CLINICAL RELEVANCE OF ELEVATED SERUM THROMBOMODULIN AND SOLUBLE E-SELECTIN IN PATIENTS WITH WEGENERS 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 follo wing cell damage and was therefore investigated as a parameter of dise ase activity in patients with Wegener's granulomatosis (WG) and variou s other vasculitides. PATIENTS AND METHODS: One hundred and ninety-sev en sera of 102 patients with histologically proven WG of different dis ease activity and 41 sera of patients with other vasculitides at their active stage were investigated (12 Takayasu arteritis [TA], 7 giant c ell arteritis [GCA], 10 polyarteritis nodosa [PAN], 12 Behcet's diseas e [BD]). The sera were examined for the levels of sTM and sE-selectin (CD62E) by enzyme-linked immunosorbent assay (ELISA) and for the prese nce of classical anti-neutrophil cytoplasmic antibodies (cANCA) by ind irect immunofluorescence (IIF). The disease activity was evaluated acc ording to the clinical symptoms and organ involvement. RESULTS: A sign ificant 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, p artial remission: 60 +/- 5 ng/ml; generalized WG, partial remission: 7 5 +/- 7 ng/ml; active TA: 36 +/-; active GCA: 36 +/- 4 ng/ml, active P AN: 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 val ues closely reflected relapses and therapy-induced remissions of WG. E levated cANCA titers were correlated as well with the disease activity in WG but more weakly than sTM levels. In contrast, sE-selectin value s 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 da mage. sTM might prove to be a clinically useful marker for therapeutic considerations.