Detection of donor-derived cell-free DNA in the setting of multiple kidney transplantations
Copyright © 2024 Pettersson, Frischknecht, Westerling, Ramezanali, Weidmann, Lopez, Schachtner and Nilsson..
Background: The routine use of donor-derived cell-free DNA (dd-cfDNA) assays to monitor graft damage in patients after kidney transplantation is being implemented in many transplant centers worldwide. The interpretation of the results can be complicated in the setting of multiple sequential kidney transplantations where accurate donor assignment of the detected dd-cfDNA can be methodologically challenging.
Methods: We investigated the ability of a new next-generation sequencing (NGS)-based dd-cfDNA assay to accurately identify the source of the detected dd-cfDNA in artificially generated samples as well as clinical samples from 31 patients who had undergone two sequential kidney transplantations.
Results: The assay showed a high accuracy in quantifying and correctly assigning dd-cfDNA in our artificially generated chimeric sample experiments over a clinically meaningful quantitative range. In our clinical samples, we were able to detect dd-cfDNA from the first transplanted (nonfunctioning) graft in 20% of the analyzed patients. The amount of dd-cfDNA detected from the first graft was consistently in the range of 0.1%-0.6% and showed a fluctuation over time in patients where we analyzed sequential samples.
Conclusion: This is the first report on the use of a dd-cfDNA assay to detect dd-cfDNA from multiple kidney transplants. Our data show that a clinically relevant fraction of the transplanted patients have detectable dd-cfDNA from the first donor graft and that the amount of detected dd-cfDNA is in a range where it could influence clinical decision-making.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Frontiers in immunology - 15(2024) vom: 26., Seite 1282521 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Pettersson, Linnea [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
ABMR |
|---|
| Anmerkungen: |
Date Completed 11.03.2024 Date Revised 26.03.2024 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.3389/fimmu.2024.1282521 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369447824 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369447824 | ||
| 003 | DE-627 | ||
| 005 | 20240328000053.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240308s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3389/fimmu.2024.1282521 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1351.xml |
| 035 | |a (DE-627)NLM369447824 | ||
| 035 | |a (NLM)38455037 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Pettersson, Linnea |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Detection of donor-derived cell-free DNA in the setting of multiple kidney transplantations |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 11.03.2024 | ||
| 500 | |a Date Revised 26.03.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Pettersson, Frischknecht, Westerling, Ramezanali, Weidmann, Lopez, Schachtner and Nilsson. | ||
| 520 | |a Background: The routine use of donor-derived cell-free DNA (dd-cfDNA) assays to monitor graft damage in patients after kidney transplantation is being implemented in many transplant centers worldwide. The interpretation of the results can be complicated in the setting of multiple sequential kidney transplantations where accurate donor assignment of the detected dd-cfDNA can be methodologically challenging | ||
| 520 | |a Methods: We investigated the ability of a new next-generation sequencing (NGS)-based dd-cfDNA assay to accurately identify the source of the detected dd-cfDNA in artificially generated samples as well as clinical samples from 31 patients who had undergone two sequential kidney transplantations | ||
| 520 | |a Results: The assay showed a high accuracy in quantifying and correctly assigning dd-cfDNA in our artificially generated chimeric sample experiments over a clinically meaningful quantitative range. In our clinical samples, we were able to detect dd-cfDNA from the first transplanted (nonfunctioning) graft in 20% of the analyzed patients. The amount of dd-cfDNA detected from the first graft was consistently in the range of 0.1%-0.6% and showed a fluctuation over time in patients where we analyzed sequential samples | ||
| 520 | |a Conclusion: This is the first report on the use of a dd-cfDNA assay to detect dd-cfDNA from multiple kidney transplants. Our data show that a clinically relevant fraction of the transplanted patients have detectable dd-cfDNA from the first donor graft and that the amount of detected dd-cfDNA is in a range where it could influence clinical decision-making | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a ABMR | |
| 650 | 4 | |a Dd-cfDNA | |
| 650 | 4 | |a NGS | |
| 650 | 4 | |a donor derived cell free DNA | |
| 650 | 4 | |a graft loss | |
| 650 | 4 | |a kidney transplantation | |
| 650 | 4 | |a second kidney transplantation | |
| 650 | 7 | |a Cell-Free Nucleic Acids |2 NLM | |
| 700 | 1 | |a Frischknecht, Lukas |e verfasserin |4 aut | |
| 700 | 1 | |a Westerling, Sofia |e verfasserin |4 aut | |
| 700 | 1 | |a Ramezanali, Hamid |e verfasserin |4 aut | |
| 700 | 1 | |a Weidmann, Lukas |e verfasserin |4 aut | |
| 700 | 1 | |a Lopez, Kai Castrezana |e verfasserin |4 aut | |
| 700 | 1 | |a Schachtner, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Nilsson, Jakob |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Frontiers in immunology |d 2010 |g 15(2024) vom: 26., Seite 1282521 |w (DE-627)NLM215811453 |x 1664-3224 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2024 |g day:26 |g pages:1282521 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3389/fimmu.2024.1282521 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2024 |b 26 |h 1282521 | ||