Development of ELISA-detected anti-HLA antibodies precedes the development of bronchiolitis obliterans syndrome and correlates with progressive decline in pulmonary function after lung transplantation

Transplantation. 1999 Apr 27;67(8):1155-61. doi: 10.1097/00007890-199904270-00012.


Background: Development of anti-HLA antibodies after lung transplantation (LT) is thought to play an important role in the etiology of bronchiolitis obliterans syndrome (BOS). However, a cause-effect relationship between anti-HLA antibodies and BOS has not been established. This study was conducted to determine the temporal relationship between the development of anti-HLA antibodies and BOS after LT, and to determine the antigenic specificity of the antibodies developed in BOS patients.

Methods: Sera from 15 BOS+ LT patients and 12 BOS- LT patients were obtained before LT and collected again at 6, 12, 24, 36, and 48 months after LT. Anti-HLA antibodies were detected by the PRA-STAT ELISA system and by complement-dependent cytotoxicity assays. Anti-HLA reactivity was further characterized by flow cytometry and absorption/elution with human platelets.

Results: When analyzed by ELISA, 10 of 15 BOS+ patients developed anti-HLA antibodies, whereas 0 of 12 BOS- patients developed anti-HLA antibodies (P<0.001). When analyzed by complement-dependent cytotoxicity, only 2 of 15 BOS+ patients developed anti-HLA antibodies and 1 of 12 BOS- patients developed anti-HLA antibodies (P = 0.99). There was a significant difference of 20.1 months between the time of anti-HLA antibody detection and the time of BOS diagnosis (P = 0.005). A progressive decrease in pulmonary function correlated with a progressive increase in the anti-HLA reactivity 36 months after LT. The anti-HLA reactivity was directed to one of the donor HLA class I antigens and to other unrelated HLA class I antigens. No anti-HLA reactivity was found against HLA class II molecules.

Conclusions: Our study indicates that anti-HLA class I antibodies play an important role in the pathogenesis of BOS and that monitoring of anti-HLA class I antibody development by a highly sensitive assay such as the PRA-STAT ELISA after LT can provide an early identification of an important subset of LT patients with an increased risk of developing BOS.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies / analysis*
  • Antibodies / immunology
  • Bronchiolitis Obliterans / etiology*
  • Complement System Proteins / physiology
  • Cytotoxicity, Immunologic / physiology
  • Enzyme-Linked Immunosorbent Assay
  • HLA Antigens / immunology*
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Lung / physiopathology*
  • Lung Transplantation*
  • Postoperative Complications*
  • Postoperative Period
  • Time Factors


  • Antibodies
  • HLA Antigens
  • Histocompatibility Antigens Class I
  • Complement System Proteins