title: Development and specificities of anti-interferon neutralizing antibodies in patients with chronic hepatitis C treated with pegylated interferon-α.
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.
authors.affiliation: Department of Molecular Medicine, Laboratory of Virology, Sapienza University of Rome, Rome, Italy. carolina.scagnolari@uniroma1.it
authors.forename: C
authors.initials: C
authors.lastname: Scagnolari
authors.forename: S
authors.initials: S
authors.lastname: Trombetti
authors.forename: A
authors.initials: A
authors.lastname: Soldà
authors.forename: M
authors.initials: M
authors.lastname: Milella
authors.forename: G B
authors.initials: GB
authors.lastname: Gaeta
authors.forename: G
authors.initials: G
authors.lastname: Angarano
authors.forename: G
authors.initials: G
authors.lastname: Scotto
authors.forename: N
authors.initials: N
authors.lastname: Caporaso
authors.forename: F
authors.initials: F
authors.lastname: Morisco
authors.forename: R
authors.initials: R
authors.lastname: Cozzolongo
authors.forename: G
authors.initials: G
authors.lastname: Giannelli
authors.forename: M
authors.initials: M
authors.lastname: Fasano
authors.forename: T
authors.initials: T
authors.lastname: Santantonio
authors.forename: G
authors.initials: G
authors.lastname: Antonelli
mesh_terms: D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000998:Antiviral Agents / Q000276:immunology / Q000627:therapeutic use; D016009:Chi-Square Distribution; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000276:immunology* / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use
chemical_list: D057134:Antibodies, Neutralizing; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a