Eplet-Predicted Antigens: An Attempt to Introduce Eplets into Unacceptable Antigen Determination and Calculated Panel-Reactive Antibody Calculation Facilitating Kidney Allocation

Overview

Journal Diagnostics (Basel)

Specialty Radiology

Date 2022 Dec 23

PMID 36552990

Authors

Wenrui Wu

Huanxi Zhang

Jinghong Tan

Qian Fu

Jun Li

Chenglin Wu

Huiting Huang

Bowen Xu

Liuting Ling

Longshan Liu

Xiaojun Su

Changxi Wang

Affiliations

Soon will be listed here.

Abstract

(1) Calculated panel-reactive antibody (CPRA) is a measure of sensitization based on unacceptable antigens (UAs). Determination of UAs based on single-antigen bead assays at allele or antigen levels may be inappropriate. We aimed to introduce eplets for better assessment of sensitization; (2) 900 recipients and 1427 donors were enrolled for candidate or donor pools, respectively. Eplets were from the HLA Epitope Registry. UAs were determined by anti-HLA antibodies identified using LIFECODES Single Antigen (LSA) kits. CPRA values were calculated using a simplified method of donor filtering; (3) HLA antigens containing all eplets of an HLA antigen in LSA kits (LSA antigen) were defined as eplet-predicted (EP) antigens, the reactivity of which could be predicted by that LSA antigen. High reactivity concordance was found between LSA and EP antigens. More HLA antigens were covered by EP antigens in the population than LSA antigens. CPRA values at the EP level were higher than at the allele level and lower than at the antigen level. The EP antigens facilitated UA determination for non-LSA antigens and avoided acute rejection; (4) UA determination using EP antigens can lead to more accurate assessment of sensitization, enabling a high probability of compatible organs and a low risk of adverse outcomes.

References

Kumar S, Doss S, Stephen S, Pratheeba M, Jeyaseelan L, Daniel D . The challenge of using the virtual crossmatch as a singular tool for the detection of Anti-HLA antibodies- A study from a tertiary care institute from South India. Transpl Immunol. 2020; 65:101349. DOI: 10.1016/j.trim.2020.101349. View

Caro-Oleas J, Gonzalez-Escribano M, Gonzalez-Roncero F, Acevedo-Calado M, Cabello-Chaves V, Gentil-Govantes M . Clinical relevance of HLA donor-specific antibodies detected by single antigen assay in kidney transplantation. Nephrol Dial Transplant. 2011; 27(3):1231-8. DOI: 10.1093/ndt/gfr429. View

Gebel H, Bray R . HLA antibody detection with solid phase assays: great expectations or expectations too great?. Am J Transplant. 2014; 14(9):1964-75. DOI: 10.1111/ajt.12807. View

Duquesnoy R, Askar M . HLAMatchmaker: a molecularly based algorithm for histocompatibility determination. V. Eplet matching for HLA-DR, HLA-DQ, and HLA-DP. Hum Immunol. 2007; 68(1):12-25. PMC: 2527859. DOI: 10.1016/j.humimm.2006.10.003. View

Senev A, Coemans M, Lerut E, Van Sandt V, Kerkhofs J, Daniels L . Eplet Mismatch Load and Occurrence of Donor-Specific Anti-HLA Antibodies, Rejection, and Graft Failure after Kidney Transplantation: An Observational Cohort Study. J Am Soc Nephrol. 2020; 31(9):2193-2204. PMC: 7461684. DOI: 10.1681/ASN.2020010019. View

Cecka J . Calculated PRA (CPRA): the new measure of sensitization for transplant candidates. Am J Transplant. 2009; 10(1):26-9. DOI: 10.1111/j.1600-6143.2009.02927.x. View

Duquesnoy R, Gebel H, Woodle E, Nickerson P, Baxter-Lowe L, Bray R . High-Resolution HLA Typing for Sensitized Patients: Advances in Medicine and Science Require Us to Challenge Existing Paradigms. Am J Transplant. 2015; 15(10):2780-1. DOI: 10.1111/ajt.13376. View

Zavyalova D, Abraha J, Rao P, Morris G . Incidence and impact of allele-specific anti-HLA antibodies and high-resolution HLA genotyping on assessing immunologic compatibility. Hum Immunol. 2021; 82(3):147-154. DOI: 10.1016/j.humimm.2021.01.002. View

Sypek M, Kausman J, Holt S, Hughes P . HLA Epitope Matching in Kidney Transplantation: An Overview for the General Nephrologist. Am J Kidney Dis. 2017; 71(5):720-731. DOI: 10.1053/j.ajkd.2017.09.021. View

10.

Huber L, Lachmann N, Niemann M, Naik M, Liefeldt L, Glander P . Pretransplant virtual PRA and long-term outcomes of kidney transplant recipients. Transpl Int. 2015; 28(6):710-9. DOI: 10.1111/tri.12533. View

11.

Kransdorf E, Pando M, Stewart D, Lindblad K, Bray R, Murphey C . Stem cell donor HLA typing improves CPRA in kidney allocation. Am J Transplant. 2020; 21(1):138-147. DOI: 10.1111/ajt.16156. View

12.

Tonelli M, Wiebe N, Knoll G, Bello A, Browne S, Jadhav D . Systematic review: kidney transplantation compared with dialysis in clinically relevant outcomes. Am J Transplant. 2011; 11(10):2093-109. DOI: 10.1111/j.1600-6143.2011.03686.x. View

13.

Picascia A, Grimaldi V, Napoli C . From HLA typing to anti-HLA antibody detection and beyond: The road ahead. Transplant Rev (Orlando). 2016; 30(4):187-94. DOI: 10.1016/j.trre.2016.07.007. View

14.

Tambur A, Audry B, Antoine C, Suberbielle C, Glotz D, Jacquelinet C . Harnessing Scientific and Technological Advances to Improve Equity in Kidney Allocation Policies. Am J Transplant. 2017; 17(12):3149-3158. DOI: 10.1111/ajt.14389. View

15.

Ponticelli C . The impact of cold ischemia time on renal transplant outcome. Kidney Int. 2015; 87(2):272-5. DOI: 10.1038/ki.2014.359. View

16.

Schinstock C, Gandhi M, Stegall M . Interpreting Anti-HLA Antibody Testing Data: A Practical Guide for Physicians. Transplantation. 2016; 100(8):1619-28. PMC: 4961613. DOI: 10.1097/TP.0000000000001203. View

17.

Ziemann M, Hessler N, Konig I, Lachmann N, Dick A, Ditt V . Unacceptable human leucocyte antigens for organ offers in the era of organ shortage: influence on waiting time before kidney transplantation. Nephrol Dial Transplant. 2017; 32(5):880-889. DOI: 10.1093/ndt/gfw462. View

18.

Bosanquet J, Witt C, Bemiss B, Byers D, Yusen R, Patterson A . The impact of pre-transplant allosensitization on outcomes after lung transplantation. J Heart Lung Transplant. 2015; 34(11):1415-22. PMC: 4619119. DOI: 10.1016/j.healun.2015.06.003. View

19.

Tambur A, Claas F . HLA epitopes as viewed by antibodies: what is it all about?. Am J Transplant. 2015; 15(5):1148-54. DOI: 10.1111/ajt.13192. View

20.

Tambur A . HLA-Epitope Matching or Eplet Risk Stratification: The Devil Is in the Details. Front Immunol. 2018; 9:2010. PMC: 6128220. DOI: 10.3389/fimmu.2018.02010. View