title: Monocyte activation and relationship to anti-proteinase 3 in acute vasculitis.
abstract: BACKGROUND
  Monocytes have been suggested to play a role in antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis, but their state of activation in vivo in patients is still unknown.
  
  
  METHODS
  Twelve consecutive patients with acute anti-proteinase 3 (PR3)-positive vasculitis were included prospectively, and blood samples were drawn at diagnosis. As controls, peripheral blood was obtained from a group of patients with acute infection (n = 12) and from healthy controls (n = 12). Monocyte activation was estimated from the expression of adhesion molecules (CD62L and CD11b), production of oxygen radicals and serum concentrations of soluble inflammation markers and adhesion molecules [intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1)].
  
  
  RESULTS
  Compared with monocytes from healthy subjects, monocytes from patients with acute vasculitis expressed upregulated CD11b (P < 0.05) but had reduced production of oxygen radicals (P < 0.01). A high concentration of anti-PR3 correlated with decreased expression of CD62L (r = 0.71, P = 0.009) and increased expression of CD11b (r = 0.63, P = 0.02). The serum concentrations of soluble inflammation markers [soluble CD14, interleukin (IL)-6, tumour necrosis factor receptor 1 (TNFR1), IL-10 and IL-8] as well as soluble adhesion molecules (sVCAM-1 and sICAM-1) were increased. Monocytes in patients with acute vasculitis displayed a reduced production of oxygen free radicals (P < 0.01) but similar serum concentrations of soluble inflammation markers and adhesion molecules, as compared with the control group of patients with acute infection and negative PR3-ANCA.
  
  
  CONCLUSIONS
  High anti-PR3 concentration in patients with acute vasculitis correlated with an activated adhesion molecule phenotype (CD62L(low)/CD11b(high)) in circulating monocytes, indicating a potential pathophysiological role for anti-PR3. An impaired production of oxygen radicals in monocytes in patients with vasculitis compared with those with acute infection may mirror the longer time interval from onset of first symptoms to admission, in patients with vasculitis.
authors.affiliation: Department of Medicine, Division of Clinical Immunology and Transfusion Medicine and Division of Nephrology, Karolinska Hospital and Karolinska Institutet, Stockholm, Sweden. Wikman@hs.se
authors.forename: Agneta
authors.initials: A
authors.lastname: Wikman
authors.forename: Anna
authors.initials: A
authors.lastname: Fagergren
authors.forename: S
authors.initials: S
authors.lastname: Gunnar O  Johansson
authors.forename: Joachim
authors.initials: J
authors.lastname: Lundahl
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Jacobson
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000276:immunology; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin; D011446:Prospective Studies; D017382:Reactive Oxygen Species / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology*; D014657:Vasculitis / Q000276:immunology*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D015815:Cell Adhesion Molecules; D016207:Cytokines; D017382:Reactive Oxygen Species; D012697:Serine Endopeptidases; D053146:Myeloblastin