Circulating soluble adhesion molecules in ANCA-associated vasculitis

Background. To evaluate whether changes in concentrations of soluble (s) E- selectin, sP-selectin, sL-selectin, intercellular adhesion molecule I (sICA M-1), and vascular cell adhesion molecule 1 (sVCAM-1) reflect disease activ ity in patients with ANCA-associated vasculitis and whether serum levels of these adhesion molecules are related to the degree of renal failure in pat ients with chronic renal failure (CRF). Subjects and methods. A sandwich ELISA was used to measure these soluble ad hesion molecules in (ii) sera from 20 patients with antineutrophil cytoplas mic antibody (ANCA)-associated vasculitis (10 patients with Wegener's granu lomatosis (WG) and 10 patients with microscopic polyangiitis (MPA)), obtain ed at the time of diagnosis and during the remission period; (ii) sera from 40 patients with CRF not undergoing haemodialysis. Results. At the time of diagnosis, serum levels of sE-selectin, sICAM-1 and sVCAM-1 (88 +/- 42 ng/ml, 437 +/- 184 ng/ml, 1720 +/- 1174 ng/ml respectiv ely) were significantly higher in patients with ANCA-associated vasculitis than in healthy controls (P < 0.0001, P = 0.002 and P = 0.001 respectively) . Serum sP-selectin values did not differ from those obtained in normal don ors. In contrast, sl-selectin levels (940 <plus/minus> 349 ng;ml) were sign ificantly lower in patients than those recorded in healthy controls (P < 0. 0001). A significant decrease in concentrations of sE-selectin, sP-selectin , sICAM-1, and sVCAM-1 was observed between active and remission phases (P < 0.0001, P = 0.002, P=0.001 and P = 0.001 respectively). No significant di fferences were observed in sL-selectin levels between active and remission phases. sl-selectin concentrations (802 +/- 306 ng/ml) during the remission phase remained lower than those observed in healthy controls (P < 0.0001). No correlation was observed between serum creatinine and sE-selectin, sP-s electin, sICAM-1 and sVCAM-1 in patients of the CRF group. A slight negativ e correlation was established between creatinine and sl-selectin concentrat ion. Conclusions. Increased serum levels of sE-selectin, sICAM-1, and sVCAM-1 an d decreased levels of sl-selectin in active ANCA-associated vasculitis, and the normalization of sE-selectin, sICAM-1, and sVCAM-1 during the remissio n phase suggest that the concentration of soluble levels of these adhesion molecules reflects disease activity. The decrease in sP-selectin levels bet ween active and inactive phases also suggest that this receptor may reflect clinical activity. The lack of correlation between serum levels of sE-sele ctin, sP-selectin. sICAM-1, and sVCAM-1 and the degree of renal failure in patients with CRF Suggests that the mechanism of clearance of these molecul es is not renal.