Introduction: De novo donor-specific HLA antibodies (dnDSA) are recognized as a risk factor for graft loss. Determinants of DSA specificity are generated via the indirect allorecognition pathway. Here, we present supportive data for the relevance of predicted indirectly recognizable HLA epitopes (PIRCHE) to predict dnDSA following kidney transplantation.

Methods: A total of 2,787 consecutive kidney transplantations performed 1995-2015 without preformed DSA have been analyzed. De novo DSA were detected by Luminex^® single antigen assay. HLA epitope mismatches were determined by the PIRCHE and HLAMatchmaker approach and correlated in uni- and multivariate analyses with 10-year allograft survival and incidence of dnDSA.

Results: The correlation of the PIRCHE scores with the count of ABCDRDQ mismatches and with the HLAMatchmaker scores is shown in Fig.1 a, b. The PIRCHE score was a strong predictor of dnDSA (p<0.001, Fig.1 c) and moderately predicted allograft survival (Fig.1 d). When analyzing the predicted impact of high vs. low PIRCHE scores on dnDSA development stratified according to the degree of antigen mismatch at each HLA locus, a clear differentiation could be revealed for HLA-DR and DQ (illustrated according to low vs. high PIRCHE scores (1st vs. 4th quartile) in patients with 1 HLA mismatch at the specific locus, Fig.1 e, f) and to a lesser extent also for HLA-A (p=0.013) and B (p=0.010). In a multivariate Cox regression analysis adjusted for antigen mismatches and HLAMatchmaker epitopes the PIRCHE score could be identified as an independent risk factor for dnDSA (p<0.001).

Conclusions: The PIRCHE score independently from the antigen mismatch and HLAMatchmaker epitopes could be revealed as having a strong predictive value for dnDSA. PIRCHE may help to identify acceptable mismatches with decreased risk of dnDSA and thus improve long-term renal allograft survival.

CITATION INFORMATION: Staeck O, Niemann M, Halleck F, Khadzhynov D, Schönemann C, Reinke P, Spierings E, Budde K, Lachmann N. Improved Outcome of Kidney Transplants by Donor Recipient Matching Based on Predicted Indirectly Recognizable HLA Epitopes. Am J Transplant. 2017;17 (suppl 3).

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