Assessing the Predictive Power of PIRCHE-II Scores for the Development of De Novo Donor-Specific Antibodies After Simultaneous Pancreas-Kidney Transplantation

The molecular HLA epitope mismatch is an advanced measure for developing de novo donor-specific antibodies (dnDSA) after kidney transplantation. Its relevance in simultaneous pancreas/kidney transplant recipients (SPKTRs) remains unclear. We investigated dnDSA development in 72 SPKTRs and 383 kidney...

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Main Authors: Francesca Raineri, Lukas Frischknecht, Jakob Nilsson, Fabian Rössler, Claudia Cavelti-Weder, Seraina von Moos, Thomas Schachtner
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Transplant International
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Online Access:https://www.frontierspartnerships.org/articles/10.3389/ti.2024.13720/full
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author Francesca Raineri
Lukas Frischknecht
Jakob Nilsson
Fabian Rössler
Claudia Cavelti-Weder
Seraina von Moos
Seraina von Moos
Thomas Schachtner
author_facet Francesca Raineri
Lukas Frischknecht
Jakob Nilsson
Fabian Rössler
Claudia Cavelti-Weder
Seraina von Moos
Seraina von Moos
Thomas Schachtner
author_sort Francesca Raineri
collection DOAJ
description The molecular HLA epitope mismatch is an advanced measure for developing de novo donor-specific antibodies (dnDSA) after kidney transplantation. Its relevance in simultaneous pancreas/kidney transplant recipients (SPKTRs) remains unclear. We investigated dnDSA development in 72 SPKTRs and 383 kidney transplant recipients (KTRs) and used the Predicted Indirectly Recognizable HLA-Epitopes (PIRCHE-II) algorithm to calculate the mismatch load of HLA-derived epitopes in total, per HLA-class, and per HLA-locus. At 1 year post-transplant, SPKTRs exhibited an increased dnDSA incidence (11.2% vs. 3.1%, p = 0.011); but not at 10 years post-transplant. In SPKTRs, preformed DSA (HR 2.872, p = 0.039) and younger donor age (HR 0.943, p = 0.017) were independent risk factors for developing dnDSA. PIRCHE-II scores for HLA-DQ correlated with dnDSA development upon univariate analysis (p = 0.044). Among 455 KTRs/SPKTRs, multivariate analysis identified PIRCHE-II scores for HLA-DQ (HR 1.023, p = 0.025) and ciclosporine use (HR 2.440, p = 0.001) as independent predictors of dnDSA development. Simultaneous pancreas/kidney transplantation (SPK) was an independent risk factor in case of preformed DSA only (HR 2.782, p = 0.037). High PIRCHE-II scores for HLA-DQ are crucial for dnDSA development in both SPKTRs and KTRs. The lack of an independent association of total PIRCHE-II scores urges caution in implementing it in post-transplantation risk assessment.
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spelling doaj-art-96ae6df2627542728e9e5bccc0949a892024-12-18T04:11:48ZengFrontiers Media S.A.Transplant International1432-22772024-12-013710.3389/ti.2024.1372013720Assessing the Predictive Power of PIRCHE-II Scores for the Development of De Novo Donor-Specific Antibodies After Simultaneous Pancreas-Kidney TransplantationFrancesca Raineri0Lukas Frischknecht1Jakob Nilsson2Fabian Rössler3Claudia Cavelti-Weder4Seraina von Moos5Seraina von Moos6Thomas Schachtner7Department of Nephrology, University Hospital Zurich, Zurich, SwitzerlandDepartment of Immunology, University Hospital Zurich, Zurich, SwitzerlandDepartment of Immunology, University Hospital Zurich, Zurich, SwitzerlandDepartment of Surgery and Transplantation, University Hospital Zurich, Zurich, SwitzerlandDepartment of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich, Zurich, SwitzerlandDepartment of Nephrology, University Hospital Zurich, Zurich, SwitzerlandDepartment of Nephrology, Canton Hospital Luzern, Lucerne, SwitzerlandDepartment of Nephrology, University Hospital Zurich, Zurich, SwitzerlandThe molecular HLA epitope mismatch is an advanced measure for developing de novo donor-specific antibodies (dnDSA) after kidney transplantation. Its relevance in simultaneous pancreas/kidney transplant recipients (SPKTRs) remains unclear. We investigated dnDSA development in 72 SPKTRs and 383 kidney transplant recipients (KTRs) and used the Predicted Indirectly Recognizable HLA-Epitopes (PIRCHE-II) algorithm to calculate the mismatch load of HLA-derived epitopes in total, per HLA-class, and per HLA-locus. At 1 year post-transplant, SPKTRs exhibited an increased dnDSA incidence (11.2% vs. 3.1%, p = 0.011); but not at 10 years post-transplant. In SPKTRs, preformed DSA (HR 2.872, p = 0.039) and younger donor age (HR 0.943, p = 0.017) were independent risk factors for developing dnDSA. PIRCHE-II scores for HLA-DQ correlated with dnDSA development upon univariate analysis (p = 0.044). Among 455 KTRs/SPKTRs, multivariate analysis identified PIRCHE-II scores for HLA-DQ (HR 1.023, p = 0.025) and ciclosporine use (HR 2.440, p = 0.001) as independent predictors of dnDSA development. Simultaneous pancreas/kidney transplantation (SPK) was an independent risk factor in case of preformed DSA only (HR 2.782, p = 0.037). High PIRCHE-II scores for HLA-DQ are crucial for dnDSA development in both SPKTRs and KTRs. The lack of an independent association of total PIRCHE-II scores urges caution in implementing it in post-transplantation risk assessment.https://www.frontierspartnerships.org/articles/10.3389/ti.2024.13720/fullsimultaneous pancreas and kidney transplantpreformed DSAde novo DSAepitope matchingPIRCHE-II score
spellingShingle Francesca Raineri
Lukas Frischknecht
Jakob Nilsson
Fabian Rössler
Claudia Cavelti-Weder
Seraina von Moos
Seraina von Moos
Thomas Schachtner
Assessing the Predictive Power of PIRCHE-II Scores for the Development of De Novo Donor-Specific Antibodies After Simultaneous Pancreas-Kidney Transplantation
Transplant International
simultaneous pancreas and kidney transplant
preformed DSA
de novo DSA
epitope matching
PIRCHE-II score
title Assessing the Predictive Power of PIRCHE-II Scores for the Development of De Novo Donor-Specific Antibodies After Simultaneous Pancreas-Kidney Transplantation
title_full Assessing the Predictive Power of PIRCHE-II Scores for the Development of De Novo Donor-Specific Antibodies After Simultaneous Pancreas-Kidney Transplantation
title_fullStr Assessing the Predictive Power of PIRCHE-II Scores for the Development of De Novo Donor-Specific Antibodies After Simultaneous Pancreas-Kidney Transplantation
title_full_unstemmed Assessing the Predictive Power of PIRCHE-II Scores for the Development of De Novo Donor-Specific Antibodies After Simultaneous Pancreas-Kidney Transplantation
title_short Assessing the Predictive Power of PIRCHE-II Scores for the Development of De Novo Donor-Specific Antibodies After Simultaneous Pancreas-Kidney Transplantation
title_sort assessing the predictive power of pirche ii scores for the development of de novo donor specific antibodies after simultaneous pancreas kidney transplantation
topic simultaneous pancreas and kidney transplant
preformed DSA
de novo DSA
epitope matching
PIRCHE-II score
url https://www.frontierspartnerships.org/articles/10.3389/ti.2024.13720/full
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