot data |
| title_short | Variability in plasma donor-derived cell-free DNA levels with CLAD more than 5-years after Lung Transplantation: Pilot data |
| title_sort | variability in plasma donor derived cell free dna levels with clad more than 5 years after lung transplantation pilot data |
| topic | Cell-free DNA CLAD Lung transplant Biomarker |
| url | http://www.sciencedirect.com/science/article/pii/S2451959622000142 |
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