title: Late antibody-mediated rejection after heart transplantation following the development of de novo donor-specific human leukocyte antigen antibody.
abstract: BACKGROUND
  Antibody-mediated rejection (AMR) is an important problem after heart transplantation. Most cases seem to occur in sensitized recipients with preformed donor-specific human leukocyte antigen antibody (DSA) early after transplantation. Few data exist on AMR in patients who form de novo DSA. We describe the clinical features and treatment outcome for late AMR secondary to de novo DSA.
  
  
  METHODS
  This was a retrospective, observational cohort study. All heart transplant patients treated for symptomatic AMR secondary to de novo DSA between November 2005 and August 2011.
  
  
  RESULTS
  Fifteen patients were treated for AMR giving an incidence of 3.1 cases per 1000 person years and a prevalence of 1.4%. All had evidence of heart failure on presentation and de novo DSA at diagnosis. There was a spectrum of histologic and immunohistochemical findings. Despite treatment with immunepheresis, intravenous immunoglobulin, and rituximab, and in some cases total lymph node irradiation (n=3) and bortezomib (n=2), clinical outcomes were poor. DSA antibody levels, measured using Labscreen single antigen kits, were reduced by a mean of 76% with a median of 77% and a range of 35% to 99%, but were not eliminated. Forty-six percent had persistent cardiac allograft dysfunction. Mean and median survival was 1.3 and 0.8 years after diagnosis of AMR. Only 40% were alive at the end of the study period.
  
  
  CONCLUSIONS
  Late cardiac AMR caused by de novo DSA was an uncommon but serious problem. Despite treatment consistent with current best practice, 46% of patients developed persistent cardiac dysfunction and their medium-term survival was poor.
authors.affiliation: The Royal Brompton and Harefield NHS Foundation Trust, Harefield Hospital, Harefield, Middlesex, UK.
authors.forename: Aidan M
authors.initials: AM
authors.lastname: Hodges
authors.forename: Haifa
authors.initials: H
authors.lastname: Lyster
authors.forename: Anne
authors.initials: A
authors.lastname: McDermott
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Rice
authors.forename: John D
authors.initials: JD
authors.lastname: Smith
authors.forename: Marlene L
authors.initials: ML
authors.lastname: Rose
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Banner
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology* / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000627:therapeutic use; D012189:Retrospective Studies; D000069283:Rituximab; D015996:Survival Rate; D013997:Time Factors; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D058846:Antibodies, Monoclonal, Murine-Derived; D001897:Boronic Acids; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D011719:Pyrazines; D000069283:Rituximab; D000069286:Bortezomib