Mismatches at the HLA-DR and HLA-B Loci Are Risk Factors for Acute Rejection after Lung Transplantation

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Abstract
Early high-grade acute rejections (pathologic grade A2 or A3) in recipients of lung allografts are a major risk factor for the subsequent development of obliterative bronchiolitis (OB). We analyzed the risk factors for high-grade acute rejections in 152 recipients of single (100) or bilateral (52) lung allografts transplanted at our institution between 1990 and 1996. Using Kaplan-Meier product limit estimate analysis, there was a 50% probability of grade A2 or A3 rejection by 1 yr after transplant. By univariate analysis, the only significant predictor of early high-grade rejections was the presence of one or more mismatches at the HLA-DR locus (p = 0.038). This association was confirmed using 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, recipients with one or more matches at the HLA-DR locus had a lower cumulative rate of grade A2 or A3 rejections during the first year compared with 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 lower 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 protocols that are more effective in preventing recipient T-cell activation by donor alloantigens are likely to reduce the rate of high-grade acute rejections in recipients of lung transplants, and may directly impact on the time to onset of OB.