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

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.,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.,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.,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.