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:	Thomas Drasch, Christian Bach, Markus Luber, Bernd Spriewald, Kirsten Utpatel, Maike Büttner-Herold, Bernhard Banas, Daniel Zecher
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	kidney transplantation donor-specific anti HLA antibodies sCD30 risk stratification ABMR antibody-mediated rejection Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/6777b0a68ea045898933956d874c2fa9
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spelling	oai:doaj.org-article:6777b0a68ea045898933956d874c2fa92021-11-08T05:58:40ZIncreased Levels of sCD30 Have No Impact on the Incidence of Early ABMR and Long-Term Outcome in Intermediate-Risk Renal Transplant Patients With Preformed DSA2296-858X10.3389/fmed.2021.778864https://doaj.org/article/6777b0a68ea045898933956d874c2fa92021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmed.2021.778864/fullhttps://doaj.org/toc/2296-858XBackground: 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.Thomas DraschChristian BachChristian BachMarkus LuberMarkus LuberBernd SpriewaldKirsten UtpatelMaike Büttner-HeroldBernhard BanasDaniel ZecherFrontiers Media S.A.articlekidney transplantationdonor-specific anti HLA antibodiessCD30risk stratificationABMRantibody-mediated rejectionMedicine (General)R5-920ENFrontiers in Medicine, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	kidney transplantation donor-specific anti HLA antibodies sCD30 risk stratification ABMR antibody-mediated rejection Medicine (General) R5-920
spellingShingle	kidney transplantation donor-specific anti HLA antibodies sCD30 risk stratification ABMR antibody-mediated rejection Medicine (General) R5-920 Thomas Drasch Christian Bach Christian Bach Markus Luber Markus Luber Bernd Spriewald Kirsten Utpatel Maike Büttner-Herold Bernhard Banas Daniel Zecher 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
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.
format	article
author	Thomas Drasch Christian Bach Christian Bach Markus Luber Markus Luber Bernd Spriewald Kirsten Utpatel Maike Büttner-Herold Bernhard Banas Daniel Zecher
author_facet	Thomas Drasch Christian Bach Christian Bach Markus Luber Markus Luber Bernd Spriewald Kirsten Utpatel Maike Büttner-Herold Bernhard Banas Daniel Zecher
author_sort	Thomas Drasch
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_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_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_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
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6777b0a68ea045898933956d874c2fa9
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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

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