Characterisation of antibody dependent cellular phagocytosis in patients
infected with Hepatitis C virus with different clinical outcomes
Abstract
Early neutralising antibodies against Hepatitis C virus (HCV) and CD8+T
cell effector responses can lead to viral clearance. However, these
functions alone are not sufficient to protect patients against HCV
infection, thus yet undefined additional anti-viral immune mechanisms
are required. In recent years, Fc-receptor-dependent antibody effector
functions particularly, antibody-dependent cellular phagocytosis (ADCP)
was shown to offer immune protection against several RNA viruses.
However, its development, and clinical role in patients with HCV
infection remain unknown. In this study, we found that patients with
chronic GT1a or GT3a HCV infection had significantly higher
concentrations of anti-envelop 2 (E2) antibodies, predominantly IgG1
subclass, than patients that cleared the viruses while the latter had
antibodies with higher affinities. 97% of the patients with HCV had
measurable ADCP of whom patients with chronic disease showed
significantly higher ADCP than those who naturally cleared the virus.
Epitope mapping studies showed that patients with antibodies that target
antigenic domains on the HCV E2 protein that are known to associate with
neutralisation function also strongly associated with ADCP, suggesting
antibodies with overlapping/dual functions. Correlation studies showed
that ADCP significantly correlated with plasma anti-E2 antibody levels
and neutralisation function regardless of clinical outcome and genotype
of infecting virus while a significant correlation between ADCP and
affinity was only evident in patients that cleared the virus. These
results suggest ADCP was mostly driven by antibody titre in patients
with chronic disease while maintained in clearers due the quality
(affinity) of their anti-E2 antibodies despite having lower antibody
titres.