Investigation of Serum Angiotensin II Type 1 Receptor Antibodies at the Time of Renal Allograft Rejection

Ann Lab Med. 2015 May;35(3):314-20. doi: 10.3343/alm.2015.35.3.314. Epub 2015 Apr 1.

Abstract

Background: Angiotensin II type 1 receptor (AT1R) is responsible for cardiovascular effects mediated by angiotensin II. This study aimed to investigate the impact of antibodies directed against AT1R (anti-AT1R) in renal allograft rejection.

Methods: We evaluated 53 patients who had biopsy-proven rejection including antibody-mediated rejection (AMR) (N=22), T-cell-mediated rejection (TCMR) (N=29), and mixed AMR and TCMR (N=2). Donor specific HLA antibodies (DSA) and anti-AT1Rs were simultaneously determined.

Results: Anti-AT1Rs were detected in 9.4% (5/53) of rejection patients (one with acute AMR, two with chronic active AMR, one with acute TCMR, and one with mixed acute AMR & TCMR). HLA antibodies and DSA were detected in 75.5% (40/53) and 49.1% (26/53) of patients, respectively. There was no significant difference in transplant characteristics between anti-AT1R(+) and anti-AT1R(-) patients except for the association of HLA class-I DSA(+) and anti-AT1R(+). Four of five anti-AT1R(+) patients had DSA and were also found to have AMR. A single anti-AT1R(+)/DSA(-) patient developed acute TCMR. Detection rates of DSA, HLA antibodies, or anti-AT1R were not different between AMR and TCMR. However, DSA(+)/anti-AT1R(+) was more frequently found in AMR than in TCMR (P=0.036). Patients with anti-AT1R showed a greater tendency to develop high-grade rejection as Banff IIA/IIB or AMR.

Conclusions: The presence of anti-AT1R was significantly associated with HLA class-I DSA in renal allograft rejection patients. Both anti-AT1R and DSA positivity was associated with AMR in patients with renal allograft rejection.

Keywords: Angiotensin II receptor antibodies; Biopsy; Rejection; Renal transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies / blood
  • Female
  • Graft Rejection / etiology*
  • HLA Antigens / immunology
  • Humans
  • Kidney / pathology
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Receptor, Angiotensin, Type 1 / immunology*
  • Tissue Donors
  • Transplantation, Homologous

Substances

  • Antibodies
  • HLA Antigens
  • Receptor, Angiotensin, Type 1