The detrimental effect of donor-specific antibodies is irrespective of its level in highly-immunized living donor kidney transplant recipients: A case-control series

T Tramper; D L Roelen; S H Brand-Schaaf; J A Kal-van Gestel; M M L Kho; M E J Reinders; J I Roodnat; J van de Wetering; M G H Betjes; A E de Weerd

doi:10.3389/fimmu.2022.1093359

The detrimental effect of donor-specific antibodies is irrespective of its level in highly-immunized living donor kidney transplant recipients: A case-control series

T Tramper, D L Roelen, S H Brand-Schaaf, J A Kal-van Gestel, M M L Kho, M E J Reinders, J I Roodnat, J van de Wetering, M G H Betjes, A E de Weerd

Internal Medicine

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Abstract

BACKGROUND: The impact of donor-specific antibodies (DSA) in (highly-) immunized living donor kidney transplant recipients is reported differentially in various patient cohorts.

METHODS: We have performed a retrospective analysis of all consecutive HLA-incompatible living donor kidney transplant recipients in our center between 2010-2019. Recipients who underwent plasmafiltration for a positive CDC-crossmatch were excluded. For each DSA+ recipient (DSA+), one immunized recipient without DSA (pPRA+) and two non-immunized recipients (pPRA-) were included. Patient and graft survival were analyzed and a subgroup analysis of DSA+ recipients was performed.

RESULTS: For 63 DSA+ recipients, 63 PRA+ and 126 PRA- recipients were included. 26 (41%) had class I, 24 (38%) class II and 13 (21%) combined HLA class I and II DSA. Death-censored graft survival was inferior in DSA+ recipients compared to pPRA+ (HR 2.38 [95% CI 1.00-5.70]) as well as to pPRA- (HR 3.91 [1.86-8.22]). In multivariate analysis, DSA remained of negative influence on death-censored graft survival. Flowcytometric crossmatch, MFI value, HLA class and origin of DSA were not of significant impact.

CONCLUSION: In our cohort of (highly-) immunized recipients, pretransplant DSA led to inferior death-censored graft survival. There were no "safe" DSA characteristics since only DSA per se impacted death-censored graft survival.

Original language	English
Article number	1093359
Journal	Frontiers in Immunology
Volume	13
DOIs	https://doi.org/10.3389/fimmu.2022.1093359
Publication status	Published - 10 Jan 2023

Bibliographical note

Funding Information:
Unrestricted or unconditional grant by HANSA Biopharma AB. Statement to contract number 001825. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.

Publisher Copyright:
Copyright © 2023 Tramper, Roelen, Brand-Schaaf, Kal-van Gestel, Kho, Reinders, Roodnat, van de Wetering, Betjes and de Weerd.

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10.3389/fimmu.2022.1093359Licence: CC BY

The detrimental effect of donor-specific antibodies is irrespective of its level in highly-immunized living donor kidney transplant recipientsFinal published version, 1.29 MBLicence: CC BY

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Tramper, T., Roelen, D. L., Brand-Schaaf, S. H., Kal-van Gestel, J. A., Kho, M. M. L., Reinders, M. E. J., Roodnat, J. I., van de Wetering, J., Betjes, M. G. H., & de Weerd, A. E. (2023). The detrimental effect of donor-specific antibodies is irrespective of its level in highly-immunized living donor kidney transplant recipients: A case-control series. Frontiers in Immunology, 13, Article 1093359. https://doi.org/10.3389/fimmu.2022.1093359

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title = "The detrimental effect of donor-specific antibodies is irrespective of its level in highly-immunized living donor kidney transplant recipients: A case-control series",

abstract = "BACKGROUND: The impact of donor-specific antibodies (DSA) in (highly-) immunized living donor kidney transplant recipients is reported differentially in various patient cohorts.METHODS: We have performed a retrospective analysis of all consecutive HLA-incompatible living donor kidney transplant recipients in our center between 2010-2019. Recipients who underwent plasmafiltration for a positive CDC-crossmatch were excluded. For each DSA+ recipient (DSA+), one immunized recipient without DSA (pPRA+) and two non-immunized recipients (pPRA-) were included. Patient and graft survival were analyzed and a subgroup analysis of DSA+ recipients was performed.RESULTS: For 63 DSA+ recipients, 63 PRA+ and 126 PRA- recipients were included. 26 (41\%) had class I, 24 (38\%) class II and 13 (21\%) combined HLA class I and II DSA. Death-censored graft survival was inferior in DSA+ recipients compared to pPRA+ (HR 2.38 [95\% CI 1.00-5.70]) as well as to pPRA- (HR 3.91 [1.86-8.22]). In multivariate analysis, DSA remained of negative influence on death-censored graft survival. Flowcytometric crossmatch, MFI value, HLA class and origin of DSA were not of significant impact.CONCLUSION: In our cohort of (highly-) immunized recipients, pretransplant DSA led to inferior death-censored graft survival. There were no {"}safe{"} DSA characteristics since only DSA per se impacted death-censored graft survival.",

author = "T Tramper and Roelen, \{D L\} and Brand-Schaaf, \{S H\} and \{Kal-van Gestel\}, \{J A\} and Kho, \{M M L\} and Reinders, \{M E J\} and Roodnat, \{J I\} and \{van de Wetering\}, J and Betjes, \{M G H\} and \{de Weerd\}, \{A E\}",

note = "Funding Information: Unrestricted or unconditional grant by HANSA Biopharma AB. Statement to contract number 001825. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. Publisher Copyright: Copyright {\textcopyright} 2023 Tramper, Roelen, Brand-Schaaf, Kal-van Gestel, Kho, Reinders, Roodnat, van de Wetering, Betjes and de Weerd.",

year = "2023",

month = jan,

day = "10",

doi = "10.3389/fimmu.2022.1093359",

language = "English",

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journal = "Frontiers in Immunology",

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Tramper, T, Roelen, DL, Brand-Schaaf, SH, Kal-van Gestel, JA , Kho, MML, Reinders, MEJ, Roodnat, JI , van de Wetering, J , Betjes, MGH & de Weerd, AE 2023, 'The detrimental effect of donor-specific antibodies is irrespective of its level in highly-immunized living donor kidney transplant recipients: A case-control series', Frontiers in Immunology, vol. 13, 1093359. https://doi.org/10.3389/fimmu.2022.1093359

TY - JOUR

T1 - The detrimental effect of donor-specific antibodies is irrespective of its level in highly-immunized living donor kidney transplant recipients

T2 - A case-control series

AU - Tramper, T

AU - Roelen, D L

AU - Brand-Schaaf, S H

AU - Kal-van Gestel, J A

AU - Kho, M M L

AU - Reinders, M E J

AU - Roodnat, J I

AU - van de Wetering, J

AU - Betjes, M G H

AU - de Weerd, A E

N1 - Funding Information: Unrestricted or unconditional grant by HANSA Biopharma AB. Statement to contract number 001825. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. Publisher Copyright: Copyright © 2023 Tramper, Roelen, Brand-Schaaf, Kal-van Gestel, Kho, Reinders, Roodnat, van de Wetering, Betjes and de Weerd.

PY - 2023/1/10

Y1 - 2023/1/10

N2 - BACKGROUND: The impact of donor-specific antibodies (DSA) in (highly-) immunized living donor kidney transplant recipients is reported differentially in various patient cohorts.METHODS: We have performed a retrospective analysis of all consecutive HLA-incompatible living donor kidney transplant recipients in our center between 2010-2019. Recipients who underwent plasmafiltration for a positive CDC-crossmatch were excluded. For each DSA+ recipient (DSA+), one immunized recipient without DSA (pPRA+) and two non-immunized recipients (pPRA-) were included. Patient and graft survival were analyzed and a subgroup analysis of DSA+ recipients was performed.RESULTS: For 63 DSA+ recipients, 63 PRA+ and 126 PRA- recipients were included. 26 (41%) had class I, 24 (38%) class II and 13 (21%) combined HLA class I and II DSA. Death-censored graft survival was inferior in DSA+ recipients compared to pPRA+ (HR 2.38 [95% CI 1.00-5.70]) as well as to pPRA- (HR 3.91 [1.86-8.22]). In multivariate analysis, DSA remained of negative influence on death-censored graft survival. Flowcytometric crossmatch, MFI value, HLA class and origin of DSA were not of significant impact.CONCLUSION: In our cohort of (highly-) immunized recipients, pretransplant DSA led to inferior death-censored graft survival. There were no "safe" DSA characteristics since only DSA per se impacted death-censored graft survival.

AB - BACKGROUND: The impact of donor-specific antibodies (DSA) in (highly-) immunized living donor kidney transplant recipients is reported differentially in various patient cohorts.METHODS: We have performed a retrospective analysis of all consecutive HLA-incompatible living donor kidney transplant recipients in our center between 2010-2019. Recipients who underwent plasmafiltration for a positive CDC-crossmatch were excluded. For each DSA+ recipient (DSA+), one immunized recipient without DSA (pPRA+) and two non-immunized recipients (pPRA-) were included. Patient and graft survival were analyzed and a subgroup analysis of DSA+ recipients was performed.RESULTS: For 63 DSA+ recipients, 63 PRA+ and 126 PRA- recipients were included. 26 (41%) had class I, 24 (38%) class II and 13 (21%) combined HLA class I and II DSA. Death-censored graft survival was inferior in DSA+ recipients compared to pPRA+ (HR 2.38 [95% CI 1.00-5.70]) as well as to pPRA- (HR 3.91 [1.86-8.22]). In multivariate analysis, DSA remained of negative influence on death-censored graft survival. Flowcytometric crossmatch, MFI value, HLA class and origin of DSA were not of significant impact.CONCLUSION: In our cohort of (highly-) immunized recipients, pretransplant DSA led to inferior death-censored graft survival. There were no "safe" DSA characteristics since only DSA per se impacted death-censored graft survival.

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U2 - 10.3389/fimmu.2022.1093359

DO - 10.3389/fimmu.2022.1093359

M3 - Article

C2 - 36703958

SN - 1664-3224

VL - 13

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 1093359

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The detrimental effect of donor-specific antibodies is irrespective of its level in highly-immunized living donor kidney transplant recipients: A case-control series

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