High MIG (CXCL9) plasma levels favours response to peginterferon and ribavirin in HCV-infected patients regardless of DPP4 activity.

Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 101160857 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1478-3231 (Electronic) Linking ISSN: 14783223 NLM ISO Abbreviation: Liver Int Subsets: MEDLINE

Publication: Malden, MA : Wiley-Blackwell
Original Publication: Oxford, UK : Blackwell Munksgaard, c2003-

Antiviral Agents/*therapeutic use ; Chemokine CXCL9/*blood ; Dipeptidyl Peptidase 4/*blood ; Hepatitis C/*drug therapy ; Interferon-alpha/*therapeutic use ; Polyethylene Glycols/*therapeutic use ; Ribavirin/*therapeutic use; Adult ; Black or African American/genetics ; Aged ; Antiviral Agents/adverse effects ; Biomarkers/blood ; Drug Therapy, Combination ; Female ; Genotype ; Hepatitis C/blood ; Hepatitis C/diagnosis ; Hepatitis C/enzymology ; Humans ; Interferon-alpha/adverse effects ; Interferons ; Interleukin-10/blood ; Interleukins/genetics ; Male ; Middle Aged ; Phenotype ; Polyethylene Glycols/adverse effects ; Recombinant Proteins/adverse effects ; Recombinant Proteins/therapeutic use ; Ribavirin/adverse effects ; Time Factors ; Treatment Outcome ; United States ; Up-Regulation ; White People/genetics ; Young Adult

Background & Aims: Sustained virological response (SVR) following peginterferon (pegIFN) and ribavirin (RBV) treatment in hepatitis C virus (HCV)-infected patients has been linked with the IL28B genotype and lower peripheral levels of the CXCR3-binding chemokine IP-10 (CXCL10). To further improve the understanding of these biomarkers we investigated plasma levels of the other CXCR3-binding chemokines and activity of the dipeptidyl peptidase IV (DPP4, CD26) protease, which cleaves IP-10, in relation to treatment response.
Methods: African-American and Caucasian HCV genotype 1-infected patients (n = 401) were treated with pegIFN/RBV for 48 weeks (ViraHep-C cohort). Pretreatment plasma levels of MIG (CXCL9), I-TAC (CXCL11) and the type III interferon IL29 were investigated by Luminex and DPP4 activity by using a luciferase assay.
Results: Patients achieving SVR had higher baseline MIG plasma levels and lower DPP4 activity than non-SVR patients. MIG was higher in Caucasians, IL28B CC (rs1297860) genotype carriers and patients with higher ALT levels. MIG correlated with IP-10 in SVR patients, but not in non-SVRs. A high DPP4 activity correlated with higher IP-10 levels, while DPP4 activity was not associated with MIG or I-TAC levels.
Conclusions: The associations of MIG with SVR status and IL28B genotype imply that higher MIG plasma levels could reflect a beneficial immunological state for response to pegIFN/RBV treatment. The correlation between MIG and IP-10 observed only in SVR patients may contribute to a better treatment response, whereas this MIG/IP-10 balance might be disrupted in non-SVR patients because of the increased DPP4 cleavage of IP-10 into a dysfunctional form.
(© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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K24 DK066144 United States DK NIDDK NIH HHS; P30 CA016086 United States CA NCI NIH HHS

Keywords: DPP4; HCV; IP-10; Interferon; MIG

0 (Antiviral Agents)
0 (Biomarkers)
0 (CXCL9 protein, human)
0 (Chemokine CXCL9)
0 (interferon-lambda, human)
0 (IL10 protein, human)
0 (Interferon-alpha)
0 (Interleukins)
0 (Recombinant Proteins)
130068-27-8 (Interleukin-10)
3WJQ0SDW1A (Polyethylene Glycols)
49717AWG6K (Ribavirin)
9008-11-1 (Interferons)
EC 3.4.14.5 (DPP4 protein, human)
EC 3.4.14.5 (Dipeptidyl Peptidase 4)
Q46947FE7K (peginterferon alfa-2a)

Date Created: 20150908 Date Completed: 20161213 Latest Revision: 20231213

20240829

PMC4744814

10.1111/liv.12932

26344576