HLA mismatches influence lung transplant recipient survival, bronchiolitis obliterans and rejection: implications for donor lung allocation

Background: Human leukocyte antigen (HLA) histocompatibility is not considered when placing donor allografts for lung transplantation. We previously reported that fewer individual Class I (HLA-A and -B) and Class II (HLA-DR) antigen mismatches (MM) correlated with improved survival in lung transplant recipients. In this study we evaluated whether the effects of total HLA, Class I and Class II MM were more important determinants of: (1) recipient survival; (2) development of bronchiolitis obliterans (BO); and (3) freedom from acute rejection (AR).

Methods: All adult primary cadaveric lung recipients transplanted between April 1, 1994, and June 30, 2004 entered in the OPTN database were included (n = 9,791). Groups were created based on the total number of HLA, Class I and Class II MM. Recipient survival, freedom from AR and freedom from BO were compared. Univariate data were computed using the Kaplan-Meier method and compared by log-rank test. Multivariate analysis was performed using the Cox proportional hazards method.

Results: Univariate analysis identified significantly improved survival in recipients with fewer total HLA (p < 0.001) and Class I MM (p = 0.005). The incidence of BO was significantly lower in patients with fewer total Class I MM (p = 0.036). AR was influenced only by Class II MM (p = 0.005). By multivariate analysis, total HLA, Class I and Class II MM impacted recipient survival. Total HLA and Class I MM correlated with development of BO. Class II MM correlated with development of AR.

Conclusion: HLA MM are important determinants of lung transplant survival, BO and AR. These data suggest that donor-recipient HLA MM may warrant consideration when allocating organs for lung transplantation.