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Anti-Angiotensin II Type 1 Receptor and Anti-Endothelial Cell Antibodies: A
Cross-Sectional Analysis of Pathological Findings in Allograft Biopsies
#MMPMID27222934
Philogene MC
; Bagnasco S
; Kraus ES
; Montgomery RA
; Dragun D
; Leffell MS
; Zachary AA
; Jackson AM
Transplantation
2017[Mar]; 101
(3
): 608-615
PMID27222934
show ga
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.