Complete and High-Resolution HLA Typing Improves the Accuracy of Post-Transplant Assessment of De Novo Anti-Donor Immune-Mediated Events
1Vall d'Hebron University Hospital, Barcelona, Spain, 2Universitat de Barcelona, Barcelona, Spain, 3Nephrology and Transplantation Laboratory, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, 4Amsterdam University Medical Centers, Amsterdam, Netherlands, 5Charité Universitätsmedizin, Berlin, Germany, 6Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic, 7Nantes Université, Inserm, CHU Nantes, Nantes, France
Meeting: 2022 American Transplant Congress
Abstract number: 933
Keywords: Graft survival, Histocompatibility, Kidney transplantation, Rejection
Topic: Basic Science » Basic Science » 11 - Histocompatibility and Immunogenetics
Session Information
Session Name: Histocompatibility and Immunogenetics
Session Type: Poster Abstract
Date: Sunday, June 5, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: High-resolution (HR) HLA typing using NGS technology has shown to improve the accuracy of assessing donor-recipient compatibility and characterization of pre-transplant anti HLA antibodies with donor- specificity. However, the impact of using complete and HR HLA typing after kidney transplantation (KT) to assess the advent of de novo DSA (dnDSA) and their impact on graft outcomes has not been thoroughly assessed.
*Methods: Multicentre, RCT, available DNA samples were re-evaluated for HR HLA typing using NGS technology at 6 HLA loci (A/B/C/DRB1/DQB1+A1/DPB1). De novo anti-HLA antibodies were assessed by solid phase assays, and dnDSA were classified either:1) as per current clinical practice according to uncomplete Low-resolution (LR) typing at 3 loci (A/B/DRB1), estimating donor C and DQ typing with publicly available frequency tables, or 2) according to complete 6 loci HR typing. The impact on graft outcomes was compared between groups. Mean follow up was 55±15.6 months.
*Results: Using LR HLA typing, 36(15%) patients developed dnDSA (LR_dnDSA+). Out of these, 29(80%) were confirmed to be dnDSA by HR typing (LR_dnDSA+/HR_dnDSA+), whereas 7(20%) were not (LR_dnDSA+/HR_dnDSA-). 3 additional patients were found to show dnDSA not detected by uncomplete LR typing (LR_dnDSA-/HR_dnDSA+).Out of a total of 59 DSA detected in 39 patients, 36(61%) were sconfirmed by both LR and HR HLA typing whereas in 15 cases(25%) LR specificity was not confirmed by HR HLA typing. Moreover, 8(14%) anti-HLA antibodies were identified to be DSA only by HR HLA typing.10/32 (31%) patients displayed class I dnDSA, 19 (59%) class II, and 3 (9%) both class I and II. When assessing main graft outcomes, LR_dnDSA+/HR_dnDSA+ patients were at higher risk of ABMR as compared to patients without dnDSA and LR_dnDSA+/HR_dnDSA- (log Rank<0.001), as well as higher risk of death-censored graft loss (log Rank<0.001). Both LR_dnDSA+ (HR 3.51, 95%CI 1.25-9.85) and LR_dnDSA+/HR_dnDSA+ (HR 4.09, 95%CI 1.45-11.54), but not LR_dnDSA+/HR_dnDSA- independently predicted graft loss together with previous transplants (HR 0.24, 95%CI 0.07-0.84), 12-months eGFR (HR 0.94, 95%CI 0.89-0.98), and previous acute rejection (HR 4.08, 95%CI 1.23-13.52).
*Conclusions: The implementation of HR HLA typing improves the characterization of biologically relevant anti-donor specificities of de novo anti-HLA antibodies and discriminates patients with poorer graft outcomes.
To cite this abstract in AMA style:
Meneghini M, Perona A, Crespo E, Bemelman FJ, Reinke PM, Viklicky O, Giral M, Bestard O. Complete and High-Resolution HLA Typing Improves the Accuracy of Post-Transplant Assessment of De Novo Anti-Donor Immune-Mediated Events [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/complete-and-high-resolution-hla-typing-improves-the-accuracy-of-post-transplant-assessment-of-de-novo-anti-donor-immune-mediated-events/. Accessed June 5, 2025.« Back to 2022 American Transplant Congress