(312) Risk Stratifying by DQA and Risk Epitope Mismatches in Lung Transplantation

Purpose DQA mismatches, defined by the presence of a donor DQA antigen not present in the recipient, and risk epitope mismatches, defined by the presence of a donor DQA1*05/DQB1*03:01 or DQA1*05/DQB1*02 antigen not present in the recipient, are associated with de novo donor specific antibodies (dnDSA). Our aim was to stratify lung transplant recipients (LTR) by their DQA and risk epitope mismatches to determine the impact on dnDSA and chronic lung allograft dysfunction (CLAD). Methods First-time, adult LTR from 2014-2019 with complete human leukocyte antigen (HLA) typing and post-transplant HLA antibody testing were included. LTR were divided into 4 risk categories: green if no DQA or risk epitope mismatches present; yellow if only a DQA mismatch present; orange if only one of the risk epitope mismatches present; or red if 2 risk epitope mismatches or one risk epitope mismatch and DQA mismatch present. dnDSA-free and CLAD-free survival were compared among the risk categories using log rank test. Results Of the 859 LTR included in the study, 158 (18%) were risk category green, 410 (48%) risk category yellow, 29 (3%) risk category orange, and 262 (31%) risk category red. dnDSA-free survival was significantly shorter among LTR in risk category red (Figure 1, log-rank p-value<0.001). CLAD-free survival did not differ among the 4 risk categories (Figure 2, log-rank p-value=0.57). Conclusion Stratifying LTR by DQA and risk epitope mismatches predicts dnDSA but not CLAD development, which may indicate a "two-hit hypothesis" for CLAD driven by dnDSA. Further studies are required to determine if avoiding risk category red lung transplants is a feasible strategy to reduce dnDSA.