PMID- 36776892 OWN - NLM STAT- MEDLINE DCOM- 20230214 LR - 20230307 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 14 DP - 2023 TI - Extended genomic HLA typing identifies previously unrecognized mismatches in living kidney transplantation. PG - 1094862 LID - 10.3389/fimmu.2023.1094862 [doi] LID - 1094862 AB - INTRODUCTION: Antibody mediated rejection (ABMR) is the most common cause of long-term allograft loss in kidney transplantation (KT). Therefore, a low human leukocyte antigen (HLA) mismatch (MM) load is favorable for KT outcomes. Hitherto, serological or low-resolution molecular HLA typing have been adapted in parallel. Here, we aimed to identify previously missed HLA mismatches and corresponding antibodies by high resolution HLA genotyping in a living-donor KT cohort. METHODS: 103 donor/recipient pairs transplanted at the University of Leipzig Medical Center between 1998 and 2018 were re-typed using next generation sequencing (NGS) of the HLA loci -A, -B, -C, -DRB1, -DRB345, -DQA1, -DQB1, -DPA1, and -DPB1. Based on these data, we compiled HLA MM counts for each pair and comparatively evaluated genomic HLA-typing with pre-transplant obtained serological/low-resolution HLA (=one-field) typing results. NGS HLA typing (=two-field) data was further used for reclassification of de novo HLA antibodies as "donor-specific". RESULTS: By two-field HLA re-typing, we were able to identify additional MM in 64.1% (n=66) of cases for HLA loci -A, -B, -C, -DRB1 and -DQB1 that were not observed by one-field HLA typing. In patients with biopsy proven ABMR, two-field calculated MM count was significantly higher than by one-field HLA typing. For additional typed HLA loci -DRB345, -DQA1, -DPA1, and -DPB1 we observed 2, 26, 3, and 23 MM, respectively. In total, 37.3% (69/185) of de novo donor specific antibodies (DSA) formation was directed against these loci (DRB345 ➔ n=33, DQA1 ➔ n=33, DPA1 ➔ n=1, DPB1 ➔ n=10). CONCLUSION: Our results indicate that two-field HLA typing is feasible and provides significantly more sensitive HLA MM recognition in living-donor KT. Furthermore, accurate HLA typing plays an important role in graft management as it can improve discrimination between donor and non-donor HLA directed cellular and humoral alloreactivity in the long range. The inclusion of additional HLA loci against which antibodies can be readily detected, HLA-DRB345, -DQA1, -DQB1, -DPA1, and -DPB1, will allow a more precise virtual crossmatch and better prediction of potential DSA. Furthermore, in living KT, two-field HLA typing could contribute to the selection of the immunologically most suitable donors. CI - Copyright (c) 2023 Lehmann, Pehnke, Weimann, Bachmann, Dittrich, Petzold, Furst, de Fallois, Landgraf, Henschler, Lindner, Halbritter, Doxiadis, Popp and Munch. FAU - Lehmann, Claudia AU - Lehmann C AD - Institute for Transfusion Medicine, University Hospital Leipzig, Leipzig, Germany. FAU - Pehnke, Sarah AU - Pehnke S AD - Division of Nephrology, Department of Internal Medicine, University of Leipzig Medical Center, Leipzig, Germany. FAU - Weimann, Antje AU - Weimann A AD - Division of Visceral Surgery and Transplantation Medicine, University of Leipzig Medical Center, Leipzig, Germany. FAU - Bachmann, Anette AU - Bachmann A AD - Division of Nephrology, Department of Internal Medicine, University of Leipzig Medical Center, Leipzig, Germany. FAU - Dittrich, Katalin AU - Dittrich K AD - Department of Pediatric Nephrology, University of Leipzig Medical Center, Leipzig, Germany. FAU - Petzold, Friederike AU - Petzold F AD - Division of Nephrology, Department of Internal Medicine, University of Leipzig Medical Center, Leipzig, Germany. FAU - Furst, Daniel AU - Furst D AD - Institute of Transfusion Medicine, University of Ulm, Ulm, Germany. FAU - de Fallois, Jonathan AU - de Fallois J AD - Division of Nephrology, Department of Internal Medicine, University of Leipzig Medical Center, Leipzig, Germany. FAU - Landgraf, Ramona AU - Landgraf R AD - Institute for Transfusion Medicine, University Hospital Leipzig, Leipzig, Germany. FAU - Henschler, Reinhard AU - Henschler R AD - Institute for Transfusion Medicine, University Hospital Leipzig, Leipzig, Germany. FAU - Lindner, Tom H AU - Lindner TH AD - Division of Nephrology, Department of Internal Medicine, University of Leipzig Medical Center, Leipzig, Germany. FAU - Halbritter, Jan AU - Halbritter J AD - Division of Nephrology, Department of Internal Medicine, University of Leipzig Medical Center, Leipzig, Germany. AD - Department of Nephrology and Medical Intensive Care, Charite Universitatsmedizin Berlin, Berlin, Germany. FAU - Doxiadis, Ilias AU - Doxiadis I AD - Institute for Transfusion Medicine, University Hospital Leipzig, Leipzig, Germany. FAU - Popp, Bernt AU - Popp B AD - Institute of Human Genetics, University of Leipzig, Leipzig, Germany. FAU - Munch, Johannes AU - Munch J AD - Division of Nephrology, Department of Internal Medicine, University of Leipzig Medical Center, Leipzig, Germany. AD - Department of Nephrology and Medical Intensive Care, Charite Universitatsmedizin Berlin, Berlin, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230127 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (HLA-DQ beta-Chains) SB - IM MH - Humans MH - *Kidney Transplantation/adverse effects MH - Histocompatibility Antigens Class I/genetics MH - Histocompatibility Antigens Class II/genetics MH - Histocompatibility Testing/methods MH - HLA-DQ beta-Chains/genetics MH - Genomics PMC - PMC9911689 OTO - NOTNLM OT - HLA mismatch OT - HLA typing OT - NGS OT - donor specific antibodies OT - epitope matching OT - kidney transplantation COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/02/14 06:00 MHDA- 2023/02/15 06:00 PMCR- 2023/01/01 CRDT- 2023/02/13 03:26 PHST- 2022/11/10 00:00 [received] PHST- 2023/01/12 00:00 [accepted] PHST- 2023/02/13 03:26 [entrez] PHST- 2023/02/14 06:00 [pubmed] PHST- 2023/02/15 06:00 [medline] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2023.1094862 [doi] PST - epublish SO - Front Immunol. 2023 Jan 27;14:1094862. doi: 10.3389/fimmu.2023.1094862. eCollection 2023.