Low levels of vitronectin and clusterin in acute meningococcal disease are closely associated with formation of the terminal-complement complex and the vitronectin-thrombin-antithrombin complex.
Patients with terminal complement deficiencies and thus impaired lytic efficiency have a highly increased likelihood of contracting invasive meningococcal infections but generally experience a mild disease course. Deficiencies of lysis inhibitors might therefore be associated with severe disease. We have quantified the complement lysis inhibitors vitronectin and clusterin, as well as complexes containing the proteins, in plasma from patients with acute meningococcal disease. At hospital admission, the median vitronectin concentrations were 0.10 (range, 0.04 to 0.17) g/liter in 10 septic patients and 0.19 (0.09 to 0.47) g/liter in 14 nonseptic patients (P = 0.001). The corresponding clusterin concentrations were 0.09 (0.01 to 0.13) and 0.14 (0.06 to 0.29) g/liter (P = 0.005). The vitronectin-thrombin-antithrombin complex concentration was 1.8 (0.22 to 35.6) arbitrary units (AU)/ml in septic patients, but the complex was not detectable in most nonseptic patients (< 0.10 to 0.16 AU/ml) (P < 0.0001). The corresponding levels of the terminal complement complex (contains vitronectin and clusterin) were 4.4 (3.6 to 20.1) and 2.6 (1.6 to 4.7) AU/ml (P = 0.0005). We found no evidence of constitutively low levels of vitronectin or clusterin in patients contracting meningococcal disease. The low levels of the proteins may partly be explained by hemodilution, extravasation, and increased consumption due to incorporation into complexes which are quickly removed from circulation.
Høgåsen
K
K
Department of Immunology and Transfusion Medicine, Nordland Central Hospital, Bodø, Norway.
Mollnes
T E
TE
Brandtzaeg
P
P
D000293:Adolescent; D000328:Adult; D000991:Antithrombins / Q000378:metabolism*; D051152:Clusterin; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D008297:Male; D008585:Meningitis, Meningococcal / Q000276:immunology*; D008875:Middle Aged; D018832:Molecular Chaperones; D009345:Neisseria meningitidis; D011485:Protein Binding; D018805:Sepsis / Q000276:immunology; D013917:Thrombin / Q000378:metabolism*; D019096:Vitronectin
D000991:Antithrombins; C495242:CLU protein, human; D051152:Clusterin; D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; D046911:Macromolecular Substances; D018832:Molecular Chaperones; D019096:Vitronectin; D013917:Thrombin