Long-term outcome of lung transplantation is predicted by the number of HLA-DR mismatches

Background. The importance of HLA mismatch in determining long-term outcome in lung transplantation remains largely uncertain. Methods. A retrospective analysis of 102 consecutive primary lung transplan ts was performed to identify risk factors for poor long-term outcome after lung transplantation defined as graft survival and bronchiolitis obliterans syndrome (BOS) stage I and II. Variables included were patient characteris tics (age, sex, prior diagnosis), the number of HLA mismatches between dono r and recipient, cold ischemic time, cyto-megalovirus serologic concordance , number of acute rejections, and time to first rejection. Variables carryi ng significance in a univariate analysis were subjected to a proportional h azard regression analysis. Results. In the multivariate analysis, arn increased number of acute reject ions correlated positively with decreased graft survival (risk ratio [RR]=1 .25; 95% confidence interval [CI], 1.05-1.5; P=0.011), development of BOS s tage I (RR=1.36/episode; 95% CI, 1.16-1.58; P<0,001), and BOS stage II (RR= 1.42/episode; 95% CI, 1.2-1.67; P<0,001), An increased time to rejection co rrelated positively with reduced graft survival (RR=1.03/day; 95% CI, 1.01- 1.06; P=0,02), and BOS stage I and II (both RR=1.04/day; 95% CI, 1.01-1.07; P<0,005), Compared with 2 HLA-DR mismatches, 0 or 1 mismatch was associate d with improved graft survival (RR=0.43; 95% CI, 0.19-0.98; P=0,045) and pr otected against development of BOS stage I (RR=0.47; 95% CI, 0.23-0.98; P=0 .044) and BOS stage II (RR=0.35; 95% CI, 0.15-0.83; P=0.017). Conclusions. HLA-DR mismatching appears to be a risk. factor for the develo pment of BOS and graft loss, Improved outcome after lung transplantation mi ght be achieved with prospective matching for HLA-DR. Alternatively, the am ount and type of immunosuppressive drugs may be guided by the degree of HLA -DR (mis)matching.