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

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...

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Autores principales: Rau, Monika, Schmitt, Johannes, Berg, Thomas, Kremer, Andreas E., Stieger, Bruno, Spanaus, Katharina, Bengsch, Bertram, Romero, Marta R., Marin, Jose J., Keitel, Verena, Klinker, Hartwig, Tony, Hans-Peter, Müllhaupt, Beat, Geier, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277069/
https://www.ncbi.nlm.nih.gov/pubmed/30507970
http://dx.doi.org/10.1371/journal.pone.0208225
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author Rau, Monika
Schmitt, Johannes
Berg, Thomas
Kremer, Andreas E.
Stieger, Bruno
Spanaus, Katharina
Bengsch, Bertram
Romero, Marta R.
Marin, Jose J.
Keitel, Verena
Klinker, Hartwig
Tony, Hans-Peter
Müllhaupt, Beat
Geier, Andreas
author_facet Rau, Monika
Schmitt, Johannes
Berg, Thomas
Kremer, Andreas E.
Stieger, Bruno
Spanaus, Katharina
Bengsch, Bertram
Romero, Marta R.
Marin, Jose J.
Keitel, Verena
Klinker, Hartwig
Tony, Hans-Peter
Müllhaupt, Beat
Geier, Andreas
author_sort Rau, Monika
collection PubMed
description 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.
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spelling pubmed-62770692018-12-20 Serum IP-10 levels and increased DPPIV activity are linked to circulating CXCR3+ T cells in cholestatic HCV patients Rau, Monika Schmitt, Johannes Berg, Thomas Kremer, Andreas E. Stieger, Bruno Spanaus, Katharina Bengsch, Bertram Romero, Marta R. Marin, Jose J. Keitel, Verena Klinker, Hartwig Tony, Hans-Peter Müllhaupt, Beat Geier, Andreas PLoS One Research Article 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. Public Library of Science 2018-12-03 /pmc/articles/PMC6277069/ /pubmed/30507970 http://dx.doi.org/10.1371/journal.pone.0208225 Text en © 2018 Rau et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Rau, Monika
Schmitt, Johannes
Berg, Thomas
Kremer, Andreas E.
Stieger, Bruno
Spanaus, Katharina
Bengsch, Bertram
Romero, Marta R.
Marin, Jose J.
Keitel, Verena
Klinker, Hartwig
Tony, Hans-Peter
Müllhaupt, Beat
Geier, Andreas
Serum IP-10 levels and increased DPPIV activity are linked to circulating CXCR3+ T cells in cholestatic HCV patients
title Serum IP-10 levels and increased DPPIV activity are linked to circulating CXCR3+ T cells in cholestatic HCV patients
title_full Serum IP-10 levels and increased DPPIV activity are linked to circulating CXCR3+ T cells in cholestatic HCV patients
title_fullStr Serum IP-10 levels and increased DPPIV activity are linked to circulating CXCR3+ T cells in cholestatic HCV patients
title_full_unstemmed Serum IP-10 levels and increased DPPIV activity are linked to circulating CXCR3+ T cells in cholestatic HCV patients
title_short Serum IP-10 levels and increased DPPIV activity are linked to circulating CXCR3+ T cells in cholestatic HCV patients
title_sort serum ip-10 levels and increased dppiv activity are linked to circulating cxcr3+ t cells in cholestatic hcv patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277069/
https://www.ncbi.nlm.nih.gov/pubmed/30507970
http://dx.doi.org/10.1371/journal.pone.0208225
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