Anti-Angiotensin II Type 1 Receptor and Anti-Endothelial Cell Antibodies: A Cross-Sectional Analysis of Pathological Findings in Allograft Biopsies

Transplantation. 2017 Mar;101(3):608-615. doi: 10.1097/TP.0000000000001231.

Abstract

Background: This is a cross-sectional study designed to evaluate the histologic characteristics of graft injury in the presence of anti-angiotensin II type 1 receptor antibody (AT1R-Ab) and anti-endothelial cell antibody (AECA).

Methods: Non-HLA antibody testing was included in the posttransplant evaluation for 70 kidney recipients. Biopsies were performed for cause for 47 patients and as protocol for the remaining 23 patients. Biopsy-proven rejection was defined according to the Banff 2009-2013 criteria. AT1R-Ab was measured on an ELISA platform. Patients were divided into 3 groups based on AT1R-Ab levels (>17, 10-17, and <10 U/ml). AECA was evaluated using an endothelial cell crossmatch (ECXM) in patients whose HLA antibody level was insufficient to cause a positive flow cytometric crossmatch.

Results: AT1R-Ab levels were higher in patients diagnosed with antibody mediated rejection compared to those with no rejection (P = 0.004). Glomerulitis (g) and peritubular capillaritis (ptc) scores were independently correlated with increased AT1R-Ab concentrations in the presence or absence of HLA-DSA (P = 0.007 and 0.03 for g scores; p = 0.005 and 0.03 for ptc scores). Patients with a positive ECXM had higher AT1R-Ab levels compared to those with a negative ECXM (P = 0.005). Microcirculation inflammation (MCI = g + ptc score) was higher in patients with a positive ECXM and with AT1R-Ab >17 U/ml, although this did not reach statistical significance (P = 0.07).

Conclusions: The data show an association between non-HLA antibodies detected in the ECXM and AT1R ELISA and microvascular injury observed in antibody mediated rejection.

MeSH terms

  • Adult
  • Aged
  • Allografts
  • Autoantibodies / analysis*
  • Biopsy
  • Cross-Sectional Studies
  • Endothelial Cells / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Graft Rejection / diagnosis
  • Graft Rejection / immunology*
  • Graft Rejection / pathology
  • Graft Survival
  • HLA Antigens / immunology
  • Histocompatibility
  • Histocompatibility Testing
  • Humans
  • Isoantibodies / analysis
  • Kidney / immunology*
  • Kidney / pathology
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Receptor, Angiotensin, Type 1 / immunology*
  • Treatment Outcome

Substances

  • AGTR1 protein, human
  • Autoantibodies
  • HLA Antigens
  • Isoantibodies
  • Receptor, Angiotensin, Type 1