RT Journal Article
SR Electronic
T1 Dysregulation of the Microvasculature in Nonlesional Non-Sun-exposed Skin of Patients with Lupus Nephritis
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.110878
DO 10.3899/jrheum.110878
A1 Peter M. Izmirly
A1 Marianna Shvartsbeyn
A1 Shane Meehan
A1 Andrew Franks
A1 Alan Braun
A1 Ellen Ginzler
A1 Sherry X. Xu
A1 Herman Yee
A1 Tania Rivera
A1 Charles Esmon
A1 Laura Barisoni
A1 Joan T. Merrill
A1 Jill P. Buyon
A1 Robert M. Clancy
YR 2012
UL http://www.jrheum.org/content/early/2012/01/26/jrheum.110878.abstract
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.