Clinical implications of serum thrombomodulin in PR3-ANCA-associated vasculitis

BACKGROUND: Vascular injury is the main mechanism in pathophysiology of PR3-ANCA-associated vasculitis. Soluble serum thrombomodulin (sTM) is a membrane-bound receptor for thrombin expressed by vascular endothelial cells. OBJECTIVE: The aim of study was to determine the blood levels of sTM in patients with PR3-ANCA-associated vasculitis. MATERIAL AND METHODS: Twenty five patients with Wegener's granulomatosis (WG), 13 with generalized WG and 12 with limited WG, with histologically proven disease, and 15 healthy subjects as a control were investigated. An ELISA for detection of sTM and PR3-ANCA was performed. The disease activity was evaluated according to BVAS and DEI indexes. RESULTS: Significant increases in sTM were found in both active generalized and limited active WG compared with control values: 108 ± 12, 56 ± 2, and 12 ± 4 ng/ml, respectively. Elevated ANCA titer correlated with disease activity, but more weakly than sTM levels did. Elevated sTM concentration is a result of vascular endothelial injury in the course of PR3-ANCA associated vasculitis. CONCLUSIONS: Soluble serum thrombomodulin is a promising, both diagnostic and therapeutic, marker of endothelial cell injury in relation to disease activity and progression in autoimmune disorders, reflecting the degree of endothelial cell damage.