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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

Philogene, Mary Carmelle PhD; Bagnasco, Serena MD; Kraus, Edward S. MD; Montgomery, Robert A. MD, DPhil; Dragun, Duska MD; Leffell, Mary S. PhD; Zachary, Andrea A. PhD; Jackson, Annette M. PhD

doi: 10.1097/TP.0000000000001231
Original Clinical Science—General

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.

The histologic characteristics of kidney graft injury are examined in terms of the presence of anti-angiotensin II type 1 receptor antibody (AT1R-Ab) and anti-endothelial cell antibody (AECA). The presence of AECA or AT1R-Ab correlates with microvascular injury observed in antibody-mediated rejection.

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.

Received 19 November 2015. Revision received 18 February 2016.

Accepted 8 March 2016.

The authors declare no funding or conflicts of interest.

M.C. Philogene participated in the design, data analysis, and writing of the manuscript. S. Bagnasco participated in the design, data analysis, and writing of the manuscript. E. Kraus participated in the writing of the manuscript. R.A. Montgomery participated in the writing of the manuscript. D.D. participated in the data analysis. M.S. Leffell participated in the data analysis and writing of the manuscript. A.A. Zachary participated in the data analysis and writing of the manuscript. A.M. Jackson participated in the design, data analysis, and writing of the manuscript.

Correspondence: Mary Carmelle Philogene, PhD, Immunogenetics Laboratory, 2041 E. Monument Street, Baltimore, MD 21205. (mphilogene@jhmi.edu).

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