De Novo donor-specific anti-HLA antibody risk stratification in kidney transplantation using a combination of B cell and T cell molecular mismatch assessment

De Novo donor-specific anti-HLA antibody risk stratification in kidney transplantation using a combination of B cell and T cell molecular mismatch assessment

IntroductionThe presence of de novo donor-specific antibody (dnDSA) has detrimental effect on allograft outcomes in kidney transplantation. As humoral responses in transplantation are elicited targeting non-self-epitopes on donor HLA proteins, assessing HLA mismatches at the molecular level provides...

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Bibliographic Details
Main Authors: Elaine Chou-Wu, Matthias Niemann, Danny Youngs, Idoia Gimferrer
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Immunology
Subjects:
HLA molecular mismatch
major histocompatibility complex (MHC)
risk stratification
kidney transplantation
de novo DSA
Snow
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1508796/full
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Summary:IntroductionThe presence of de novo donor-specific antibody (dnDSA) has detrimental effect on allograft outcomes in kidney transplantation. As humoral responses in transplantation are elicited targeting non-self-epitopes on donor HLA proteins, assessing HLA mismatches at the molecular level provides a refined means for immunological risk stratification.MethodsIn the present study, we utilized three HLA molecular mismatch assessment algorithms, Snow, HLAMatchmaker, and PIRCHE-II, to evaluate the independent and synergistic association of B cell and T cell epitope mismatches with dnDSA development in a cohort of 843 kidney transplant recipients.ResultsOur results demonstrated that B cell and T cell epitope mismatches at HLA Class I and DRB1/DQB1 loci are remarkably increased in dnDSA-positive recipients, even after normalization by allele mismatch numbers in individual study subjects. Furthermore, elevated Snow, verified eplet mismatches, and PIRCHE-II scores are significantly associated with dnDSA occurrence individually and in combination.ConclusionOur findings highlight the value of utilizing B cell and T cell epitope mismatch evaluation in living donor selection and immunological risk stratification to improve transplant outcomes.
ISSN:1664-3224

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