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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1508796/full |
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| author | Elaine Chou-Wu Matthias Niemann Danny Youngs Idoia Gimferrer |
| author_facet | Elaine Chou-Wu Matthias Niemann Danny Youngs Idoia Gimferrer |
| author_sort | Elaine Chou-Wu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a7c96915c11c4e1bac3827cf392cda6f |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-a7c96915c11c4e1bac3827cf392cda6f2025-08-20T03:11:17ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15087961508796De Novo donor-specific anti-HLA antibody risk stratification in kidney transplantation using a combination of B cell and T cell molecular mismatch assessmentElaine Chou-Wu0Matthias Niemann1Danny Youngs2Idoia Gimferrer3Immunogenetics/HLA Laboratory, Bloodworks Northwest, Seattle, WA, United StatesPIRCHE AG, Berlin, GermanyImmunogenetics/HLA Laboratory, Bloodworks Northwest, Seattle, WA, United StatesImmunogenetics/HLA Laboratory, Bloodworks Northwest, Seattle, WA, United StatesIntroductionThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1508796/fullHLA molecular mismatchmajor histocompatibility complex (MHC)risk stratificationkidney transplantationde novo DSASnow |
| spellingShingle | Elaine Chou-Wu Matthias Niemann Danny Youngs Idoia Gimferrer De Novo donor-specific anti-HLA antibody risk stratification in kidney transplantation using a combination of B cell and T cell molecular mismatch assessment Frontiers in Immunology HLA molecular mismatch major histocompatibility complex (MHC) risk stratification kidney transplantation de novo DSA Snow |
| title | De Novo donor-specific anti-HLA antibody risk stratification in kidney transplantation using a combination of B cell and T cell molecular mismatch assessment |
| title_full | De Novo donor-specific anti-HLA antibody risk stratification in kidney transplantation using a combination of B cell and T cell molecular mismatch assessment |
| title_fullStr | De Novo donor-specific anti-HLA antibody risk stratification in kidney transplantation using a combination of B cell and T cell molecular mismatch assessment |
| title_full_unstemmed | De Novo donor-specific anti-HLA antibody risk stratification in kidney transplantation using a combination of B cell and T cell molecular mismatch assessment |
| title_short | De Novo donor-specific anti-HLA antibody risk stratification in kidney transplantation using a combination of B cell and T cell molecular mismatch assessment |
| title_sort | de novo donor specific anti hla antibody risk stratification in kidney transplantation using a combination of b cell and t cell molecular mismatch assessment |
| topic | HLA molecular mismatch major histocompatibility complex (MHC) risk stratification kidney transplantation de novo DSA Snow |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1508796/full |
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