Can Avoiding So-Called HLA High Risk Epitope Mismatches (REM) Improve Lung Transplant (LTx) Outcomes?

PURPOSE: HLA epitope mismatches can determine risk of graft rejection and de novo Donor Specific Antibodies (dnDSA) formation. Recently (McCaughan 2018) noted some epitopes posed a greater risk of developing dnDSA post-LTx and assumed this correlated with CLAD and survival. Using these reported REM we aim to determine associations between REM and actual LTx outcomes. METHODS: We retrospectively analysed all 310 primary LTx undertaken Aug 2008-Dec 2015, with both patients and donors' high resolution HLA typed for all HLA loci. Using HLAMatchmaker (v2.1), LTx were assessed for the presence of REM (45GE3 or 45EV/55PP) and DQA1*05. BOS and RAS were determined using the most recent 2019 ISHLT guidelines. Kaplan Meier analysis with log-ranked tests compared groups. RESULTS: Within our cohort, 82 (27%) LTx occurred in the presence of a REM from the donor. Of these, 43 developed CLAD (BOS n=28 RAS n=15). REM was not a predictor of overall patient survival (fig 1a) (p=0.52) or time to CLAD (fig 1b) (p=0.32). As previously published (McCaughan 2018) the development of dnDSA directed to HLA-DQ was frequent (ie 75% of those tested post-LTx) this did not correlate to time to CLAD or overall patient survival in our cohort. CONCLUSION: Although avoiding REM has been reported to reduce risk of dnDSA following LTx, in our cohort this does not strongly correlate to overall patient survival or time to CLAD. Further studies are still warranted to identify the riskiest of epitopes to avoid in LTx and how the correlate to LTx outcomes.