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

• Published in: PloS one Vol. 13; no. 12; p. e0208225
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03-12-2018; Public Library of Science (PLoS)
• Subjects: Antigens; Antiviral agents; Bile; Bile acids; Bile Acids and Salts - blood; Biological response modifiers; Biology and life sciences; CD26 antigen; CD3 antigen; CD3 Complex - metabolism; CD4 antigen; CD4 Antigens - metabolism; CD8 antigen; Cell adhesion & migration; Chemokine CXCL10 - blood; Chemokines; Cholestasis - blood; Cholestasis - metabolism; Chronic infection; Clinical medicine; Correlation; CXCR3 protein; Dipeptidyl Peptidase 4 - blood; Dipeptidyl-peptidase IV; Dosage and administration; Drug therapy; Enzyme-Linked Immunosorbent Assay; Enzymes; Female; Flow Cytometry; Gallbladder diseases; Gastroenterology; Genotypes; Hepatitis; Hepatitis C; Hepatitis C - blood; Hepatitis C - metabolism; Hepatitis C virus; Hepatocytes; Hepatology; Hospitals; Humans; Immune system; Immunology; Infection; Infectious diseases; Interferon; IP-10 protein; Laboratories; Leukocytes, Mononuclear - metabolism; Liver; Liver cirrhosis; Liver diseases; Lymphocytes; Lymphocytes T; Male; Medical research; Medicine; Medicine and health sciences; Patients; Polymorphism; Proteases; Proteins; Receptors, CXCR3 - metabolism; Rheumatology; Ribavirin; Risk factors; Serum levels; T cells; T-Lymphocytes - metabolism; Viruses; γ-Interferon; Switzerland; Germany; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0208225

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.
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.
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.
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.