title: Implications for human leukocyte antigen antibodies after lung transplantation: a 10-year experience in 441 patients.
abstract: BACKGROUND
  Long-term survival after lung transplant is limited by the development of chronic and progressive airflow obstruction, a condition known as bronchiolitis obliterans syndrome (BOS). While prior studies strongly implicate cellular rejection as a strong risk factor for BOS, less is known about the clinical significance of human leukocyte antigen (HLA) antibodies and donor HLA-specific antibodies in long-term outcomes.
  
  
  METHODS
  A single-center cohort of 441 lung transplant recipients, spanning a 10-year period, was prospectively screened for HLA antibodies after transplant using flow cytometry-based methods. The prevalence of and predictors for HLA antibodies were determined. The impact of HLA antibodies on survival after transplant and the development of BOS were determined using Cox models.
  
  
  RESULTS
  Of the 441 recipients, 139 (32%) had detectable antibodies to HLA. Of these 139, 54 (39%) developed antibodies specific to donor HLA. The detection of posttransplant HLA antibodies was associated with BOS (HR, 1.54; P=.04) and death (HR, 1.53; P=.02) in multivariable models. The detection of donor-specific HLA antibodies was associated with death (HR, 2.42; P<.0001). The detection of posttransplant HLA antibodies was associated with pretransplant HLA-antibody detection, platelet transfusions, and the development of BOS and cytomegalovirus pneumonitis.
  
  
  CONCLUSIONS
  Approximately one-third of lung transplant recipients have detectable HLA antibodies, which are associated with a worse prognosis regarding graft function and patient survival.
authors: Department of Medicine, Duke University, Durham, NC. Electronic address: laurie.snyder@dm.duke.edu.
authors: Laurie D
authors: LD
authors: Snyder
authors: Department of Medicine, Duke University, Durham, NC.
authors: Ziwei
authors: Z
authors: Wang
authors: Department of Pathology, Duke University, Durham, NC.
authors: Dong-Feng
authors: DF
authors: Chen
authors: Department of Pediatrics and Medical Genetics Research Institute, Cedars-Sinai Health Systems, Los Angeles, CA.
authors: Nancy L
authors: NL
authors: Reinsmoen
authors: Department of Medicine, Duke University, Durham, NC.
authors: C Ashley
authors: CA
authors: Finlen-Copeland
authors: Department of Medicine, Duke University, Durham, NC.
authors: W Austin
authors: WA
authors: Davis
authors: Department of Medicine, Duke University, Durham, NC.
authors: David W
authors: DW
authors: Zaas
authors: Department of Medicine, Duke University, Durham, NC.
authors: Scott M
authors: SM
authors: Palmer
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001989:Bronchiolitis Obliterans / Q000453:epidemiology* / Q000401:mortality*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D000906:Antibodies; D015415:Biomarkers; D006680:HLA Antigens