Rheumatology Advance Access originally published online on March 13, 2009
Rheumatology 2009 48(5):513-519; doi:10.1093/rheumatology/kep034
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Expression of endothelial protein C receptor in cortical peritubular capillaries associates with a poor clinical response in lupus nephritis
1Department of Medicine, Division of Rheumatology2Department of Medicine, Division of Nephrology3Department of Pathology, New York University School of Medicine4Department of Epidemiology and Population Health, Division of Biostatistics5Department of Medicine, Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY6The Howard Hughes Medical Institute and Cardiovascular Biology Research Program, Department of Pathology and Department of Biochemistry & Molecular Biology7Clinical Pharmacology Research Program, Department of Medicine and School of Pharmacy, Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, Oklahoma City, OK8Nephrocor, Uniondale, NY, USA.
Correspondence to: Peter M. Izmirly, 560 First Avenue, TCH-407 New York, NY 10016, USA. E-mail: izmirp01{at}nyumc.org
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Abstract |
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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 
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 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.
Conclusion. Increased mEPCR expression in PTCs may represent a novel marker of poor response to therapy for LN.
KEY WORDS: Endothelial protein C receptor, Lupus nephritis, Lupus nephritis pathological biomarker, Renal microvasculature in lupus nephritis
*Peter M. Izmirly and Laura Barisoni equally contributed to this work.
Submitted 9 September 2008;
revised version accepted 26 January 2009.
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