title: Clinical implications of angiotensin II type 1 receptor antibodies in antibody-mediated rejection without detectable donor-specific HLA antibodies after renal transplantation.
abstract: BACKGROUND
  Solid-phase immunoassays have improved detection sensitivity for donor-specific HLA antibody (DSHA) and permitted the accurate diagnosis of antibody-mediated rejection (AMR). However, DSHA is not always sufficient to explain the cause of AMR. Consequently, a means of assessing non-HLA antibodies is required to determine the cause of AMR. The aim of the present study was to evaluate the clinical implications of antibodies (Abs) targeting angiotensin II type I receptor (AT1R) in recipients with AMR but without serum DSHA.
  
  
  METHODS
  Non-HLA AMR cases diagnosed between January 2011 and June 2014 were included. Levels of anti-AT1R Abs (U/mL) were quantified by using AT1R assay kits (One Lambda, Calif, United States) with collected sera pretransplantation and at biopsy (cut-off value: 15 U/mL).
  
  
  RESULTS
  Seventy-two patients were diagnosed with AMR during the above-mentioned period. Of them, 12 recipients (16.7%) had no DSHA. The sera of these 12 patients were tested (2 patients were only checked at time of biopsy). Nine patients (9/10) were presensitized for anti-AT1R Abs (median, 25.0 U/mL; range, 12.9 to 50.0 U/mL). Ten patients (10/12) were anti-AT1R- positive at time of biopsy (median, 23.2 U/mL; range, 11.4 to 50.0 U/mL). The mean time from transplantation to biopsy was 73 months. Eight patients experienced acute AMR, and 4 developed chronic AMR. Four patients showed negative C4d staining in peritubular capillaries (4/12). Patients were treated with plasmapheresis, low-dose intravenous immunoglobulin, and/or rituximab.
  
  
  CONCLUSIONS
  AT1R Abs may play a significant role in AMR without detectable DSHA. Pretransplantation detection of AT1R Abs may be helpful for assessing the risk for non-HLA AMR.
authors.affiliation: Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Severance Hospital, Yonsei University Health System, Seoul, Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Severance Hospital, Yonsei University Health System, Seoul, Korea; The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: B S
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Korea.
authors.forename: J G
authors.initials: JG
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Severance Hospital, Yonsei University Health System, Seoul, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Korea; The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Y S
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Korea; The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea. Electronic address: khhuh@yuhs.ac.
authors.forename: K H
authors.initials: KH
authors.lastname: Huh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000276:immunology*; D006680:HLA Antigens / Q000097:blood / Q000276:immunology*; D006801:Humans; D007118:Immunoassay; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D044140:Receptor, Angiotensin, Type 1 / Q000097:blood / Q000276:immunology*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D007518:Isoantibodies; D044140:Receptor, Angiotensin, Type 1