Renal and Urinary Levels of Endothelial Protein C Receptor Correlate with Acute Renal Allograft Rejection

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 c...

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Published in:PloS one Vol. 8; no. 5; p. e64994
Main Authors: Lattenist, Lionel, Kers, Jesper, Claessen, Nike, ten Berge, Ineke J. M., Bemelman, Frederike J., Florquin, Sandrine, Roelofs, Joris J. T. H.
Format: Journal Article
Language:English
Published: United States Public Library of Science 22.05.2013
Public Library of Science (PLoS)
Subjects:
Activation
Adult
Aged
Allografts
Antibodies
Anticoagulants
Antigens, CD - genetics
Antigens, CD - metabolism
Antigens, CD - urine
Arteries
Biology
Biomarkers
Biomarkers - metabolism
Biomarkers - urine
Biopsy
Blood vessels
Capillaries
Coagulation
Cohort Studies
Endothelial Protein C Receptor
Endothelium
Enzyme-linked immunosorbent assay
Female
Gene expression
Graft Rejection
Humans
Inflammation
Kidney Transplantation
Leukocytes
Lymphocytes T
Male
Medicine
Middle Aged
mRNA
Multivariate analysis
Nephrology
Pathology
Patients
Polymerase chain reaction
Proteases
Protein C
Proteins
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
Rejection
RNA
RNA, Messenger - genetics
ROC Curve
Rodents
Sepsis
T cells
Transplantation
Transplants & implants
Tubules
Urine
Young Adult
Netherlands
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary: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.
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Conceived and designed the experiments: LL JJTHR. Performed the experiments: LL. Analyzed the data: LL JK JJTHR. Contributed reagents/materials/analysis tools: JK NC IJMtB FJB. Wrote the paper: LL JK JJTHR. Corrected the manuscript: JK JJTHR SF.
Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0064994