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Increased Levels of sCD30 Have No Impact on the Incidence of Early ABMR and Long-Term Outcome in Intermediate-Risk Renal Transplant Patients With Preformed DSA

Background: It is still incompletely understood why some patients with preformed donor-specific anti-HLA antibodies (DSA) have reduced kidney allograft survival secondary to antibody-mediated rejection (ABMR), whereas many DSA-positive patients have favorable long-term outcomes. Elevated levels of s...

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Autores principales: Drasch, Thomas, Bach, Christian, Luber, Markus, Spriewald, Bernd, Utpatel, Kirsten, Büttner-Herold, Maike, Banas, Bernhard, Zecher, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606593/
https://www.ncbi.nlm.nih.gov/pubmed/34820407
http://dx.doi.org/10.3389/fmed.2021.778864
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author Drasch, Thomas
Bach, Christian
Luber, Markus
Spriewald, Bernd
Utpatel, Kirsten
Büttner-Herold, Maike
Banas, Bernhard
Zecher, Daniel
author_facet Drasch, Thomas
Bach, Christian
Luber, Markus
Spriewald, Bernd
Utpatel, Kirsten
Büttner-Herold, Maike
Banas, Bernhard
Zecher, Daniel
author_sort Drasch, Thomas
collection PubMed
description Background: It is still incompletely understood why some patients with preformed donor-specific anti-HLA antibodies (DSA) have reduced kidney allograft survival secondary to antibody-mediated rejection (ABMR), whereas many DSA-positive patients have favorable long-term outcomes. Elevated levels of soluble CD30 (sCD30) have emerged as a promising biomarker indicating deleterious T-cell help in conjunction with DSA in immunologically high-risk patients. We hypothesized that this would also be true in intermediate-risk patients. Methods: We retrospectively analyzed pre-transplant sera from 287 CDC-crossmatch negative patients treated with basiliximab induction and tacrolimus-based maintenance therapy for the presence of DSA and sCD30. The incidence of ABMR according to the Banff 2019 classification and death-censored allograft survival were determined. Results: During a median follow-up of 7.4 years, allograft survival was significantly lower in DSA-positive as compared to DSA-negative patients (p < 0.001). In DSA-positive patients, most pronounced in those with strong DSA (MFI > 5,000), increased levels of sCD30 were associated with accelerated graft loss compared to patients with low sCD30 (3-year allograft survival 75 vs. 95%). Long-term survival, however, was comparable in DSA-positive patients irrespective of sCD30 status. Likewise, the incidence of early ABMR and lesion score characteristics were comparable between sCD30-positive and sCD30-negative patients with DSA. Finally, increased sCD30 levels were not predictive for early persistence of DSA. Conclusion: Preformed DSA are associated with an increased risk for ABMR and long-term graft loss independent of sCD30 levels in intermediate-risk kidney transplant patients.
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spelling pubmed-86065932021-11-23 Increased Levels of sCD30 Have No Impact on the Incidence of Early ABMR and Long-Term Outcome in Intermediate-Risk Renal Transplant Patients With Preformed DSA Drasch, Thomas Bach, Christian Luber, Markus Spriewald, Bernd Utpatel, Kirsten Büttner-Herold, Maike Banas, Bernhard Zecher, Daniel Front Med (Lausanne) Medicine Background: It is still incompletely understood why some patients with preformed donor-specific anti-HLA antibodies (DSA) have reduced kidney allograft survival secondary to antibody-mediated rejection (ABMR), whereas many DSA-positive patients have favorable long-term outcomes. Elevated levels of soluble CD30 (sCD30) have emerged as a promising biomarker indicating deleterious T-cell help in conjunction with DSA in immunologically high-risk patients. We hypothesized that this would also be true in intermediate-risk patients. Methods: We retrospectively analyzed pre-transplant sera from 287 CDC-crossmatch negative patients treated with basiliximab induction and tacrolimus-based maintenance therapy for the presence of DSA and sCD30. The incidence of ABMR according to the Banff 2019 classification and death-censored allograft survival were determined. Results: During a median follow-up of 7.4 years, allograft survival was significantly lower in DSA-positive as compared to DSA-negative patients (p < 0.001). In DSA-positive patients, most pronounced in those with strong DSA (MFI > 5,000), increased levels of sCD30 were associated with accelerated graft loss compared to patients with low sCD30 (3-year allograft survival 75 vs. 95%). Long-term survival, however, was comparable in DSA-positive patients irrespective of sCD30 status. Likewise, the incidence of early ABMR and lesion score characteristics were comparable between sCD30-positive and sCD30-negative patients with DSA. Finally, increased sCD30 levels were not predictive for early persistence of DSA. Conclusion: Preformed DSA are associated with an increased risk for ABMR and long-term graft loss independent of sCD30 levels in intermediate-risk kidney transplant patients. Frontiers Media S.A. 2021-11-08 /pmc/articles/PMC8606593/ /pubmed/34820407 http://dx.doi.org/10.3389/fmed.2021.778864 Text en Copyright © 2021 Drasch, Bach, Luber, Spriewald, Utpatel, Büttner-Herold, Banas and Zecher. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Drasch, Thomas
Bach, Christian
Luber, Markus
Spriewald, Bernd
Utpatel, Kirsten
Büttner-Herold, Maike
Banas, Bernhard
Zecher, Daniel
Increased Levels of sCD30 Have No Impact on the Incidence of Early ABMR and Long-Term Outcome in Intermediate-Risk Renal Transplant Patients With Preformed DSA
title Increased Levels of sCD30 Have No Impact on the Incidence of Early ABMR and Long-Term Outcome in Intermediate-Risk Renal Transplant Patients With Preformed DSA
title_full Increased Levels of sCD30 Have No Impact on the Incidence of Early ABMR and Long-Term Outcome in Intermediate-Risk Renal Transplant Patients With Preformed DSA
title_fullStr Increased Levels of sCD30 Have No Impact on the Incidence of Early ABMR and Long-Term Outcome in Intermediate-Risk Renal Transplant Patients With Preformed DSA
title_full_unstemmed Increased Levels of sCD30 Have No Impact on the Incidence of Early ABMR and Long-Term Outcome in Intermediate-Risk Renal Transplant Patients With Preformed DSA
title_short Increased Levels of sCD30 Have No Impact on the Incidence of Early ABMR and Long-Term Outcome in Intermediate-Risk Renal Transplant Patients With Preformed DSA
title_sort increased levels of scd30 have no impact on the incidence of early abmr and long-term outcome in intermediate-risk renal transplant patients with preformed dsa
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606593/
https://www.ncbi.nlm.nih.gov/pubmed/34820407
http://dx.doi.org/10.3389/fmed.2021.778864
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