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

作者：Johansson Susanne; Talloen Willem; Tuefferd Marianne; Darling Jama; Fanning Gregory; Fried Michael W; Aerssens Jeroen^*

来源：Liver International, 2016, 36(3): 344-352.

DOI：10.1111/liv.12932

• DPP4
• HCV
• Interferon
• IP-10
• MIG

Background & AimsSustained 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.
MethodsAfrican-American and Caucasian HCV genotype 1-infected patients (n=401) were treated with pegIFN/RBV for 48weeks (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.
ResultsPatients achieving SVR had higher baseline MIG plasma levels and lower DPP4 activity than non-SVR patients. MIG was higher in Caucasians, IL28BCC (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.
ConclusionsThe 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.

• 出版日期2016-3