title: Anti-Angiotensin II Type 1 Receptor and Anti-Endothelial Cell Antibodies: A Cross-Sectional Analysis of Pathological Findings in Allograft Biopsies.
abstract: 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).
  
  
  
  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.
  
  
  
  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).
  
  
  
  The data show an association between non-HLA antibodies detected in the ECXM and AT1R ELISA and microvascular injury observed in antibody mediated rejection.
authors.affiliation: 1 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. 2 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD. 3 Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD. 4 Clinic of Nephrology and Intensive Care Medicine Campus Virchow-Klinikum and Center for Cardiovascular Research, Medical Faculty of the Charite, Berlin, Germany.
authors.forename: Mary Carmelle
authors.initials: MC
authors.lastname: Philogene
authors.forename: Serena
authors.initials: S
authors.lastname: Bagnasco
authors.forename: Edward S
authors.initials: ES
authors.lastname: Kraus
authors.forename: Robert A
authors.initials: RA
authors.lastname: Montgomery
authors.forename: Duska
authors.initials: D
authors.lastname: Dragun
authors.forename: Mary S
authors.initials: MS
authors.lastname: Leffell
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Zachary
authors.forename: Annette M
authors.initials: AM
authors.lastname: Jackson
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D001323:Autoantibodies / Q000032:analysis*; D001706:Biopsy; D003430:Cross-Sectional Studies; D042783:Endothelial Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000032:analysis; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: C544065:AGTR1 protein, human; D001323:Autoantibodies; D006680:HLA Antigens; D007518:Isoantibodies; D044140:Receptor, Angiotensin, Type 1