title: Renal and urinary levels of endothelial protein C receptor correlate with acute renal allograft rejection.
abstract: The Endothelial Protein C Receptor (EPCR) is expressed on leukocytes, on endothelium of large blood vessels and to a lesser extent on capillaries. Membrane bound EPCR plays an important role in the activation of protein C which has anticoagulant, anti-inflammatory and cytoprotective effects. After cleavage by a protease EPCR is also found as a soluble protein. Acute rejection of kidney allografts can be divided in T-cell-mediated rejection (TCMR) and antibody-mediated (ABMR) rejection. The latter is characterized by strong activation of coagulation. Currently no reliable non-invasive biomarkers are available to monitor rejection. Renal biopsies were available from 81 renal transplant patients (33 without rejection, 26 TCMR and 22 ABMR), we had access to mRNA material, matched plasma and urine samples for a portion of this cohort. Renal EPCR expression was assessed by RT-PCR and immunostaining. Plasma and urine sEPCR levels were measured by ELISA. ABMR patients showed higher levels of EPCR mRNA than TCMR patients. EPCR expression on glomeruli was significantly elevated in ABMR patients than in TCMR or control patients. In the peritubular capillaries EPCR expression was higher in ABMR patients than in control patients. EPCR expression was higher in tubules and arteries of rejection patients than in control patients. Plasma sEPCR levels did not differ. Urine sEPCR levels were more elevated in the ABMR group than in patients with TCMR or without rejection. ROC analysis demonstrated that urinary sEPCR is appropriate to discriminate between ABMR patients and TCMR or control patients. We conclude that urinary sEPCR could be a novel non-invasive biomarker of antibody mediated rejection in renal transplantation.
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. l.c.lattenist@amc.uva.nl
authors.forename: Lionel
authors.initials: L
authors.lastname: Lattenist
authors.forename: Jesper
authors.initials: J
authors.lastname: Kers
authors.forename: Nike
authors.initials: N
authors.lastname: Claessen
authors.forename: Ineke J M
authors.initials: IJ
authors.lastname: ten Berge
authors.forename: Frederike J
authors.initials: FJ
authors.lastname: Bemelman
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Joris J T H
authors.initials: JJ
authors.lastname: Roelofs
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D015415:Biomarkers / Q000378:metabolism* / Q000652:urine; D001706:Biopsy; D015331:Cohort Studies; D000074283:Endothelial Protein C Receptor; D005260:Female; D006084:Graft Rejection; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D012372:ROC Curve; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface