Molecular HLA mismatching for prediction of primary humoral alloimmunity and graft function deterioration in paediatric kidney transplantation

Autor:	Kim, Jon Jin, Fichtner, Alexander, Copley, Hannah C, Gragert, Loren, Süsal, Caner, Dello Strologo, Luca, Oh, Jun, Pape, Lars, Weber, Lutz T, Weitz, Marcus, König, Jens, Krupka, Kai, Tönshoff, Burkhard, Kosmoliaptsis, Vasilis
Přispěvatelé:	Apollo - University of Cambridge Repository
Rok vydání:	2023
Předmět:	HLA mismatch eplets antibody mediated rejection (ABMR) Histocompatibility Testing Immunology Medizin kidney transplantation Antibodies molecular mismatch Risk Factors HLA-DQ Antigens Immunology and Allergy Humans Transplantation Homologous donor specific HLA antibodies Child predictive modeling
DOI:	10.17863/cam.95892
Popis:	Peer reviewed: True INTRODUCTION: Rejection 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. METHODS: We 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 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. CONCLUSION: Molecular 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a24f9b4529cf434bdc37bbe34e8eae01 Zobrazit plný text záznamu