MISMATCHES AT THE HLA-DR AND HLA-B LOCI ARE RISK-FACTORS FOR ACUTE REJECTION AFTER LUNG TRANSPLANTATION

Early high-grade acute rejections (pathologic grade A2 or A3) in recip ients of lung allografts are a major risk factor for the subsequent de velopment of obliterative bronchiolitis (OB). We analyzed the risk fac tors for high-grade acute rejections in 152 recipients of single (100) or bilateral (52) lung allografts transplanted at our institution bet ween 1990 and 1996. Using Kaplan-Meier product limit estimate analysis , there was a 50% probability of grade A2 ol A3 rejection by 1 yr afte r transplant. By univariate analysis, the only significant predictor o f early high-grade rejections was the presence of one or more mismatch es at the HLA-DR locus (p = 0.038). This association was confirmed usi ng the Cox proportional hazards model for multivariable analysis, with HLA-DR locus mismatch being the only risk factor identified for high- grade rejection (p = 0.036). Using repeated rejection analysis, recipi ents with one or more matches at the HLA-DR locus had a lower cumulati ve rate of grade A2 or A3 rejections during the first year compared wi th recipients with no matches at the HLA-DR locus (0.73 versus 1.32). In addition, recipients with one or more HLA-B locus matches had a low er cumulative rate of grade A2 or A3 rejections in the first year than did recipients with no matches at the HLA-B locus (0.59 versus 1.30). These results indicate that mismatches between donors and recipients at the HLA-DR and HLA-B loci are important risk factors for early high -grade rejections after lung transplantation. Immunosuppressive protoc ols that are more effective in preventing recipient T-cell activation by donor alloantigens are likely to reduce the rate of high-grade acut e rejections in recipients of lung transplants, and may directly impac t on the time to onset of OB.