Characterization of Anti-HCV Antibodies in IL-10-Treated Patients

Abstract

There is limited information on the direct role of the neutralizing antibody responses against hepatitis C virus (HCV) infection or methodologies to study them. Previously we have demonstrated that interleukin-10 (IL-10) administered to chronic hepatitis patients led to a decrease in disease activity, but an increase in HCV viral burden. The mechanism behind this is unknown. The objective of this study was to examine the antibody response in IL-10-treated patients. To establish a neutralization antibody assay, HCV-positive and HCV-negative sera were collected and incubated with HCV strain JFH-1 particles before culture with Huh 7.5 cells. Viral replication was measured a week later by either indirect immunofluorescence assay (iIFA) or real-time reverse transcriptase polymerase chain reaction (RT-PCR). After validation of the methodology, the sera from 30 previously-described subjects of a group previously treated with IL-10 were tested for the neutralization capacity of their antibodies. The amount of total anti-HCV antibody in the sera was also measured by direct staining of HCV full-length replicon cells. With this validated neutralization assay for anti-HCV antibodies we found that HCVneutralizing antibodies are universally present, but with significantly different titers. In patients who were treated with IL-10, the total anti-HCV antibody titers appear to be constant, but with significantly decreased antibody neutralization activity. Our study validates an assay to quantitatively determine the presence and strength of HCV-specific neutralizing antibodies. We have found that IL-10-treated patients have significantly lower HCV antibodies, but maintain the total anti-HCV antibody titer, suggesting a novel mechanism by which IL-10 treatment increases viral load in patients.

Inflamed gut mucosa: downstream of interleukin‐10

“…The potent anti‐inflammatory properties of IL‐10 made it appealing to study its therapeutic implications in various human diseases. These include the following: psoriasis [129], wound healing [130], rheumatoid arthritis [131], sepsis [132,133], organ transplantation [134,135], visceral and limb ischaemia [136], atherosclerosis [137], chronic Hepatitis C [138,139], HIV infection [140], post‐ERCP pancreatitis [141], coeliac disease [142] and IBDs [143], especially CD. The first therapeutic administration of recombinant human IL‐10 (rhuIL‐10) back in the mid‐1990s raised hope for a potential treatment option in CD [144].…”

The dynamics of HCV-specific antibody responses in HIV/HCV patients on long-term antiretroviral therapy

“…The establishment of a cell-culture system for HCV has allowed evaluation of antibodies that can neutralise HCV infection. Neutralising antibody (nAb) can be detected using the HCV genotype 2a strain, JFH-1, in HCV mono-infected patients chronically infected with different HCV genotype [11,12]. HIV co-infection reduced nAb levels in a cross-sectional study [13], but we have found no longitudinal data examining HIV/HCV patients after starting ART.…”