Levels of soluble VCAM-1, soluble ICAM-1, and soluble E-selectin during disease exacerbations in patients with systemic lupus erythematosus (SLE); a long term prospective study

Abstract

SUMMARYActive SLE is characterized by immune deposits and subsequent vascular inflammation in many organs. Expression and up-rcgulation of adhesion molecules is basic to migration of inflammatory cells into the tissues. Recently, soluble isoforms of these molecules have been described which might be an expression of their up-regulation in the tissues and, as such, of disease activity. The purpose of this study was to evaluate whether changes in levels of soluble adhesion molecules reflect disease activity. We analysed .serial sera in a 6-month period preceding 22 consecutive exacerbations of SLE for levels of soluble vascular cell adhesion molecule-l (sVCAM-1). soluble intercellular adhesion molecule-l (slCAM-1), and sE-selectin. Levels were related to clinical disease activity (SLEDAI). and levels of anti-dsDNA and complement. At the time of maximal disease activity, levels of sVCAM-1 in patients with SLE were higher than those in controls (A" < 00001), levels in patients with renal involvement being higher than in those without {P < 0 02). Levels of sVCAM-1 correlated with SLEDAI scores {P < 0 05) and, inversely, with levels of C3 (P = 0 01). In addition, in the presence of anti-dsDNA, levels of sVCAM-1 tended to correlate with levels of these autoantibodies (P < 01). Levels of sICAM-1 were normal and sEselectin levels even decreased compared with controls. Levels of sVCAM-l were higher at the moment of relapse {P = 0 001) than at 6 months before this time point. This rise correlated with the rise in SLEDAI score (f < 0 02). l.evelsof sICAM-l and sE-selectin did not rise, and remained in the normal range in all exacerbations studied. In conclusion, in contrast to sICAM-1 and sEselectin, levels of sVCAM-l are increased, rise parallel to disease activity during exacerbations in SLE, and are associated with decreasing levels of complement factors. This favours the hypothesis of immune deposit formation, activation of the complement cascade and activation of endothelial cells. Concurrent up-regulation of vascular adhesion molecules may thus result in transmigration of activated inflammatory cells inducing tissue damage.

Excreted urinary mediators in an animal model of experimental immune nephritis with potential pathogenic significance

“…In addition, it is clear that infiltrating leukocytes may be another good source of this molecule. The present findings indicate the VCAM-1 may be a potential urinary marker of renal disease in mice with experimental immune-mediated nephritis, concordant with earlier studies of lupus nephritis (33). In addition, it appears that elevated urinary VCAM-1 levels may persist even after active renal inflammation subsides ( Figure 2).…”

Biochemistry of Nitric Oxide

“…Patients with SLE showed upregulation of iNOS in normal appearing vascular endothelium. These endothelium also over express the soluble vascular adhesion molecules Intracellular cell adhesion molecule (ICAM-1), E-Selectin and Vascular cell adhesion molecule (VCAM) [36] as have been reported in active SLE [37]. Therefore, it appears that endothelium plays an active role in the localization and propagation of leukocyte and antibody-mediated inflammation [38].…”

Increased urinary levels of the leukocyte adhesion molecules ICAM-1 and VCAM-1 in human lupus nephritis with advanced renal histological changes: preliminary findings

“…Spearman's test was applied for detecting correlations between urinary adhesion molecules and serum complement levels. If normal distribution could not be assumed, the Mann-Whitney U test or Wilcoxon's paired rank-sum test was applied; p \ 0.05 (two-sided) was considered significant [33].…”