title: The role of donor-specific antibodies in acute cardiac allograft dysfunction in the absence of cellular rejection.
abstract: BACKGROUND
  Acute allograft dysfunction (AAD) is an important cause of morbidity among heart transplant recipients. The role of donor-specific antibodies (DSAs) in AAD, with the increasing use of single antigen bead (SAB) assays that have improved the ability to detect DSA, remains unclear.
  
  
  METHODS
  We retrospectively reviewed 329 heart transplant recipients followed up at our institution. AAD was defined as an acute decline in left ventricular ejection fraction to less than 50% and a decrement of 10% or higher compared to baseline in the absence of cellular rejection. Patients with AAD were compared with matched 30 heart transplant controls.
  
  
  RESULTS
  There were 10 (3%) patients with AAD, 4 (40%) had DSA detectable by SAB assay compared to 16 (53%) controls (P=0.43). Peak DSA mean fluorescent intensity (MFI) levels were significantly higher at baseline (class I and class II) in AAD compared to controls. DSA MFI values increased at the time of AAD and returned to baseline values during follow-up for these patients with AAD (P<0.05) but remained unchanged over time for controls. Six (60%) patients with AAD and 1 (3%) control had antibody-mediated rejection (AMR) by endomyocardial biopsy (P<0.01). There were 4 (40%) patients with AAD with no DSA or AMR.
  
  
  CONCLUSIONS
  AAD after heart transplant is a heterogeneous process characterized by 1) AMR and DSA, 2) AMR but no DSA, and 3) no AMR or DSA. The presence of DSA is not associated with AAD, but the quantity assessed by MFI levels may play a role.
authors.affiliation: 1 Division of Cardiovascular Diseases, Department of Medicine, William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN. 2 Division of Cardiovascular Surgery, Department of Surgery, William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN. 3 Department of Laboratory Medicine and Pathology, William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN. 4 Address correspondence to: Naveen L. Pereira, M.D., Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55901.
authors.forename: Nowell M
authors.initials: NM
authors.lastname: Fine
authors.forename: Richard C
authors.initials: RC
authors.lastname: Daly
authors.forename: Nisha
authors.initials: N
authors.lastname: Shankar
authors.forename: Soon J
authors.initials: SJ
authors.lastname: Park
authors.forename: Sudhir S
authors.initials: SS
authors.lastname: Kushwaha
authors.forename: Manish J
authors.initials: MJ
authors.lastname: Gandhi
authors.forename: Naveen L
authors.initials: NL
authors.lastname: Pereira
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D064591:Allografts; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D017023:Coronary Angiography; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000517:prevention & control; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008910:Minnesota; D012189:Retrospective Studies; D013318:Stroke Volume; D013997:Time Factors; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D007518:Isoantibodies