The influence of non-HLA antibodies directed against angiotensin II type 1 receptor (AT1R) on early renal transplant outcomes

Transpl Int. 2014 Oct;27(10):1029-38. doi: 10.1111/tri.12371. Epub 2014 Jun 30.

Abstract

Non-HLA antibodies (Abs) targeting vascular receptors are thought to have an impact on renal transplant injury. Anti-angiotensin II type 1-receptor-activating antibodies (anti-AT1R) have been mentioned to stimulate a severe vascular rejection, but the pretransplant screening has not been introduced yet. The aim of our study was to assess the incidence and importance of anti-AT1R antibodies and their influence on renal transplant in the 1st year of observation. We prospectively evaluated the presence of anti-AT1R antibodies in 117 consecutive renal transplant recipients in pre- and post-transplant screening. Anti-AT1R antibodies were observed in 27/117 (23%) of the analyzed recipients already before transplantation. The function of renal transplant was considerably worse in anti-AT1R(+) group. The patients with anti-AT1R Abs >9 U/ml lost their graft more often. Biopsy-proven AR was described in 4/27 (15%) pts in the anti-AT1R(+) group and 13/90 (14.4%) in the anti-AT1R(-) group, but more severe cases of Banff IIB or antibody-mediated rejection (AMR) were more often observed in anti-AT1R (+) 4/27 (15%) vs. 1/90 (1.1%) in anti-AT1R(+) (P = 0.009). Patients with anti-AT1R Abs level >9 U/ml run a higher risk of graft failure independently of classical immunological risk factors. The recipients with anti-AT1R Abs developed more severe acute rejections described as IIB or AMR in Banff classification. More recipients among the anti-AT1R-positive ones lost the graft. Our study suggests monitoring of anti-AT1R Abs before renal transplantation for assessment of immunologic risk profiles and the identification of patients highly susceptible to immunologic events, graft failure, and graft loss.

Keywords: angiotensin II type 1 receptor antibodies; antibody-mediated rejection; humoral rejection; non-HLA antibodies; renal transplant injury; renal transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / immunology*
  • Autoantibodies / metabolism
  • Biomarkers / analysis
  • Cohort Studies
  • Confidence Intervals
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Graft Rejection / immunology*
  • HLA Antigens / immunology*
  • HLA Antigens / metabolism
  • Humans
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / methods*
  • Male
  • Middle Aged
  • Odds Ratio
  • Preoperative Care / methods
  • Prospective Studies
  • Receptor, Angiotensin, Type 1 / immunology*
  • Receptor, Angiotensin, Type 1 / metabolism
  • Sensitivity and Specificity
  • Transplantation Immunology / immunology

Substances

  • Autoantibodies
  • Biomarkers
  • HLA Antigens
  • Receptor, Angiotensin, Type 1