title: Clinical relevance of elevated serum thrombomodulin and soluble E-selectin in patients with Wegener's granulomatosis and other systemic vasculitides.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Internal Medicine IV, University of Heidelberg, Germany.
authors.forename: M W
authors.initials: MW
authors.lastname: Boehme
authors.forename: W H
authors.initials: WH
authors.lastname: Schmitt
authors.forename: P
authors.initials: P
authors.lastname: Youinou
authors.forename: W R
authors.initials: WR
authors.lastname: Stremmel
authors.forename: W L
authors.initials: WL
authors.lastname: Gross
mesh_terms: D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D001528:Behcet Syndrome / Q000097:blood / Q000276:immunology; D002097:C-Reactive Protein / Q000032:analysis; D019040:E-Selectin / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D013700:Giant Cell Arteritis / Q000097:blood / Q000276:immunology; D014890:Granulomatosis with Polyangiitis / Q000097:blood* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010488:Polyarteritis Nodosa / Q000097:blood / Q000276:immunology; D012189:Retrospective Studies; D013625:Takayasu Arteritis / Q000097:blood / Q000276:immunology; D018180:Thrombomodulin / Q000097:blood*; D014657:Vasculitis / Q000097:blood* / Q000276:immunology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D019040:E-Selectin; D018180:Thrombomodulin; D002097:C-Reactive Protein