Mismatches at the HLA-DR and HLA-B loci are risk factors for acute rejection after lung transplantation

Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1833-7. doi: 10.1164/ajrccm.157.6.9707007.


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.

MeSH terms

  • Acute Disease
  • Adult
  • Bronchiolitis Obliterans / etiology
  • Bronchiolitis Obliterans / immunology
  • Female
  • Graft Rejection / etiology*
  • Graft Rejection / immunology
  • HLA-B Antigens / analysis*
  • HLA-DR Antigens / analysis*
  • Histocompatibility Testing*
  • Humans
  • Lung Transplantation*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Proportional Hazards Models
  • Risk Factors


  • HLA-B Antigens
  • HLA-DR Antigens