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


CONCLUSIONS
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.
Department of Medicine, NYU School of Medicine, New York, NY 10016, USA.
Peter M
PM
Izmirly
Marianna
M
Shvartsbeyn
Shane
S
Meehan
Andrew
A
Franks
Alan
A
Braun
Ellen
E
Ginzler
Sherry X
SX
Xu
Herman
H
Yee
Tania L
TL
Rivera
Tania
T
Rivera
Charles
C
Esmon
Laura
L
Barisoni
Joan T
JT
Merrill
Jill P
JP
Buyon
Robert M
RM
Clancy
D052242:Adiponectin / Q000378:metabolism; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002196:Capillaries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016022:Case-Control Studies; D000074283:Endothelial Protein C Receptor; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008181:Lupus Nephritis / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism; D012867:Skin / Q000098:blood supply* / Q000473:pathology
D052242:Adiponectin; D015703:Antigens, CD; D015415:Biomarkers; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; D018799:Intercellular Adhesion Molecule-1