Endothelial Protein C Receptor Is Upregulated during Acute and Chronic Antibody-Mediated Rejection in Renal Allografts
Thuy Nguyen, Gabrielle Rizzuto, Kuang-Yu Jen, Zoltan Laszik. University of California San Francisco, San Francisco, CA
Background: Endothelial protein C receptor (EPCR) plays an active role in both pro-inflammatory and anti-inflammatory signaling mostly via protease activated receptors. Since endothelial cells are the primary target of antibody-mediated rejection (AMR), changes in endothelial expression of EPCR during AMR may have potential diagnostic and therapeutic utility. The aim of this study was to assess the endothelial expression of EPCR in acute and chronic antibody-mediated rejection in allograft kidneys.
Design: The study included renal transplant biopsies with acute AMR (n=6) (diffusely C4d positive) and chronic AMR with transplant glomerulopathy (n=6, diffusely C4d positive; n=7, C4d negative). Control cases included protocol biopsies 6 month post transplantation without any pathologic changes (n=10). Double immunofluorescence stains for CD34 and EPCR were performed on paraffin-embedded tissue. Co-expression of EPCR with CD34 in the renal cortex was assessed using computer assisted morphometric analysis.
Results: Expression of EPCR in the protocol biopsies was limited to the endothelial cells of large arteries and veins. EPCR expression was up-regulated in the tubulointerstitial capillaries of all three study groups including C4d negative chronic AMR (p<0.0008). There were no significant differences in endothelial EPCR expression between cases with C4d positive and C4d negative chronic AMR.
Conclusions: Up-regulation of EPCR in the tubulointerstitial capillaries during AMR may provide an additional marker to aid the morphologic diagnosis of various forms of AMR. Given the prominent role of EPCR in various signaling pathways, the possibility of EPCR as a therapeutic target should also be considered.
Category: Kidney (does not include tumors)
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 291, Wednesday Afternoon