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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-177674
  • 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 enzymaticBackground & 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.show moreshow less

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Metadaten
Author: Monika RauORCiD, 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
URN:urn:nbn:de:bvb:20-opus-177674
Document Type:Journal article
Faculties:Medizinische Fakultät / Medizinische Klinik und Poliklinik II
Language:English
Parent Title (English):PLoS ONE
Year of Completion:2018
Volume:13
Issue:12
Pagenumber:e0208225
Source:PLoS ONE 13(12): e0208225 (2018). DOI: 10.1371/journal.pone.0208225
DOI:https://doi.org/10.1371/journal.pone.0208225
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:T cells; bile; chemokines; cirrhosis; cytotoxic T cells; hepatitis C virus; immune cells; liver diseases
Release Date:2019/04/12
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2018
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International