title: Effect of pretransplant human leukocyte antigen antibodies detected by solid-phase assay on heart transplant outcomes.
abstract: BACKGROUND
  The significance of pretransplant human leukocyte antigen antibodies (HLA-Abs), especially donor-specific HLA-Abs (DSA), as detected by single antigen bead assay (SAB), is not well characterized in cardiac transplantation (CTX). We analyzed the significance of DSA detected by SAB in predicting crossmatch (XM) results and post-transplant rejection.
  
  
  METHODS
  We performed a retrospective study of 85 CTX with negative cytotoxicity XM. We tested pretransplant sera collected within 24 hours of transplantation by flow cytometric XM (FXM) and SAB. DSA identified by SAB were utilized to perform a virtual crossmatch (VXM). Positive VXM was defined as the presence of DSA at mean fluorescence intensity (DMFI)>1500. Additionally, to analyze the significance of low-level DSA weakly positive VXM was DMFI 300 to 1500. We defined a negative VXM as MFI<300. VXM results were correlated with FXM results and with posttransplant rejection.
  
  
  RESULTS
  Patients in the weakly positive and negative VXM had similar posttransplant rejections. DMFI>1500 correlates well with FXM results (accuracy=90%). Patients with DMFI>1500 had a higher incidence of antibody-medicated rejection (AMR; P=.0052), AMR grade I (P<.0001), cell-mediated rejection (CMR) grade>1R/1A (P=.018), and CMR grade>2R/3A (P=.057). Similarly patients with positive FXM had a higher incidence of AMR (P=.091), AMR grade 1 (P<.0001), CMR grade>1R/1A (P=.05), and CMR grade>2R/3A (P=.56).
  
  
  CONCLUSIONS
  In conclusion, SAB defined DMFI>1500 can be used as a surrogate for FXM. Recipients with DMFI>1500 pretransplant and positive FXM have significantly higher rates of AMR and CMR compared to recipients with DMFI<1500 or negative FXM.
authors.affiliation: Division of Transfusion Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA. gandhi.manish@mayo.edu
authors.forename: M J
authors.initials: MJ
authors.lastname: Gandhi
authors.forename: S R
authors.initials: SR
authors.lastname: DeGoey
authors.forename: K
authors.initials: K
authors.lastname: Bundy
authors.forename: W K
authors.initials: WK
authors.lastname: Kremers
authors.forename: R
authors.initials: R
authors.lastname: Knauer
authors.forename: N
authors.initials: N
authors.lastname: Pereira
authors.forename: B
authors.initials: B
authors.lastname: Edwards
authors.forename: S
authors.initials: S
authors.lastname: Kushwaha
authors.forename: R C
authors.initials: RC
authors.lastname: Daly
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D007163:Immunosorbent Techniques; D007518:Isoantibodies / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D008910:Minnesota; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies