title: 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.
abstract: 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.
authors.affiliation: Department of Surgery, HLA Laboratory, Barnes-Jewish Hospital, St. Louis, Missouri, USA.
authors.forename: A
authors.initials: A
authors.lastname: Jaramillo
authors.forename: M A
authors.initials: MA
authors.lastname: Smith
authors.forename: D
authors.initials: D
authors.lastname: Phelan
authors.forename: S
authors.initials: S
authors.lastname: Sundaresan
authors.forename: E P
authors.initials: EP
authors.lastname: Trulock
authors.forename: J P
authors.initials: JP
authors.lastname: Lynch
authors.forename: J D
authors.initials: JD
authors.lastname: Cooper
authors.forename: G A
authors.initials: GA
authors.lastname: Patterson
authors.forename: T
authors.initials: T
authors.lastname: Mohanakumar
mesh_terms: D000906:Antibodies / Q000032:analysis* / Q000276:immunology; D001989:Bronchiolitis Obliterans / Q000209:etiology*; D003165:Complement System Proteins / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D006680:HLA Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D016040:Lung Transplantation; D011183:Postoperative Complications; D011184:Postoperative Period; D013997:Time Factors
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D003165:Complement System Proteins