Serum IP-10 levels and increased DPPIV activity are linked to circulating CXCR3+ T cells in cholestatic HCV patients
Rau M, Schmitt J, Berg T, Kremer A, Stieger B, Spanaus K, Bengsch B, Romero MR, Marin JJ, Keitel V, Klinker H, Tony HP, Mullhaupt B, Geier A (2018)
Publication Type: Journal article
Publication year: 2018
Journal
Book Volume: 13
Journal Issue: 12
DOI: 10.1371/journal.pone.0208225
Abstract
BACKGROUND & AIMS: Serum 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. METHODS: In 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. RESULTS: In 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. CONCLUSIONS: A 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.
Authors with CRIS profile
Involved external institutions
Universitätsklinikum Würzburg
Germany (DE)
Universitätsklinikum Leipzig
Germany (DE)
Universitätsspital Zürich (USZ)
Switzerland (CH)
Universitätsklinikum Freiburg
Germany (DE)
University of Salamanca / Universidad de Salamanca
Spain (ES)
Heinrich-Heine-Universität Düsseldorf
Germany (DE)
Germany (DE)
Universitätsklinikum Leipzig
Germany (DE)
Universitätsspital Zürich (USZ)
Switzerland (CH)
Universitätsklinikum Freiburg
Germany (DE)
University of Salamanca / Universidad de Salamanca
Spain (ES)
Heinrich-Heine-Universität Düsseldorf
Germany (DE)
How to cite
APA:
Rau, M., Schmitt, J., Berg, T., Kremer, A., Stieger, B., Spanaus, K.,... Geier, A. (2018). Serum IP-10 levels and increased DPPIV activity are linked to circulating CXCR3+ T cells in cholestatic HCV patients. PLoS ONE, 13(12). https://doi.org/10.1371/journal.pone.0208225
MLA:
Rau, Monika, et al. "Serum IP-10 levels and increased DPPIV activity are linked to circulating CXCR3+ T cells in cholestatic HCV patients." PLoS ONE 13.12 (2018).
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