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Verfasst von:Kim, Jon Jin [VerfasserIn]   i
 Fichtner, Alexander [VerfasserIn]   i
 Copley, Hannah C. [VerfasserIn]   i
 Gragert, Loren [VerfasserIn]   i
 Süsal, Caner [VerfasserIn]   i
 Dello Strologo, Luca [VerfasserIn]   i
 Oh, Jun [VerfasserIn]   i
 Pape, Lars [VerfasserIn]   i
 Weber, Lutz T. [VerfasserIn]   i
 Weitz, Marcus [VerfasserIn]   i
 König, Jens [VerfasserIn]   i
 Krupka, Kai [VerfasserIn]   i
 Tönshoff, Burkhard [VerfasserIn]   i
 Kosmoliaptsis, Vasilis [VerfasserIn]   i
Titel:Molecular HLA mismatching for prediction of primary humoral alloimmunity and graft function deterioration in paediatric kidney transplantation
Verf.angabe:Jon Jin Kim, Alexander Fichtner, Hannah C. Copley, Loren Gragert, Caner Süsal, Luca Dello Strologo, Jun Oh, Lars Pape, Lutz T. Weber, Marcus Weitz, Jens König, Kai Krupka, Burkhard Tönshoff and Vasilis Kosmoliaptsis
E-Jahr:2023
Jahr:15 March 2023
Umfang:14 S.
Fussnoten:Gesehen am 23.05.2023
Titel Quelle:Enthalten in: Frontiers in immunology
Ort Quelle:Lausanne : Frontiers Media, 2010
Jahr Quelle:2023
Band/Heft Quelle:14(2023) vom: März, Artikel-ID 1092335, Seite 1-14
ISSN Quelle:1664-3224
Abstract:IntroductionRejection remains the main cause of allograft failure in paediatric kidney transplantation and is driven by donor-recipient HLA mismatching. Modern computational algorithms enable assessment of HLA mismatch immunogenicity at the molecular level (molecular-mismatch, molMM). Whilst molMM has been shown to correlate with alloimmune outcomes, evidence demonstrating improved prediction performance against traditional antigen mismatching (antMM) is lacking.MethodsWe analysed 177 patients from the CERTAIN registry (median follow-up 4.5 years). molMM scores included Amino-Acid-Mismatch-Score (AAMS), Electrostatic-Mismatch-Score (EMS3D) and netMHCIIpan (netMHC1k: peptide binding affinity ≤1000 nM; netMHC: binding affinity ≤500 nM plus rank <2%). We stratified patients into high/low-risk groups based on risk models of DSA development.ResultsDonor-specific HLA antibodies (DSA) predominantly targeted the highest scoring molMM donor antigen within each HLA locus. MolMM scores offered superior discrimination versus antMM in predicting de novo DSA for all HLA loci; the EMS3D algorithm had particularly consistent performance (area under the receiver operating characteristic curve (AUC) >0.7 for all HLA loci vs. 0.52-0.70 for antMM). ABMR (but not TCMR) was associated with HLA-DQ molMM scores (AAMS, EMS3D and netMHC). Patients with high-risk HLA-DQ molMM had increased risk of graft function deterioration (50% reduction in baseline eGFR (eGFR50), adjusted HR: 3.5, 95% CI 1.6-8.2 high vs. low EMS3D). Multivariable modelling of the eGFR50 outcome using EMS3D HLA-DQ stratification showed better discrimination (AUC EMS3D vs. antMM at 2 years: 0.81 vs. 0.77, at 4.5 years: 0.72 vs. 0.64) and stratified more patients into the low-risk group, compared to traditional antMM.ConclusionMolecular mismatching was superior to antigen mismatching in predicting humoral alloimmunity. Molecular HLA-DQ mismatching appears to be a significant prognostic factor for graft function deterioration in paediatric kidney transplantation.
DOI:doi:10.3389/fimmu.2023.1092335
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

kostenfrei: Volltext: https://doi.org/10.3389/fimmu.2023.1092335
 Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1092335
 DOI: https://doi.org/10.3389/fimmu.2023.1092335
Datenträger:Online-Ressource
Sprache:eng
Bibliogr. Hinweis:Ergänzung: Kim, Jon Jin: Corrigendum: Molecular HLA mismatching for prediction of primary humoral alloimmunity and graft function deterioration in paediatric kidney transplantation
K10plus-PPN:1845965205
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