Abstract
BackgroundThe 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.MethodsWe 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.ResultsTotal 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).ConclusionsHigh 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.
Highlights
The pathology diagnosis of borderline rejection (BLR) comprises various histologic lesions, ranging from mild inflammation to clinically significant T-cell mediated rejection (TCMR) [1]
From the cohort of 924 kidney transplant recipients (KTRs) transplanted between January 2009 and December 2019, we identified 60 KTRs with BLR in a first indication biopsy, who fulfilled the inclusion criteria (Figure 1)
The 60 KTRs with BLR showed higher total Predicted Indirectly Recognizable HLA Epitopes (PIRCHE) scores compared to the remaining study population of 864 KTRs (p=0.016)
Summary
The pathology diagnosis of borderline rejection (BLR) comprises various histologic lesions, ranging from mild inflammation to clinically significant T-cell mediated rejection (TCMR) [1]. The molecular mechanisms driving TCMR have been demonstrated to be responsible for developing the chronic histologic lesion of interstitial fibrosis/tubular atrophy (IF/TA) [2], which has been associated with graft failure [3, 4]. Nankivell et al showed that despite anti-rejection treatment, BLR was often followed by acute rejection episodes and increased de novo donor‐specific antibodies. Even with the resolution of inflammatory changes in the subsequent biopsies, the BLR was associated with poorer allograft function and survival [5]. The diagnosis of borderline rejection (BLR) ranges from mild inflammation to clinically significant TCMR and is associated with an increased risk of allograft dysfunction. 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
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