HLA Epitope Mismatch Load (epMM) Allows Classification of Immunological Risk and Correlates with Patient Survival Following Lung Transplantation (LTx)

Abstract

Currently, the assessment of immunological risk in LTx fails to consider HLA compatibility at molecular level, which would allow greater definition of risk of rejection and help clinicians determine best recipients for transplant. The aim of this study was to evaluate HLAMatchmaker epMM in predicting risk of chronic lung allograft rejection (CLAD) and patient survival following LTx. We retrospectively analysed all 310 primary LTx undertaken between 01/08/2008-31/12/2015. Recipient and donors were high resolution HLA typed for all HLA loci and HLAMatchmaker (v2.1) used to calculate amino acid differences between them. The epMM was calculated based on the number of epitopes present in donor but not in patient. BOS and RAS CLAD phenotypes were determined using the 2019 ISHLT guidelines. EpMM were split into tertiles, with Kaplan Meier analysis and log-ranked tests to compare groups. The total HLA class II epMM range was 0-95, and tertiles used were; 1=0-31, 2=32-50, 3=>51. The lowest HLA class II epMM had significantly better patient survival (p<0.001) when compared to the highest epMM group (fig 1a). When splitting DR (fig 1b) and DQ (fig 1c), both were significant when comparing lowest and highest epMM groups in predicting patient survival (DR p=<0.05, DQ p=<0.005). Looking at time to CLAD, the lowest combined HLA Class I and II epMM group (0-48) demonstrated increased days to CLAD when compared to the higher epMM group (p=0.01). HLA Class I alone was not seen to be significant in any statistical analysis. Recipients with HLA Class II total epMM ≤ 31 demonstrated significantly better patient survival compared to higher epMM. The prospective use of HLA epitope compatibility matching has the potential to identify recipients with lower immunological risk, therefore improving overall patient survival and reducing incidence of CLAD and allowing risk-stratification of immunosuppression.