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. 2022 Feb 18:13:788818.
doi: 10.3389/fimmu.2022.788818. eCollection 2022.

High PIRCHE Scores May Allow Risk Stratification of Borderline Rejection in Kidney Transplant Recipients

Ekaterina Lezoeva  1 , Jakob Nilsson  2 , Rudolf Wüthrich  1 , Thomas F Mueller  1 , Thomas Schachtner  1
Affiliations

High PIRCHE Scores May Allow Risk Stratification of Borderline Rejection in Kidney Transplant Recipients

Ekaterina Lezoeva et al. Front Immunol. .

Abstract

Background: The diagnosis of borderline rejection (BLR) ranges from mild inflammation to clinically significant TCMR and is associated with an increased risk of allograft dysfunction. Currently, there is no consensus regarding its treatment due in part to a lack of biomarkers to identify cases with increased risk for immune-mediated injury.

Methods: We identified 60 of 924 kidney transplant recipients (KTRs) with isolated and untreated BLR. We analyzed the impact of predicted indirectly recognizable HLA epitopes (PIRCHE) score on future rejection, de novo DSA development, and recovery to baseline allograft function. Additionally, we compared the outcomes of different Banff rejection phenotypes.

Results: Total PIRCHE scores were significantly higher in KTRs with BLR compared to the entire study population (p=0.016). Among KTRs with BLR total PIRCHE scores were significantly higher in KTRs who developed TCMR/ABMR in follow-up biopsies (p=0.029). Notably, the most significant difference was found in PIRCHE scores for the HLA-A locus (p=0.010). PIRCHE scores were not associated with the development of de novo DSA or recovery to baseline allograft function among KTRs with BLR (p>0.05). However, KTRs under cyclosporine-based immunosuppression were more likely to develop de novo DSA (p=0.033) than those with tacrolimus, whereas KTRs undergoing retransplantation were less likely to recover to baseline allograft function (p=0.003).

Conclusions: High PIRCHE scores put KTRs with BLR at an increased risk for future TCMR/ABMR and contribute to improved immunological risk stratification. The benefit of anti-rejection treatment, however, needs to be evaluated in future studies.

Keywords: ABMR; TCMR; borderline rejection; de novo DSA; epitope matching.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Patient inclusion and exclusion algorithm.
Figure 2
Figure 2
Distribution of total PIRCHE scores compared to total HLA-mismatches. PIRCHE scores and the number of HLA-mismatches were calculated from HLA class I (HLA-A, B, C) and HLA class II (HLA-DR, DQ) mismatches. Median PIRCHE scores for 4, 5, 6, 7, 8, 9, and 10 HLA-mismatches were 76.15, 81.07, 77.63, 101.97, 94.66, 114.56, and 112.45, respectively.
Figure 3
Figure 3
(A, B) Higher total PIRCHE scores (A) and PIRCHE scores for HLA-A locus mismatches (B) among KTRs with BLR who develop future TCMR/ABMR. Boxplots show median, interquartile range (IQR), and 95th percentile. ** significance level p<0.01.
Figure 4
Figure 4
(A, B) Higher total PIRCHE scores (A) and PIRCHE scores for HLA-A locus mismatches (B) among KTRs with isolated tubulitis compared to KTRs with inflammation and tubulitis. Boxplots show median, interquartile range (IQR), and 95th percentile. * significance level p<0.05; ** significance level p<0.01.
See this image and copyright information in PMC

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