title: Chemokine (CXC motif) ligand 9 serum levels in mixed cryoglobulinaemia are associated with circulating levels of IFN-gamma and TNF-alpha.
abstract: OBJECTIVE
  No study evaluated circulating chemokine (CXC motif) ligand (CXCL)9 in 'patients with mixed cryoglobulinaemia and hepatitis C virus chronic infection' (MC+HCV). We aimed to measure CXCL9, IFN-γ and TNF-α in a series of MC+HCV to correlate these parameters to different clinical phenotypes.
  
  
  METHODS
  Serum CXCL9, IFN-γ and TNF-α were assayed in 54 MC+HCV, in 54 patients with HCV chronic infection (HCV+) and in 54 sex- and age-matched controls.
  
  
  RESULTS
  MC+HCV showed significantly higher mean CXCL9 than HCV+ patients (p=0.01; ANOVA) or controls (p=0.0001; ANOVA), in particular in 21 cryoglobulinaemic patients with active vasculitis compared to those without (p<0.001; ANOVA). Serum IFN-γ (in patients with detectable IFN-γ) and TNF-α were significantly higher in MC+HCV than in controls (p<0.05, Mann-Whitney U test; p<0.0001, Mann-Whitney U-test; respectively). CXCL9, evaluated by classes of IFN-γ (IFN-γ<2; 2<IFN-γ<5; IFN-γ>5 pg/mL), or TNF-α (TNF-α<2; 2<TNF-α<10; TNF-α>10 pg/mL), showed a progressive, but not significant, increase of circulating values. When the combination of high circulating levels of IFN-γ and TNF-α (IFN-γ>2 and TNF-α>10 pg/mL vs. IFN-γ<2 and/or TNF-α<10 pg/mL) was evaluated, significantly higher CXCL9 levels were observed (p<0.01; ANOVA).
  
  
  CONCLUSIONS
  We demonstrated markedly high serum levels of CXCL9 in MC+HCV (vs. HCV+ patients or healthy controls), significantly associated with the presence of active vasculitis. A strong relation among high levels of circulating IFN-γ, TNF-α and serum CXCL9 has been shown in MC+HCV. Larger patients' series will be needed to evaluate the relevance of serum CXCL9 determination as clinico-prognostic marker of MC+HCV.
authors: Department of Internal Medicine University of Pisa School of Medicine, Pisa, Italy. alessandro.antonelli@med.unipi.it
authors: Alessandro
authors: A
authors: Antonelli
authors: Poupak
authors: P
authors: Fallahi
authors: Silvia Martina
authors: SM
authors: Ferrari
authors: Alda
authors: A
authors: Corrado
authors: Marco
authors: M
authors: Sebastiani
authors: Andreina
authors: A
authors: Manfredi
authors: Silvia
authors: S
authors: Frascerra
authors: Mario
authors: M
authors: Miccoli
authors: Anna Linda
authors: AL
authors: Zignego
authors: Ele
authors: E
authors: Ferrannini
authors: Clodoveo
authors: C
authors: Ferri
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D054370:Chemokine CXCL9 / Q000097:blood*; D016009:Chi-Square Distribution; D003449:Cryoglobulinemia / Q000097:blood / Q000276:immunology*; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D015854:Up-Regulation; D014657:Vasculitis / Q000097:blood / Q000276:immunology
chemical_list: D015415:Biomarkers; C080810:CXCL9 protein, human; D054370:Chemokine CXCL9; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma