Background 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 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 multicenter database, and to explore whether this relationship varies by transplant indication. Methods 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. Findings HLA-DR mismatch was associated with increased graft failure risk at one year (HR 1.38; 95% CI 1.00–1.90; p=0.048) and five 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 one and five years (HR 2.88, CI 1.34–6.19, p=0.007; HR 1.14, CI 1.03–1.40, p=0.020). In interstitial pneumonia, five-year graft failure risk also rose with mismatch (HR 1.28; CI 1.03–1.58; p=0.026). Interpretation 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.
Otunla et al. (Thu,) studied this question.