Dysregulation of the microvasculature in nonlesional non-sun-exposed skin of patients with lupus nephritis

Peter M. Izmirly, Marianna Shvartsbeyn, Shane Meehan, Andrew Franks, Alan Braun, Ellen Ginzler, Sherry X. Xu, Herman Yee, Tania Rivera, Charles Esmon, Laura Barisoni-Thomas, Joan T. Merrill, Jill P. Buyon, Robert M. Clancy

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective. Membrane endothelial protein C receptor (mEPCR) is highly expressed in peritubular capillaries of kidneys from patients with active and poorly responsive lupus nephritis (LN). We investigated the hypothesis that changes in the microvasculature are widespread with extension to the dermal vasculature. Methods. Skin biopsies from uninvolved skin (buttocks) were performed in 27 patients with LN and 5 healthy controls. Sections were stained with specific antibodies reactive with mEPCR, adiponectin, intercellular adhesion molecule-1 (ICAM-1), and CD31; then assessed by enumeration of stained blood vessels (percentage positive blood vessels) blinded to knowledge of clinical information. Results. There was a significant increase in the prevalence of blood vessels that stained for mEPCR and ICAM-1 in patients compared to controls [94% vs 59% (p = 0.045) and 81% vs 67% (p = 0.037), respectively]. Adiponectin staining and CD31 staining were similar between the groups (45% vs 43% and 98% vs 92%). Dermal staining for mEPCR was greater in patients with proliferative glomerulonephritis than in those with membranous disease (96% vs 60%; p = 0.029). A composite of poor prognostic renal markers and death was significantly associated with greater expression of mEPCR staining. Conclusion. These data are consistent with the notion that in patients with LN, activation of the microvasculature extends beyond the clinically targeted organ. The insidious expression of this widespread vasculopathy may be a contributor to longterm comorbidities. The Journal of Rheumatology

Original languageEnglish
Pages (from-to)510-515
Number of pages6
JournalJournal of Rheumatology
Volume39
Issue number3
DOIs
StatePublished - Mar 1 2012
Externally publishedYes

Fingerprint

Lupus Nephritis
Microvessels
Protein C
Membrane Proteins
Skin
Staining and Labeling
Blood Vessels
Intercellular Adhesion Molecule-1
Adiponectin Receptors
Kidney
Buttocks
Adiponectin
Rheumatology
Glomerulonephritis
Comorbidity
Biopsy
Antibodies

Keywords

  • Glomerular filtration rate
  • Lupus nephritis
  • Proteinuria
  • Skin biopsy
  • Systemic lupus erythematosus
  • Vasculopathy

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

Cite this

Izmirly, P. M., Shvartsbeyn, M., Meehan, S., Franks, A., Braun, A., Ginzler, E., ... Clancy, R. M. (2012). Dysregulation of the microvasculature in nonlesional non-sun-exposed skin of patients with lupus nephritis. Journal of Rheumatology, 39(3), 510-515. https://doi.org/10.3899/jrheum.110878

Dysregulation of the microvasculature in nonlesional non-sun-exposed skin of patients with lupus nephritis. / Izmirly, Peter M.; Shvartsbeyn, Marianna; Meehan, Shane; Franks, Andrew; Braun, Alan; Ginzler, Ellen; Xu, Sherry X.; Yee, Herman; Rivera, Tania; Esmon, Charles; Barisoni-Thomas, Laura; Merrill, Joan T.; Buyon, Jill P.; Clancy, Robert M.

In: Journal of Rheumatology, Vol. 39, No. 3, 01.03.2012, p. 510-515.

Research output: Contribution to journalArticle

Izmirly, PM, Shvartsbeyn, M, Meehan, S, Franks, A, Braun, A, Ginzler, E, Xu, SX, Yee, H, Rivera, T, Esmon, C, Barisoni-Thomas, L, Merrill, JT, Buyon, JP & Clancy, RM 2012, 'Dysregulation of the microvasculature in nonlesional non-sun-exposed skin of patients with lupus nephritis', Journal of Rheumatology, vol. 39, no. 3, pp. 510-515. https://doi.org/10.3899/jrheum.110878
Izmirly, Peter M. ; Shvartsbeyn, Marianna ; Meehan, Shane ; Franks, Andrew ; Braun, Alan ; Ginzler, Ellen ; Xu, Sherry X. ; Yee, Herman ; Rivera, Tania ; Esmon, Charles ; Barisoni-Thomas, Laura ; Merrill, Joan T. ; Buyon, Jill P. ; Clancy, Robert M. / Dysregulation of the microvasculature in nonlesional non-sun-exposed skin of patients with lupus nephritis. In: Journal of Rheumatology. 2012 ; Vol. 39, No. 3. pp. 510-515.
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abstract = "Objective. Membrane endothelial protein C receptor (mEPCR) is highly expressed in peritubular capillaries of kidneys from patients with active and poorly responsive lupus nephritis (LN). We investigated the hypothesis that changes in the microvasculature are widespread with extension to the dermal vasculature. Methods. Skin biopsies from uninvolved skin (buttocks) were performed in 27 patients with LN and 5 healthy controls. Sections were stained with specific antibodies reactive with mEPCR, adiponectin, intercellular adhesion molecule-1 (ICAM-1), and CD31; then assessed by enumeration of stained blood vessels (percentage positive blood vessels) blinded to knowledge of clinical information. Results. There was a significant increase in the prevalence of blood vessels that stained for mEPCR and ICAM-1 in patients compared to controls [94{\%} vs 59{\%} (p = 0.045) and 81{\%} vs 67{\%} (p = 0.037), respectively]. Adiponectin staining and CD31 staining were similar between the groups (45{\%} vs 43{\%} and 98{\%} vs 92{\%}). Dermal staining for mEPCR was greater in patients with proliferative glomerulonephritis than in those with membranous disease (96{\%} vs 60{\%}; p = 0.029). A composite of poor prognostic renal markers and death was significantly associated with greater expression of mEPCR staining. Conclusion. These data are consistent with the notion that in patients with LN, activation of the microvasculature extends beyond the clinically targeted organ. The insidious expression of this widespread vasculopathy may be a contributor to longterm comorbidities. The Journal of Rheumatology",
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AU - Izmirly, Peter M.

AU - Shvartsbeyn, Marianna

AU - Meehan, Shane

AU - Franks, Andrew

AU - Braun, Alan

AU - Ginzler, Ellen

AU - Xu, Sherry X.

AU - Yee, Herman

AU - Rivera, Tania

AU - Esmon, Charles

AU - Barisoni-Thomas, Laura

AU - Merrill, Joan T.

AU - Buyon, Jill P.

AU - Clancy, Robert M.

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N2 - Objective. Membrane endothelial protein C receptor (mEPCR) is highly expressed in peritubular capillaries of kidneys from patients with active and poorly responsive lupus nephritis (LN). We investigated the hypothesis that changes in the microvasculature are widespread with extension to the dermal vasculature. Methods. Skin biopsies from uninvolved skin (buttocks) were performed in 27 patients with LN and 5 healthy controls. Sections were stained with specific antibodies reactive with mEPCR, adiponectin, intercellular adhesion molecule-1 (ICAM-1), and CD31; then assessed by enumeration of stained blood vessels (percentage positive blood vessels) blinded to knowledge of clinical information. Results. There was a significant increase in the prevalence of blood vessels that stained for mEPCR and ICAM-1 in patients compared to controls [94% vs 59% (p = 0.045) and 81% vs 67% (p = 0.037), respectively]. Adiponectin staining and CD31 staining were similar between the groups (45% vs 43% and 98% vs 92%). Dermal staining for mEPCR was greater in patients with proliferative glomerulonephritis than in those with membranous disease (96% vs 60%; p = 0.029). A composite of poor prognostic renal markers and death was significantly associated with greater expression of mEPCR staining. Conclusion. These data are consistent with the notion that in patients with LN, activation of the microvasculature extends beyond the clinically targeted organ. The insidious expression of this widespread vasculopathy may be a contributor to longterm comorbidities. The Journal of Rheumatology

AB - Objective. Membrane endothelial protein C receptor (mEPCR) is highly expressed in peritubular capillaries of kidneys from patients with active and poorly responsive lupus nephritis (LN). We investigated the hypothesis that changes in the microvasculature are widespread with extension to the dermal vasculature. Methods. Skin biopsies from uninvolved skin (buttocks) were performed in 27 patients with LN and 5 healthy controls. Sections were stained with specific antibodies reactive with mEPCR, adiponectin, intercellular adhesion molecule-1 (ICAM-1), and CD31; then assessed by enumeration of stained blood vessels (percentage positive blood vessels) blinded to knowledge of clinical information. Results. There was a significant increase in the prevalence of blood vessels that stained for mEPCR and ICAM-1 in patients compared to controls [94% vs 59% (p = 0.045) and 81% vs 67% (p = 0.037), respectively]. Adiponectin staining and CD31 staining were similar between the groups (45% vs 43% and 98% vs 92%). Dermal staining for mEPCR was greater in patients with proliferative glomerulonephritis than in those with membranous disease (96% vs 60%; p = 0.029). A composite of poor prognostic renal markers and death was significantly associated with greater expression of mEPCR staining. Conclusion. These data are consistent with the notion that in patients with LN, activation of the microvasculature extends beyond the clinically targeted organ. The insidious expression of this widespread vasculopathy may be a contributor to longterm comorbidities. The Journal of Rheumatology

KW - Glomerular filtration rate

KW - Lupus nephritis

KW - Proteinuria

KW - Skin biopsy

KW - Systemic lupus erythematosus

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