Analysis of T and B Cell Epitopes to Predict the Risk of de novo Donor-Specific Antibody (DSA) Production After Kidney Transplantation: A Two-Center Retrospective Cohort Study.

Shintaro Sakamoto,Kosei Horimi,Yuko Miwa,Yoshihiko Watarai,Eric Spierings,Toshihide Tomosugi,Asami Takeda,Kenta Iwasaki,Matthias Niemann,Shunji Narumi,Takaaki Kobayashi,Norihiko Goto

doi:10.3389/fimmu.2020.02000

Abstract

Risk prediction of de novo donor specific antibody (DSA) would be very important for long term graft outcome after organ transplantation. The purpose of this study was to elucidate the association of eplet mismatches and predicted indirectly recognizable HLA epitopes (PIRCHE) scores with de novo DSA production. Our retrospective cohort study enrolled 691 living donor kidney transplantations. HLA-A, B, DRB and DQB eplet mismatches and PIRCHE scores (4 digit of HLA-A, B, DR, and DQ) were determined by HLA matchmaker (ver 2.1) and PIRCHE-II Matching Service, respectively. Weak correlation between eplet mismatches and PIRCHE scores was identified, although both measurements were associated with classical HLA mismatches. Class II (DRB+DQB) eplet mismatches were significantly correlated with the incidence of de novo class II (DR/DQ) DSA production [8/235 (3.4%) in eplet mismatch ≤ 13 vs. 92/456 (20.2%) in eplet mismatch ≥ 14, p < 0.001]. PIRCHE scores were also significantly correlated with de novo class II DSA production [26/318 (8.2%) in PIRCHE ≤ 175 vs. 74/373 (19.8%) in PIRCHE ≥ 176, p < 0.001]. Patients with low levels of both class II eplet mismatches and PIRCHE scores developed de novo class II DSA only in 4/179 (2.2%). Analysis of T cell and B cell epitopes can provide a beneficial information on the design of individualized immunosuppression regimens for prevention of de novo DSA production after kidney transplantation.

Highlights

Chronic antibody-mediated rejection (ABMR) caused by de novo donor specific antibody (DSA) is a major cause of graft failure in solid organ transplantation [1]
The purpose of this study was to examine the association of the eplet mismatch level and predicted indirectly recognizable HLA epitopes (PIRCHE) scores with de novo DSA production after kidney transplantation
De novo DSAs were detected in 114 (16.5%) of the 691 recipients enrolled in this study, including antibodies targeting HLA-class I (n = 14), class I + DR (n = 1), class I+ DQ (n = 2), DR

Summary

Introduction

Chronic antibody-mediated rejection (ABMR) caused by de novo donor specific antibody (DSA) is a major cause of graft failure in solid organ transplantation [1]. Randomized clinical trials have been undertaken in order to explore the efficacies of various treatments for ABMR [2]. Intravenous immunoglobulin (IVIG) and plasmapheresis have been advocated as standard of care, in cases of acute ABMR, there are no effective treatments for chronic ABMR that would prevent the gradual deterioration of graft function [3]. A means to prevent chronic ABMR is likely to be far superior than any available cure [4]. While not all DSAs promote ABMR [5,6,7,8], the development of de novo DSAs remains among the most definitive of the known risk factors that promote this adverse event. Risk prediction of de novo DSA would be important for long term graft outcome

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Conclusion