PLoS ONE (Jan 2018)

Serum IP-10 levels and increased DPPIV activity are linked to circulating CXCR3+ T cells in cholestatic HCV patients.

  • Monika Rau,
  • Johannes Schmitt,
  • Thomas Berg,
  • Andreas E Kremer,
  • Bruno Stieger,
  • Katharina Spanaus,
  • Bertram Bengsch,
  • Marta R Romero,
  • Jose J Marin,
  • Verena Keitel,
  • Hartwig Klinker,
  • Hans-Peter Tony,
  • Beat Müllhaupt,
  • Andreas Geier

DOI
https://doi.org/10.1371/journal.pone.0208225
Journal volume & issue
Vol. 13, no. 12
p. e0208225

Abstract

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Background & aimsSerum interferon-gamma-inducible protein-10 (IP-10) is elevated in cholestatic liver diseases and predicts response to antiviral therapy in patients with chronic hepatitis C virus (HCV) infection. Dipeptidylpeptidase 4 (DPPIV) cleaves active IP-10 into an inactive form, which inhibits recruitment of CXCR3+ T cells to the liver. In this study the link between IP-10 levels, DPPIV activity in serum and CXCR3+ T cells is analysed in cholestatic and non-cholestatic liver patients.MethodsIn serum DPPIV activity (by enzymatic assay), IP-10 (by ELISA) and bile acids (BA) (by enzymatic assay) were analysed in 229 naive HCV genotype (GT) 1 patients and in 16 patients with cholestatic liver disease. In a prospective follow-up (FU) cohort of 27 HCV GT 1 patients peripheral CD3+CXCR3+, CD4+CXCR3+ and CD8+CXCR3+ cells were measured by FACS.ResultsIn 229 HCV patients serum IP-10 levels correlated positively to DPPIV serum activity. Higher IP-10 levels and DPPIV activity were detected in cholestatic and in cirrhotic HCV patients. Increased IP-10 serum levels were associated with therapeutic non-response to antiviral treatment with pegylated-interferon and ribavirin. In the HCV FU cohort elevated IP-10 serum levels and increased BA were associated with higher frequencies of peripheral CD3+CXCR3+, CD4+CXCR3+ and CD8+CXCR3+ T cells. Positive correlation between serum IP-10 levels and DPPIV activity was likewise validated in patients with cholestatic liver diseases.ConclusionsA strong correlation between elevated serum levels of IP-10 and DPPIV activity was seen in different cholestatic patient groups. Furthermore, in cholestatic HCV patients a functional link to increased numbers of peripheral CXCR3+ immune cells could be observed. The source of DPPIV release in cholestatic patients remains open.