The influence of HLA matching on graft survival in lung transplant recipients is indication specific: a UNOS database...

Lung transplantation offers definitive treatment for end-stage pulmonary disease, but graft survival remains inferior to other solid organ transplants. A key driver of graft loss is antibody-mediated rejection triggered by donor-recipient human leukocyte antigen (HLA) mismatch. Although HLA matching is not currently used in lung allocation due to organ scarcity and urgency of transplant, understanding its impact could improve risk stratification and outcomes. This study aimed to assess the effect of HLA compatibility on lung graft survival using a large multicentre database and to explore whether this relationship varies by transplant indication.

We conducted a retrospective cohort study of 37 091 lung transplant recipients in the UNOS/OPTN database. Patients were grouped by HLA mismatch (0-2 versus 3-6) and stratified by indication. Multivariate Cox regression and Kaplan-Meier analyses assessed adjusted associations with graft survival.

HLA-DR mismatch was associated with increased graft failure risk at 1 year (hazard ratio (HR) 1.38, 95% CI 1.00-1.90; p=0.048) and 5 years (HR 1.20, 95% CI 1.03-1.40; p=0.020). Stratified analyses showed this effect was found exclusively in those with COPD or interstitial pneumonia. In COPD, HLA-DR mismatch significantly increased failure risk at 1 year (HR 2.88, 95% CI 1.34-6.19; p=0.007). In interstitial pneumonia, 5-year graft failure risk also rose with mismatch (HR 1.28, 95% CI 1.03-1.58; p=0.026).

The present study is the first to demonstrate that HLA-DR mismatch adversely affects lung graft survival in an indication-specific manner. This finding supports the development of indication-specific strategies in post-transplant surveillance and immunosuppression.