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

Active SLE is characterized by immune deposits and subsequent vascular inflammation in many organs. Expression and up-regulation of adhesion molecules is basic to migration of inflammatory cells into the tissue s. Recently, soluble isoforms of these molecules have been described w hich might be an expression of their up-regulation in the tissues and, as such, of disease activity. The purpose of this study was to evalua te whether changes in levels of soluble adhesion molecules reflect dis ease activity. We analysed serial sera in a 6-month period preceding 2 2 consecutive exacerbations of SLE for levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecul e-1 (sICAM-1), and sE-selectin. Levels were related to clinical diseas e activity (SLEDAI), and levels of anti-dsDNA and complement. At the t ime of maximal disease activity, levels of sVCAM-1 in patients with SL E were higher than those in controls (P < 0.0001), 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, invers ely, with levels of C3 (P = 0.01). In addition, in the presence of ant i-dsDNA, levels of sVCAM-1 tended to correlate with levels of these au toantibodies (P < 0.1). Levels of sICAM-1 were normal and sE-selectin levels even decreased compared with controls. Levels of sVCAM-1 were h igher at the moment of relapse (P = 0.001) than at 6 months before thi s time point. This rise correlated with the rise in SLEDAI score (P < 0.02). Levels of sICAM-1 and sE-selectin did not rise, and remained in the normal range in all exacerbations studied. In conclusion, in cont rast to sICAM-1 and sE-selectin, levels of sVCAM-1 are increased, rise parallel to disease activity during exacerbations in SLE, and are ass ociated 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 ac tivated inflammatory cells inducing tissue damage.