Expression of endothelial protein C receptor in cortical peritubular capillaries associates with a poor clinical response in lupus nephritis.
OBJECTIVE
To study the membrane expression of endothelial protein C receptor (mEPCR) in the renal microvasculature in lupus nephritis (LN) as a potential marker of injury and/or prognostic indicator for response to therapy.


METHODS
mEPCR expression was analysed by immunohistochemistry in normal kidney and in 59 biopsies from 49 patients with LN. Clinical parameters were assessed at baseline, 6 months and 1 year.


RESULTS
mEPCR was expressed in the medulla, arterial endothelium and cortical peritubular capillaries (PTCs) in all biopsies with LN but not in the cortical PTCs of normal kidney. Positive mEPCR staining in >25% of the PTCs was observed in 16/59 biopsies and associated with poor response to therapy. Eleven (84.6%) of 13 patients with positive staining for mEPCR in >25% of the PTCs and follow-up at 6 months did not respond to therapy, compared with 8/28 (28.6%) with mEPCR staining in < or =25% PTCs, P = 0.0018. At 1 year, 10 (83.3%) of 12 patients with positive mEPCR staining in >25% of the PTCs did not respond to therapy (with two progressing to end-stage renal disease) compared with 8/24 (33.3%) with positive staining in < or =25% of the PTCs, P = 0.0116. Although tubulo-interstitial damage (TID) was always accompanied by mEPCR, this endothelial marker was extensively expressed in the absence of TID suggesting that poor response could not be attributed solely to increased TID. mEPCR expression was independent of International Society of Nephrology/Renal Pathology Society class, activity and chronicity indices.


CONCLUSIONS
Increased mEPCR expression in PTCs may represent a novel marker of poor response to therapy for LN.
Izmirly
Peter M
PM
Department of Medicine, Division of Rheumatology, New York University School of Medicine, NY, USA. izmirp01@nyumc.org
Barisoni
Laura
L
Buyon
Jill P
JP
Kim
Mimi Y
MY
Rivera
Tania L
TL
Schwartzman
Julie S
JS
Weisstuch
Joseph M
JM
Liu
David T
DT
Bernstein
Stephen
S
Tseng
Chung-E
CE
Belmont
Howard M
HM
Esmon
Charles T
CT
Merrill
Joan T
JT
Askanase
Anca D
AD
Thomas
David B
DB
Clancy
Robert M
RM
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D000074283:Endothelial Protein C Receptor; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007672:Kidney Cortex / Q000098:blood supply* / Q000473:pathology; D008181:Lupus Nephritis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016896:Treatment Outcome; D055815:Young Adult
D015703:Antigens, CD; D015415:Biomarkers; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D011956:Receptors, Cell Surface