title: Detection of anti-HLA antibody by flow cytometry in patients with a left ventricular assist device is associated with early rejection following heart transplantation.
abstract: BACKGROUND
  Patients with a left ventricular assist device (LVAD) as a bridge to heart transplantation (HT) often have elevated levels of panel reactive antibodies (PRA). The clinical significance of anti-human histocompatibility leukocyte antigen (HLA) antibodies detected by flow cytometry in PRA negative patients remains unclear.
  
  
  METHODS
  Eighteen patients who underwent LVAD placement as a successful bridge to HT had standard anti-human globulin complement-dependent cytotoxicity and retrospective flow cytometry assays performed to detect class I anti-HLA antibodies. A positive flow result was defined as a fluorescent ratio of 23:1 versus a negative control.
  
  
  RESULTS
  Six patients had anti-HLA antibodies detected by flow cytometry. Univariate analysis demonstrated more moderate-severe rejection episodes (ISHLT > or = IIIA) at 2 months (0.83+/-0.75 vs. 0; P=0.04) and a trend toward decreased time to first rejection (61+/-17 vs. 225+/-62 days; P=0.06) in these patients. No differences were observed in donor-recipient HLA mismatch or 1 year Kaplan-Meier survival between patients with or without anti-HLA antibodies.
  
  
  CONCLUSIONS
  Despite a negative PRA, LVAD patients with class I anti-HLA antibodies detected by flow cytometry have a greater incidence of moderate-severe rejection in the first 2 months after HT. Flow cytometry may be a useful clinical tool in screening PRA negative LVAD patients before transplantation. Patients with positive anti-HLA antibody screening by flow cytometry may require more intensive immunosuppression in the early post-HT period.
authors.affiliation: Department of Medicine, University of Pennsylvania Health System, Philadelphia 19104, USA.
authors.forename: D
authors.initials: D
authors.lastname: DeNofrio
authors.forename: R
authors.initials: R
authors.lastname: Rho
authors.forename: F J
authors.initials: FJ
authors.lastname: Morales
authors.forename: M
authors.initials: M
authors.lastname: Kamoun
authors.forename: J
authors.initials: J
authors.lastname: Kearns
authors.forename: C
authors.initials: C
authors.lastname: Dorozinsky
authors.forename: B R
authors.initials: BR
authors.lastname: Rosengard
authors.forename: M A
authors.initials: MA
authors.lastname: Acker
authors.forename: E
authors.initials: E
authors.lastname: Loh
mesh_terms: D000328:Adult; D000906:Antibodies / Q000032:analysis*; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection; D006680:HLA Antigens / Q000276:immunology*; D016027:Heart Transplantation; D006353:Heart-Assist Devices; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors; D016277:Ventricular Function, Left
chemical_list: D000906:Antibodies; D006680:HLA Antigens