title: Formation of donor-specific human leukocyte antigen antibodies after kidney transplantation: correlation with acute rejection and tapering of immunosuppression.
abstract: BACKGROUND
  Before kidney transplantation, a serological crossmatch is routinely performed between donor and recipient to prevent hyperacute rejection by donor-specific anti-human leukocyte antigen (HLA) antibodies. After transplantation, the presence of these antibodies is not routinely monitored. We wanted to know whether donor-specific anti-HLA antibodies are detectable during acute rejection (AR), before or after reduction of immunosuppression in kidney transplant recipients who were converted from cyclosporine A (CsA) to the less nephrotoxic azathioprine (AZA) or mycophenolate mofetil (MMF) at 1 year after transplantation.
  
  
  METHODS
  Plasma samples were collected before transplantation, at several time points after transplantation, and during AR. Antibodies were measured in 29 patients: 5 patients with AR during the first year after transplantation (before conversion), 14 patients with AR after conversion or dose-reduction of AZA or MMF, and a control group of 10 patients without AR during a follow-up of 2 years (1 year before and 1 year after conversion of immunosuppression). Antibodies were measured by complement-dependent cytotoxicity assay, enzyme-linked immunosorbent assay (ELISA), and flow-cytometry in a crossmatch with donor spleen cells.
  
  
  RESULTS
  Donor-specific antibodies were not detectable after transplantation in the control group without AR, nor in patients with AR shortly after transplantation during CsA therapy. After conversion from CsA to AZA or MMF, antibodies appeared only in one patient after graft failure followed by transplantectomy and in patients during AR on AZA but not on MMF therapy.
  
  
  CONCLUSIONS
  In this patient group, we could not detect donor-specific antibodies during CsA treatment, not even at the time of AR using three different techniques. Donor-specific antibodies were primarily present during AR in patients converted from CsA to AZA and were not found in the sera from patients converted to MMF.
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. b.vandermast@erasmusmc.nl.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: van der Mast
authors.forename: Nicole M
authors.initials: NM
authors.lastname: van Besouw
authors.forename: Marian D
authors.initials: MD
authors.lastname: Witvliet
authors.forename: Petronella
authors.initials: P
authors.lastname: de Kuiper
authors.forename: Peter
authors.initials: P
authors.lastname: Smak Gregoor
authors.forename: Teun
authors.initials: T
authors.lastname: van Gelder
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000032:analysis; D001379:Azathioprine / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000276:immunology; D016572:Cyclosporine / Q000008:administration & dosage; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001323:Autoantibodies; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D001379:Azathioprine