Chemokine (CXC motif) ligand 9 serum levels in mixed cryoglobulinemia are associated with circulating levels of IFN-γ and TNF-α

OBJECTIVES: 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