title: Increased negative impact of donor HLA-specific together with non-HLA-specific antibodies on graft outcome.
abstract: BACKGROUND
  De novo donor HLA-specific (dnDSA) and non-HLA antibodies including antiangiotensin type 1 receptor antibodies (AT1R-abs) have been associated with antibody-mediated rejection (AMR) and decreased graft survival as well as cellular-mediated rejection (CMR) and early onset of microvasculopathy in heart transplantation. The aim of our study was to determine the impact of anti-AT1R-ab and anti-donor HLA-specific antibody (DSA) on clinical outcomes.
  
  
  METHODS
  Pretransplant and posttransplant sera from 200 recipients transplanted between May 2007 and August 2011 were tested for DSA (Luminex-based single antigen bead assay) and AT1R-ab (enzyme-linked immunosorbent assay). Two cutoff levels (≥ 17 and ≥ 12 units) were used to define high and intermediate binding of AT1R-ab. Clinical parameters examined were 5-year AMR/CMR (≥ grade 2), coronary artery vasculopathy, and survival.
  
  
  RESULTS
  At 2 years after transplant, freedom from AMR and/or CMR was 95.4% for those with no DSA (n=175), 66.9% for those with dnDSA (n=19), and 25% for those with DSA at transplant (n=6) (P<0.0001). Neither ≥ 17 nor ≥ 12 units of pretransplant levels indicated a significant difference in freedom from AMR and/or CMR. When both dnDSA and AT1R-ab ≥ 17 or ≥ 12 units were considered, freedom from AMR and/or CMR decreased to 50% and 45% (P<0.0001), respectively. Coronary artery vasculopathy and survival were not significantly impacted.
  
  
  CONCLUSIONS
  These results show the increased negative impact of dnDSA and AT1R-ab on freedom from AMR and/or CMR and an increased hazard ratio when both parameters are considered. Both HLA- and non-HLA-specific antibodies seem to impact graft outcome in heart transplantation.
authors.affiliation: 1 HLA Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA. 2 Biostatistics Core, Research Institute and General Clinical Research Center and Cardiothoracic Surgery, Cedars-Sinai Medical Center, Los Angeles, CA. 3 MD Anderson Medical Center, Houston, TX. 4 Pathology, Cedars-Sinai Medical Center, Los Angeles, CA. 5 Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA. 6 Address correspondence to: Nancy L. Reinsmoen, Ph.D., D(ABHI) HLA Laboratory, Cedars-Sinai Medical Center, 8723 Alden Dr, SSB # 197, Los Angeles, CA 90048.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Reinsmoen
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lai
authors.forename: James
authors.initials: J
authors.lastname: Mirocha
authors.forename: Kai
authors.initials: K
authors.lastname: Cao
authors.forename: Geraldine
authors.initials: G
authors.lastname: Ong
authors.forename: Mehrnoush
authors.initials: M
authors.lastname: Naim
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Mark
authors.initials: M
authors.lastname: Haas
authors.forename: Matthew
authors.initials: M
authors.lastname: Rafiei
authors.forename: Lawrence
authors.initials: L
authors.lastname: Czer
authors.forename: Jignesh
authors.initials: J
authors.lastname: Patel
authors.forename: Jon
authors.initials: J
authors.lastname: Kobashigawa
mesh_terms: D000906:Antibodies / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D016027:Heart Transplantation; D006648:Histocompatibility / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D015994:Incidence; D053208:Kaplan-Meier Estimate; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D012189:Retrospective Studies; D014019:Tissue Donors; D014180:Transplantation
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D044140:Receptor, Angiotensin, Type 1