Clinical relevance of elevated serum thrombomodulin and soluble E- selectin in patients with Wegener's granulomatosis and other systemic vasculitides

PURPOSE: Vascular injury plays an important pathophysiological role in vasculitis. Soluble serum thrombomodulin (sTM), a promising marker of endothelial cell injury, is released into the circulating blood following cell damage and was therefore investigated as a parameter of disease activity in patients with Wegener's granulomatosis (WG) and various other vasculitides. PATIENTS AND METHODS: One hundred and ninety-seven sera of 102 patients with histologically proven WG of different disease activity and 41 sera of patients with other vasculitides at their active stage were investigated (12 Takayasu arteritis [TA], 7 giant cell arteritis [GCA], 10 polyarteritis nodosa [PAN], 12 Behcet's disease [BD]). The sera were examined for the levels of sTM and sE-selectin (CD62E) by enzyme-linked immunosorbent assay (ELISA) and for the presence of classical anti-neutrophil cytoplasmic antibodies (cANCA) by indirect immunofluorescence (IIF). The disease activity was evaluated according to the clinical symptoms and organ involvement. RESULTS: A significant increase of sTM levels compared with control values (26 ± 2 ng/ml) was found in active WG, TA, GCA, PAN, and BD: limited active WG: 63 ± ng/ml; generalized active WG: 119 ± 15 ng/ml; limited WG, partial remission: 60 ± 5 ng/ml; generalized WG, partial remission: 75 ± 7 ng/ml; active TA: 36 ±; active GCA: 36 ± 4 ng/ml, active PAN: 33 ± 2 ng/ml, active BD: 40 ± 4 ng/ml. Limited and generalized WG in complete remission did not have elevated levels of sTM. sTM values closely reflected relapses and therapy-induced remissions of WG. Elevated cANCA titers were correlated as well with the disease activity in WG but more weakly than sTM levels. In contrast, sE-selectin values were not significantly correlated with the disease activity and the course of disease. CONCLUSIONS: sTM is a promising serological marker of disease activity and progression in active limited and generalized WG and other vasculitides reflecting the degree of endothelial cell damage. sTM might prove to be a clinically useful marker for therapeutic considerations.