title: Donor-specific anti-HLA antibodies with antibody-mediated rejection and long-term outcomes following heart transplantation.
abstract: BACKGROUND
  Donor-specific anti-HLA antibodies (DSA) are common after heart transplantation and are associated with rejection, cardiac allograft vasculopathy, and mortality. A noninvasive diagnostic test for pathologic antibody-mediated rejection (pAMR) does not exist.
  
  
  METHODS
  From January 1, 2010, through August 31, 2013, 221 consecutive adult patients underwent heart transplantation and were followed through October 1, 2015. The primary objective was to determine whether the presence of DSA could detect AMR at the time of pathologic diagnosis. Secondary analyses included association of DSA (stratified by major histocompatibility complex class and de novo status) during AMR with new graft dysfunction, graft loss (mortality or retransplantation), and development of cardiac allograft vasculopathy.
  
  
  RESULTS
  During the study period, 69 patients (31.2%) had DSA (24% had de novo DSA), and there were 74 episodes of pAMR in 38 patients. Sensitivity of DSA at any mean fluorescence intensity to detect concurrent pAMR was only 54.3%. The presence of any DSA during pAMR increased the odds of graft dysfunction (odds ratio = 5.37; 95% confidence interval [CI], 1.34-21.47; p = 0.018), adjusting for age, sex, and timing of AMR. Circulating class II DSA after transplantation increased risk of future pAMR (hazard ratio = 2.97; 95% CI, 1.31-6.73; p = 0.009). Patients who developed de novo class II DSA had 151% increased risk of graft loss (contingent on 30-day survival) compared with patients who did not have DSA (95% CI, 1.11-5.69; p = 0.027).
  
  
  CONCLUSIONS
  DSA were inadequate to diagnose pAMR. Class II DSA provided prognostic information regarding future pAMR, graft dysfunction with pAMR, and graft loss.
authors.affiliation: Department of Medicine, Division of Cardiology, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Clerkin
authors.affiliation: Department of Medicine, Division of Cardiology, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Maryjane A
authors.initials: MA
authors.lastname: Farr
authors.affiliation: Department of Medicine, Division of Cardiology, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Susan W
authors.initials: SW
authors.lastname: Restaino
authors.affiliation: Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Zorn
authors.affiliation: Department of Medicine, Division of Cardiology, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Farhana
authors.initials: F
authors.lastname: Latif
authors.affiliation: Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Elena R
authors.initials: ER
authors.lastname: Vasilescu
authors.affiliation: Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Marboe
authors.affiliation: Department of Medicine, Division of Cardiology, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Paolo C
authors.initials: PC
authors.lastname: Colombo
authors.affiliation: Department of Medicine, Division of Cardiology, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: donna.mancini@mountsinai.org.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Mancini
mesh_terms: D000328:Adult; D064591:Allografts / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D016027:Heart Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012086:Reoperation; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D014019:Tissue Donors; D014181:Transplantation Immunology / Q000502:physiology*; D014481:United States
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies
keywords: antibody mediated rejection; cardiac allograft vasculopathy; donor specific antibodies; heart transplant; mortality