Role of soluble inflammatory mediators and different immune cell populations in early control of symptomatic acute hepatitis C virus infection

TY - JOUR

T1 - Role of soluble inflammatory mediators and different immune cell populations in early control of symptomatic acute hepatitis C virus infection

AU - Hengst, Julia

AU - Klein, Andreas L

AU - Lunemann, Sebastian

AU - Deterding, Katja

AU - Hardtke, Svenja

AU - Falk, Christine S

AU - Manns, Michael P

AU - Cornberg, Markus

AU - Schlaphoff, Verena

AU - Wedemeyer, Heiner

N1 - © 2018 John Wiley & Sons Ltd.

PY - 2019/4

Y1 - 2019/4

N2 - The natural course of acute Hepatitis C Virus (aHCV) infection is highly heterogeneous, and only few biomarkers have been identified to reliably predict the outcome of infection. We analysed a large panel of soluble inflammatory mediators, immune cell frequencies and phenotypes using peripheral blood samples from 26 patients with symptomatic aHCV infection from a controlled randomized clinical trial (ISRCTN88729946, www.isrctn.com). We found that patients with a spontaneous early HCV control demonstrated a distinct expression pattern of various soluble immune mediators including IFNα and IL-16. Immune cell phenotype and frequency differed between patients who cleared the viral infection early (n=13) and those who remained HCV RNA positive after 12 weeks of observation (n=13) with a reduced ratio of CD4+ T cells to NK cells in the non-early clearer. Further, correlation analyses of 50 cytokines and chemokines revealed more positive correlations in between the distinct cytokines, especially for IFNα and IL-16, and between the cytokines and HCV RNA levels in spontaneous early clearer patients. Beyond that, in vitro stimulation of CD4+ T cells with IL-16 reduced the susceptibility of these cells to killing by IFNα-activated NK cells. These data indicate that the immune cell composition and cytokine pattern varies considerably in patients with symptomatic aHCV infection. NK cell-mediated killing of CD4+ T cells might affect early control of HCV infection.

AB - The natural course of acute Hepatitis C Virus (aHCV) infection is highly heterogeneous, and only few biomarkers have been identified to reliably predict the outcome of infection. We analysed a large panel of soluble inflammatory mediators, immune cell frequencies and phenotypes using peripheral blood samples from 26 patients with symptomatic aHCV infection from a controlled randomized clinical trial (ISRCTN88729946, www.isrctn.com). We found that patients with a spontaneous early HCV control demonstrated a distinct expression pattern of various soluble immune mediators including IFNα and IL-16. Immune cell phenotype and frequency differed between patients who cleared the viral infection early (n=13) and those who remained HCV RNA positive after 12 weeks of observation (n=13) with a reduced ratio of CD4+ T cells to NK cells in the non-early clearer. Further, correlation analyses of 50 cytokines and chemokines revealed more positive correlations in between the distinct cytokines, especially for IFNα and IL-16, and between the cytokines and HCV RNA levels in spontaneous early clearer patients. Beyond that, in vitro stimulation of CD4+ T cells with IL-16 reduced the susceptibility of these cells to killing by IFNα-activated NK cells. These data indicate that the immune cell composition and cytokine pattern varies considerably in patients with symptomatic aHCV infection. NK cell-mediated killing of CD4+ T cells might affect early control of HCV infection.

U2 - 10.1111/jvh.13050

DO - 10.1111/jvh.13050

M3 - SCORING: Journal article

C2 - 30548086

VL - 26

SP - 466

EP - 475

JO - J VIRAL HEPATITIS

JF - J VIRAL HEPATITIS

SN - 1352-0504

IS - 4

ER -