Development and specificities of anti-interferon neutralizing antibodies in patients with chronic hepatitis C treated with pegylated interferon-α

Clin Microbiol Infect. 2012 Oct;18(10):1033-9. doi: 10.1111/j.1469-0691.2011.03729.x. Epub 2011 Dec 22.

Abstract

Only limited data are available on the development of neutralizing antibodies (NAB) in patients with chronic hepatitis C (CHC) treated with pegylated interferon-α (PEG-IFN-α). The aim of this study was to evaluate the immunogenicity of PEG-IFN-α when administered to CHC patients who had or had not previously received standard IFN-α therapy. In addition, the specificities of NAB, together with the ability of leucocyte (LE) -IFN-α to re-establish therapeutic responsiveness in NAB-positive patients, were evaluated. NAB were assessed using a quantitative, standardized, virus-induced cytopathic effect assay. The seroconversion rate to PEG-IFN-α was higher in patients who had received previous standard IFN-α treatment than in those treated exclusively with PEG-IFN-α. Also, NAB produced during PEG-IFN-α therapy were unable to neutralize LE-IFN-α entirely, even though they can neutralize several IFN-α subtypes. In addition, the results indicate that a change to LE-IFN-α therapy can be associated with restoration of clinical responses in NAB-positive patients who had become resistant after showing an initial response to PEG-IFN-α treatment. This study emphasizes the importance of evaluating NAB development in CHC patients who become resistant to PEG-IFN-α treatment, and suggests management alternatives for patients who develop NAB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Neutralizing / immunology*
  • Antiviral Agents / immunology
  • Antiviral Agents / therapeutic use
  • Chi-Square Distribution
  • Female
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / immunology*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / immunology*
  • Interferon-alpha / therapeutic use*
  • Logistic Models
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Recombinant Proteins / immunology
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use

Substances

  • Antibodies, Neutralizing
  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2b
  • peginterferon alfa-2a