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DOI: 10.1055/s-0033-1361030
Higher frequency of peripheral CD3CXCR3 and CD4CXCR3 positive blood cells in HCV patients in context of bile acid retention
Background: Chronic hepatitis C infection is worldwide a leading cause of end stage liver disease. High levels of serum interferon-gamma-inducible protein-10 (IP-10) are associated to inferior antiviral therapy response. In a cohort of 300 HCV patients we recently showed an association between higher IP-10 serum levels, cholestasis and higher DPPIV serum activity. DPPIV was described as cleavage enzyme of serum IP-10 (Casrouge et al., JCI 2011) which induces an antagonist form of IP-10.
Aims: To analyse PBMCs together with serum BA differentiation, DPPIV activity and IP-10 serum levels in patients with chronic hepatitis C infection and healthy controls.
Methods: A prospective cohort of 27 patients with chronic HCV genotype 1 infection and 17 healthy controls were included in this study. FACS analysis of CD3CXCR3, CD4CXCR3 and CD8CXCR3 positive peripheral blood cells together with serum BA differentiation by GC/MS analysis and analysis of serum DPPIV activity as well as IP-10 levels were performed.
Results: HCV patients had significantly higher BA serum levels compared to healthy controls and showed a higher frequency of CXCR3 positive cells in peripheral blood. Higher IP-10 serum levels were associated to higher frequency of CD3CXCR3 and CD4CXCR3 positive blood cells. Furthermore serum BA differentiation showed an association between higher IP-10 serum levels and higher levels of different taurine- and glycine conjugated BAs.
Conclusions: Higher frequency of circulating CD3CXCR3 and CD4CXCR3 positive blood cells in HCV patients might be caused by increased DPPIV activity in the context of bile acid accumulation and subsequent increase in cleaved antagonist forms of IP-10. It appears speculative whether increased peripheral CXCR3-positive T-cells reflect an inferior recruitment and antiviral response in the liver.