title: The IgG subclass-specificities of anti-IFNbeta antibodies change with time and differ between the IFNbeta products in relapsing remitting multiple sclerosis patients.
abstract: Anti-Interferon beta (IFNbeta) antibodies are frequently produced during treatment with IFNbeta in Multiple Sclerosis (MS) patients. In recent years, it has become clear that these antibodies cause a decrease in IFNbeta-induced biomarkers and in IFNbeta clinical efficacy. Anti-IFNbeta antibodies are mainly of the IgG isotype, which consists of 4 subclasses. In this study, we tested whether changes occurred in IgG subclasses over time. A series of sera from 21 IFNbeta-treated patients (11 IFNbeta-1a, 10 IFNbeta-1b) were analysed longitudinally using a capture ELISA. IFNbeta-1a treated patients had a restricted subclass distribution, whilst IFNbeta-1b-treated patients demonstrated a wider distribution. When compared to IFNbeta-1b-treated patients, IFNbeta-1a-treated patients had lower levels of total and subclass-specific IgGs against IFNbeta. In particular, antibody levels were markedly lower in the neutralizing antibody (NAb) negative (-) category of IFNbeta-1a-treated patients in comparison to the NAb-IFNbeta-1b-treated patients. The most striking observation of this study were the very low levels or complete absence of IgG3 subclass-specific antibodies to IFNbeta in IFNbeta-1a-treated patients. This difference in the levels of IgG3 may help to clarify the differences in the overall pattern of development of anti-IFNbeta antibodies in IFNbeta-1a-and IFNbeta-1b-treated patients.
authors.affiliation: Neuro-Immunology Laboratory, Department of Medicine, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, Canada. ebgibbs@interchange.ubc.ca
authors.forename: Ebrima
authors.initials: E
authors.lastname: Gibbs
authors.forename: Joel
authors.initials: J
authors.lastname: Oger
mesh_terms: D000906:Antibodies / Q000097:blood / Q000145:classification / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification / Q000276:immunology*; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000276:immunology* / Q000494:pharmacology* / Q000627:therapeutic use; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D013997:Time Factors