Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Dysregulation of the Microvascular as Assessed by Expression of Protective and Injury Associated Markers Is Reflected in the Non-Lesional Non-Sunexposed Skin of Patients with Lupus Nephritis.
Izmirly1, Peter M., Meehan2, Shane, Xu2, Sherry X., Askanase1, Anca D., Merrill3, Joan T., Buyon1, Jill P., Clancy4, Robert M.
Coagulation is one of the first pathways to be elicited by vascular injury, and its activation is followed by proinflammatory phenomena, in part due to loss of the anti-inflammatory activity of both the Protein C pathway and membrane Endothelial Protein C receptor (mEPCR). It has been recently demonstrated that mEPCR is highly expressed in the cortical peritubular capillaries of kidneys from patients (pts) with active lupus nephritis compared to normal human kidney. Profound upregulation of mEPCR was observed even in areas absent tubulointerstitial damage. This study addressed the hypothesis that changes in the microvasculature extend beyond the clinically targeted organ and that dysregulation is a fundamental characteristic of SLE.
The study included SLE pts in whom renal disease was considered active as assessed by proteinuria and urinary sediment. Renal biopsies were performed in all pts. Thirty skin biopsies from non-lesional non-sunexposed skin (buttocks) were obtained in 26 pts (23 females, 3 males) and five healthy controls (4 females, 1 male). The paraffin skin sections were individually stained with specific antibodies against mEPCR and adiponectin (protective markers), ICAM-1 (proinflammatory) and CD31 (pan endothelial marker). Immunohistochemistry (IHC) was scored by counting peroxidase-brown labeled blood vessels (1020 microns in diameter) without knowledge of the clinical information associated with the biopsy. The number of blood vessels with an intensity of at least 1+ were quantitatively scored with ranges 112. To account for the number of blood vessels per slide, the CD31 count had to be 12 to be included in the analysis.
The 28 renal biopsies comprised the following ISN/RPS classifications: 4 Class III, 7 Class IV, 8 Class V, I Class VI, 3 Class III/V, 3 Class IV/V. Nineteen percent of the pts had a GFR <60 (mean GFR, 82 ml/min). Abnormal laboratory values for complement and anti-dsDNA antibodies were reported in 72% and 75% of pts, respectively. Nephrotic range proteinuria was present in 37%. For IHC skin assessments of the controls, the mean score for mEPCR was 1 (highest 2), ICAM-1 was 4 (highest 7) and adiponectin was 1 (highest 2). In 17/25 (68%) of the SLE non-lesional non-sun exposed skin sections, mEPCR was expressed above the highest control. In 16/30 (53%) ICAM-1 staining exceeded 7. In contrast, only 6/25 (19%) expressed adiponectin above 2. For each specific stain there were no apparent differences between biopsy class, degree of proteinuria, presence of anti dsDNA or low complement levels. However, pts with mEPCR staining above 2 had higher GFR measurements than those with staining < 2 (88 ml/min ± 31 versus 53 ± 32, p= 0.0168). In contrast, GFR was unrelated to ICAM-1 and adiponectin expression.
These data are consistent with the notion that there is widespread activation of the microvasculature. The capacity of endothelial cells to utilize anticoagulation pathways is not restricted to the kidney and expression of mEPCR in the microcirculation likely represents an attempt to limit microvascular inflammation in kidney and skin.
To cite this abstract, please use the following information:
Izmirly, Peter M., Meehan, Shane, Xu, Sherry X., Askanase, Anca D., Merrill, Joan T., Buyon, Jill P., et al; Dysregulation of the Microvascular as Assessed by Expression of Protective and Injury Associated Markers Is Reflected in the Non-Lesional Non-Sunexposed Skin of Patients with Lupus Nephritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1190