The influence of HLA matching on graft survival in lung transplant recipients is indication specific

<bold>Purpose:</bold> This study aimed to determine the relationship between HLA matching and lung graft survival using a large-scale multi-center database (UNOS/OPTN) and multivariate logistic analysis. The secondary aim was to determine whether this relationship was influenced by transplant indication. <bold>Methods:</bold> This retrospective observational analysis was performed using 26,312 lung transplant recipients from the UNOS/OPTN database. Patients were divided into two groups based on number of HLA mismatches (0-3 mismatches vs 4-6 mismatches) and subcategorized by indication. Risk-adjusted outcomes were assessed by multivariate Cox analysis adjusting for donor and recipient characteristics and visualized using Kaplan-Meier survival curves. <bold>Results:</bold> Increased HLA mismatch was associated with reduced allograft survival. Adjusted models found that the total HLA mismatch >3 increased the mortality hazard at 15 years (HR 1·05, 95% CI 1-1·1, p <0·05) and 20 years (HR 1·05, 95 CI 1-1·1, p<0·01). Pulmonary hypertension was the only indication with a statistically significant association between HLA mismatch and graft survival. Allografts in patients with pulmonary hypertension and 0-3 mismatches survived for 401 days longer than those with 4-6 mismatches (p=0·02). Multivariate analysis at 20 years produced a mortality hazard of 1·2 (CI 1·03-1·4, p<0·05). <bold>Conclusions:</bold> Increased HLA mismatch reduced graft survival. When stratified by indication, this association was preserved exclusively in pulmonary hypertension. This finding is of potential clinical relevance to the management of this subsection of lung transplant recipients, impacting organ allocation, transplant surveillance and immunosuppression protocols.