Human leukocyte antigen mismatch on lung transplantation outcomes

Objectives: Human leucocyte antigen (HLA) mismatch is a known risk factor for renal transplantation; however, there are conflicting and limited data on its ramifications within lung transplantation (LTx). Therefore, our study evaluated the effects of total HLA, HLA-A, -B and -DR mismatches on LTx outcomes.

Methods: We retrospectively examined the United Network for Organ Sharing database for adult patients who had undergone LTx for the first time between January 2005 and July 2021. Total HLA mismatch (0-3, 4, 5 and 6) and HLA locus mismatch (0-1 and 2) were analysed, with the end points of interest being mortality and bronchiolitis obliterans syndrome (BOS) development.

Results: Kaplan-Meier curve analysis found a significant difference in both overall survival (n = 27 651; 11 830 events) and BOS development (n = 25 444; 8901 events) for the total number of HLA (P < 0.001, P < 0.001), HLA-A (P < 0.001, P = 0.006) and HLA-DR (P < 0.001, P < 0.001) mismatches. With reference to 0-3 total HLA mismatches, multivariable Cox regression model found that 6 mismatches had an increased risk of mortality (P = 0.002) while 4 (P = 0.010), 5 (P = 0.007) and 6 (P < 0.001) mismatches had an increased risk of BOS. HLA-B mismatch was not associated with an increased mortality (P = 0.975) or BOS risk (P = 0.512).

Conclusions: This study demonstrates a significant relationship between increased HLA mismatches and BOS development, with decreased overall survival only apparent with 6 mismatches. HLA-A and -DR mismatches were associated with an increased risk of mortality and BOS development compared to groups with at least 1 locus match.