Transplant Trial Watch

Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression.

Snanoudj, R., et al.

Kidney International 2019; 95(6): 1471-1485.

This is a substudy of a randomised controlled trial that aimed to investigate the effects of switching from cyclosporine (Csa) to everolimus after kidney transplantation. The primary objective of this study was to examine whether mismatched epitope load could be used as a tool for identifying patients at high risk of developing donor-specific antibodies following a reduction in immunosuppressive agents.

Patients in the original trial were randomised into two groups: conversion from CsA to everolimus or continued CsA therapy.

175 kidney transplant recipients

The outcomes of interest included patient survival; graft survival; the evaluation of human leukocyte antigen (HLA) compatibility with antigenic, allelic, and epitopic mismatches; factors associated with the development of de novo donor-specific antibodies (dnDSAs); and the identification of the most immunogenic epitopes.

83.8 ±27.9 months (mean)

CET Conclusions
This interesting paper reports a substudy from a randomised controlled trial of conversion from cyclosporine to everolimus following renal transplant. The authors investigated the role of mismatched epitope burden on risk of development of donor-specific antibodies following immunosuppression reduction. Risk of developing de-novo DSA was increased 12-fold when there was an epitope mismatch load of greater than 27, making it a much better predictor of sensitization than HLA-antigen mismatch alone. These results suggest that epitope mismatch burden may be a useful tool in decisions to minimize immunosuppression (or even withdraw it altogether following transplant failure). It should be noted that this is a post-hoc study, and these results need to be validated in prospective studies of immunosuppression minimization.

Trial registration
EudraCT - 2009–011473‐33

Funding source
Not reported