Expression of endothelial protein C receptor in cortical peritubular capillaries associates with a poor clinical response in lupus nephritis

Peter M. Izmirly, Laura Barisoni, Jill P. Buyon, Mimi Kim, Tania L. Rivera, Julie S. Schwartzman, Joseph M. Weisstuch, David T. Liu, Stephen Bernstein, Chung E. Tseng, Howard M. Belmont, Charles T. Esmon, Joan T. Merrill, Anca D. Askanase, David B. Thomas, Robert M. Clancy

Research output: Contribution to journalArticle

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Abstract

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 anovel marker of poor response to therapy for LN.

Original languageEnglish (US)
Pages (from-to)513-519
Number of pages7
JournalRheumatology
Volume48
Issue number5
DOIs
StatePublished - 2009

Fingerprint

Lupus Nephritis
Protein C
Membranes
Staining and Labeling
Kidney
Biopsy
Therapeutics
Microvessels
Chronic Kidney Failure
Endothelium
Immunohistochemistry
Pathology

Keywords

  • Endothelial protein C receptor
  • Lupus nephritis
  • Lupus nephritis pathological biomarker
  • Renal microvasculature in lupus nephritis

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

Cite this

Expression of endothelial protein C receptor in cortical peritubular capillaries associates with a poor clinical response in lupus nephritis. / Izmirly, Peter M.; Barisoni, Laura; Buyon, Jill P.; Kim, Mimi; Rivera, Tania L.; Schwartzman, Julie S.; Weisstuch, Joseph M.; Liu, David T.; Bernstein, Stephen; Tseng, Chung E.; Belmont, Howard M.; Esmon, Charles T.; Merrill, Joan T.; Askanase, Anca D.; Thomas, David B.; Clancy, Robert M.

In: Rheumatology, Vol. 48, No. 5, 2009, p. 513-519.

Research output: Contribution to journalArticle

Izmirly, PM, Barisoni, L, Buyon, JP, Kim, M, Rivera, TL, Schwartzman, JS, Weisstuch, JM, Liu, DT, Bernstein, S, Tseng, CE, Belmont, HM, Esmon, CT, Merrill, JT, Askanase, AD, Thomas, DB & Clancy, RM 2009, 'Expression of endothelial protein C receptor in cortical peritubular capillaries associates with a poor clinical response in lupus nephritis', Rheumatology, vol. 48, no. 5, pp. 513-519. https://doi.org/10.1093/rheumatology/kep034
Izmirly, Peter M. ; Barisoni, Laura ; Buyon, Jill P. ; Kim, Mimi ; Rivera, Tania L. ; Schwartzman, Julie S. ; Weisstuch, Joseph M. ; Liu, David T. ; Bernstein, Stephen ; Tseng, Chung E. ; Belmont, Howard M. ; Esmon, Charles T. ; Merrill, Joan T. ; Askanase, Anca D. ; Thomas, David B. ; Clancy, Robert M. / Expression of endothelial protein C receptor in cortical peritubular capillaries associates with a poor clinical response in lupus nephritis. In: Rheumatology. 2009 ; Vol. 48, No. 5. pp. 513-519.
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abstract = "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 anovel marker of poor response to therapy for LN.",
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T1 - Expression of endothelial protein C receptor in cortical peritubular capillaries associates with a poor clinical response in lupus nephritis

AU - Izmirly, Peter M.

AU - Barisoni, Laura

AU - Buyon, Jill P.

AU - Kim, Mimi

AU - Rivera, Tania L.

AU - Schwartzman, Julie S.

AU - Weisstuch, Joseph M.

AU - Liu, David T.

AU - Bernstein, Stephen

AU - Tseng, Chung E.

AU - Belmont, Howard M.

AU - Esmon, Charles T.

AU - Merrill, Joan T.

AU - Askanase, Anca D.

AU - Thomas, David B.

AU - Clancy, Robert M.

PY - 2009

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N2 - 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 anovel marker of poor response to therapy for LN.

AB - 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 anovel marker of poor response to therapy for LN.

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KW - Renal microvasculature in lupus nephritis

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