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.
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Authors | 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 |
Journal | PloS one
(PLoS One)
Vol. 13
Issue 12
Pg. e0208225
( 2018)
ISSN: 1932-6203 [Electronic] United States |
PMID | 30507970
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Bile Acids and Salts
- CD3 Complex
- CD4 Antigens
- CXCL10 protein, human
- CXCR3 protein, human
- Chemokine CXCL10
- Receptors, CXCR3
- DPP4 protein, human
- Dipeptidyl Peptidase 4
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Topics |
- Bile Acids and Salts
(blood)
- CD3 Complex
(metabolism)
- CD4 Antigens
(metabolism)
- Chemokine CXCL10
(blood)
- Cholestasis
(blood, metabolism)
- Dipeptidyl Peptidase 4
(blood)
- Enzyme-Linked Immunosorbent Assay
- Female
- Flow Cytometry
- Hepatitis C
(blood, metabolism)
- Humans
- Leukocytes, Mononuclear
(metabolism)
- Male
- Receptors, CXCR3
(metabolism)
- T-Lymphocytes
(metabolism)
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