Evaluation of de novo donor specific antibodies after kidney transplantation in the era of donor-derived cell-free DNA
BackgroundDonor-derived cell-free DNA (dd-cfDNA) is a promising non-invasive biomarker for detecting graft injury in solid organ transplant recipients. Elevated dd-cfDNA levels are strongly associated with rejection and graft injury, especially antibody-mediated rejection (ABMR). While de novo donor...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1530065/full |
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| author | Yuan Tian Lukas Frischknecht Anna Mallone Fabian Rössler Thomas Schachtner Jakob Nilsson |
| author_facet | Yuan Tian Lukas Frischknecht Anna Mallone Fabian Rössler Thomas Schachtner Jakob Nilsson |
| author_sort | Yuan Tian |
| collection | DOAJ |
| description | BackgroundDonor-derived cell-free DNA (dd-cfDNA) is a promising non-invasive biomarker for detecting graft injury in solid organ transplant recipients. Elevated dd-cfDNA levels are strongly associated with rejection and graft injury, especially antibody-mediated rejection (ABMR). While de novo donor-specific antibodies (dnDSA) are crucial in ABMR, the relationship between dd-cfDNA levels and dnDSA features, such as DSA category, MFI and HLA target loci, remains unclear.MethodsWe analyzed dd-cfDNA levels in 75 kidney transplant recipients who developed dnDSA post-transplant. dnDSA were categorized as “true”, “possible”, or “false” based on bead reactivity patterns and HLA typing. dd-cfDNA was assessed alongside dnDSA detection and sequential follow-up samples in a subgroup.Results“True” dnDSA showed significantly higher dd-cfDNA levels compared to “possible” and “false” groups. None of the dd-cfDNA values in the “false” group exceeded 0.6%, and only a small fraction of the “possible” group had values slightly above 0.6%. dd-cfDNA levels were not significantly affected by dnDSA target loci or number. A strong correlation between cumulative dnDSA MFI and dd-cfDNA levels was observed, especially in patients with “true” HLA-DQ-directed dnDSA. Sequential dd-cfDNA analysis showed dynamic changes in 25% of patients, all from the “true” dnDSA group, which tended to align with shifts in cumulative MFI over time.ConclusionThese findings highlight the correlation between cumulative dnDSA MFI and dd-cfDNA levels, particularly in HLA-DQ-directed dnDSA, and suggest graft injury is dynamic in dnDSA-positive patients. Integrated monitoring of dnDSA and dd-cfDNA offers a promising non-invasive approach for assessing graft injury and alloimmunity, potentially enhancing post-transplant care. |
| format | Article |
| id | doaj-art-7afbc8e579cd4218bf4daed6bb3d0351 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-7afbc8e579cd4218bf4daed6bb3d03512025-01-16T05:10:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15300651530065Evaluation of de novo donor specific antibodies after kidney transplantation in the era of donor-derived cell-free DNAYuan Tian0Lukas Frischknecht1Anna Mallone2Fabian Rössler3Thomas Schachtner4Jakob Nilsson5Department of Immunology, University Hospital Zurich (USZ), Zurich, SwitzerlandDepartment of Immunology, University Hospital Zurich (USZ), Zurich, SwitzerlandDepartment of Immunology, University Hospital Zurich (USZ), Zurich, SwitzerlandDepartment of Surgery and Transplantation, University Hospital Zurich, Zurich, SwitzerlandDivision of Nephrology, University Hospital Zurich, Zurich, SwitzerlandDepartment of Immunology, University Hospital Zurich (USZ), Zurich, SwitzerlandBackgroundDonor-derived cell-free DNA (dd-cfDNA) is a promising non-invasive biomarker for detecting graft injury in solid organ transplant recipients. Elevated dd-cfDNA levels are strongly associated with rejection and graft injury, especially antibody-mediated rejection (ABMR). While de novo donor-specific antibodies (dnDSA) are crucial in ABMR, the relationship between dd-cfDNA levels and dnDSA features, such as DSA category, MFI and HLA target loci, remains unclear.MethodsWe analyzed dd-cfDNA levels in 75 kidney transplant recipients who developed dnDSA post-transplant. dnDSA were categorized as “true”, “possible”, or “false” based on bead reactivity patterns and HLA typing. dd-cfDNA was assessed alongside dnDSA detection and sequential follow-up samples in a subgroup.Results“True” dnDSA showed significantly higher dd-cfDNA levels compared to “possible” and “false” groups. None of the dd-cfDNA values in the “false” group exceeded 0.6%, and only a small fraction of the “possible” group had values slightly above 0.6%. dd-cfDNA levels were not significantly affected by dnDSA target loci or number. A strong correlation between cumulative dnDSA MFI and dd-cfDNA levels was observed, especially in patients with “true” HLA-DQ-directed dnDSA. Sequential dd-cfDNA analysis showed dynamic changes in 25% of patients, all from the “true” dnDSA group, which tended to align with shifts in cumulative MFI over time.ConclusionThese findings highlight the correlation between cumulative dnDSA MFI and dd-cfDNA levels, particularly in HLA-DQ-directed dnDSA, and suggest graft injury is dynamic in dnDSA-positive patients. Integrated monitoring of dnDSA and dd-cfDNA offers a promising non-invasive approach for assessing graft injury and alloimmunity, potentially enhancing post-transplant care.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1530065/fullkidney transplantationDd-cfDNAdonor specific antibodiesDSAmean fluorescence intensityMFI |
| spellingShingle | Yuan Tian Lukas Frischknecht Anna Mallone Fabian Rössler Thomas Schachtner Jakob Nilsson Evaluation of de novo donor specific antibodies after kidney transplantation in the era of donor-derived cell-free DNA Frontiers in Immunology kidney transplantation Dd-cfDNA donor specific antibodies DSA mean fluorescence intensity MFI |
| title | Evaluation of de novo donor specific antibodies after kidney transplantation in the era of donor-derived cell-free DNA |
| title_full | Evaluation of de novo donor specific antibodies after kidney transplantation in the era of donor-derived cell-free DNA |
| title_fullStr | Evaluation of de novo donor specific antibodies after kidney transplantation in the era of donor-derived cell-free DNA |
| title_full_unstemmed | Evaluation of de novo donor specific antibodies after kidney transplantation in the era of donor-derived cell-free DNA |
| title_short | Evaluation of de novo donor specific antibodies after kidney transplantation in the era of donor-derived cell-free DNA |
| title_sort | evaluation of de novo donor specific antibodies after kidney transplantation in the era of donor derived cell free dna |
| topic | kidney transplantation Dd-cfDNA donor specific antibodies DSA mean fluorescence intensity MFI |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1530065/full |
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