title: Intact HLA not beta2m-free heavy chain-specific HLA class I antibodies are predictive of graft failure.
abstract: BACKGROUND
  We investigated the effects of intact and beta2m-free heavy chain (HC)-specific human leukocyte antigen (HLA) class I antibodies on long-term graft survival.
  
  
  METHODS
  HLA class I mixed antigen beads were used to detect intact and beta2m-free HC-specific antibodies, whereas elution buffer-treated beads were used to detect antibodies against beta2m-free HC. Donor-specific antibodies (DSAs) were identified using single-antigen beads. Complement-dependent cytotoxicity assays were performed to determine the cytotoxicity of DSA.
  
  
  RESULTS
  Three hundred seventy-nine of 994 of patients (38%) had antibodies against intact HLA and beta2m-free HC. There was no survival rate difference between antibody-positive and -negative groups. When the 379 antibody-positive patients were further tested with beta2m-free HC-coated beads, 179 of them with antibodies only against intact form of antigens had a 4-year graft survival rate of 76%, which is significantly lower than that of 200 patients with antibodies against beta2m-free HC of HLA antigens (88%, P=0.0056). Patients with intact antigen specific DSAs had a significantly lower graft survival rate as compared with those with no DSAs (70% vs. 89%, P=0.0073). More patients with strong donor-specific cytotoxic antibodies lost allografts than those with weak-cytotoxic or noncytotoxic antibodies. However, cytotoxic activity of DSA was not correlated to antibody level.
  
  
  CONCLUSIONS
  We concluded that intact antigen-specific antibodies, especially DSAs, are predictive of graft failure. DSAs were not always cytotoxic. Strong cytotoxic activity of DSA was associated with a higher rate of graft loss but not correlated to the antibody level. Antibodies against beta2m-free HC negatively interfere with the predictive value of intact antigen-specific antibodies.
authors.affiliation: Terasaki Foundation Laboratory, Los Angeles, CA, USA. terasaki@terasakilab.org
authors.forename: Junchao
authors.initials: J
authors.lastname: Cai
authors.forename: Paul I
authors.initials: PI
authors.lastname: Terasaki
authors.forename: Naomi
authors.initials: N
authors.lastname: Anderson
authors.forename: Nils
authors.initials: N
authors.lastname: Lachmann
authors.forename: Constanze
authors.initials: C
authors.lastname: Schönemann
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D007518:Isoantibodies / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D014184:Transplantation, Homologous / Q000276:immunology; D017211:Treatment Failure
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D007143:Immunoglobulin Heavy Chains; D007518:Isoantibodies