Can PIRCHE-II Matching Outmatch Traditional HLA Matching?

Christian Unterrainer,Matthias Niemann,Caner Süsal,Nils Lachmann,Bernd Döhler

doi:10.3389/fimmu.2021.631246

Christian Unterrainer, Matthias Niemann + Show 3 more

Open Access

https://doi.org/10.3389/fimmu.2021.631246

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Abstract

We analyzed in a cohort of 68,606 first deceased donor kidney transplantations reported to the Collaborative Transplant Study whether an epitope-based matching of donor-recipient pairs using the Predicted Indirectly ReCognizable HLA Epitopes algorithm (PIRCHE-II) is superior to currently applied HLA antigen matching. PIRCHE-II scores were calculated based on split antigen HLA-A, -B, -DRB1 typing and adjusted to the 0–6 range of HLA mismatches. PIRCHE-II scores correlated strongly with the number of HLA mismatches (Spearman ρ = 0.65, P < 0.001). In multivariable analyses both parameters were found to be significant predictors of 5-year death-censored graft loss with high prognostic power [hazard ratio (HR) per adjusted PIRCHE-II score = 1.102, per HLA mismatch = 1.095; z-value PIRCHE-II: 9.8, HLA: 11.2; P < 0.001 for both]. When PIRCHE-II scores and HLA mismatches were analyzed simultaneously, their predictive power decreased but remained significant (PIRCHE-II: P = 0.002; HLA: P < 0.001). Influence of PIRCHE-II was especially strong in presensitized and influence of HLA mismatches in non-sensitized recipients. If the level of HLA-incompatibility was low (0–3 mismatches), PIRCHE-II scores showed a low impact on graft survival (HR = 1.031) and PIRCHE-II matching did not have additional significant benefit (P = 0.10). However, if the level of HLA-incompatibility was high (4–6 mismatches), PIRCHE-II improved the positive impact of matching compared to applying the traditional HLA matching alone (HR = 1.097, P = 0.005). Our results suggest that the PIRCHE-II score is useful and can be included into kidney allocation algorithms in addition to HLA matching; however, at the resolution level of HLA typing that is currently used for allocation it cannot fully replace traditional HLA matching.

Highlights

Human leukocyte antigen (HLA) matching continues to be part of the major kidney allocation systems
It allows calculation of an epitope load score based on donor HLA epitopes that can be presented by HLA-DRB1 molecules of the recipient, but are not found in the recipient’s own HLA-A, -B, -C, -DRB1 and -DQB1 alleles, modeling the indirect pathway of allorecognition by CD4+ T cells
The demographics of 68,606 deceased donor kidney transplantations with a mean follow-up of 6.9 years performed at 236 European Collaborative Transplant Study (CTS) centers in 24 countries and categorized according to adjusted PIRCHE-II scores are shown in Table 1 and in more detail in Supplementary Table 1

Summary

Introduction

Human leukocyte antigen (HLA) matching continues to be part of the major kidney allocation systems. To improve the precision of matching between donor and recipient and the knowledge on HLA incompatibilities that are relevant for rejection of kidney allografts, several theoretical and experimentbased algorithms have been developed (7–11). The Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE-II) algorithm is one of these promising theoretical approaches and matching based on this algorithm was shown to have potential to improve graft survival (12). It allows calculation of an epitope load score based on donor HLA epitopes that can be presented by HLA-DRB1 molecules of the recipient, but are not found in the recipient’s own HLA-A, -B, -C, -DRB1 and -DQB1 alleles, modeling the indirect pathway of allorecognition by CD4+ T cells

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