Immunoglobulin G1 and immunoglobulin G4 antibodies in multiple sclerosis patients treated with IFNβ interact with the endogenous cytokine and activate complement

Swaminathan Sethu, Karthik Govindappa, Paul Quinn, Meenu Wadhwa, Richard Stebbings, Mike Boggild, Dean Naisbitt, Ian Kimber, Munir Pirmohamed, Kevin Park, Jean Sathish

    Research output: Contribution to journalArticlepeer-review

    Abstract

    A subset of patients with relapsing-remitting multiple sclerosis (RRMS) on therapy with interferon beta (IFNβ) develop neutralising anti-drug antibodies (ADA) resulting in reduced, or loss of, therapeutic efficacy. The aims were to characterise the relative contributions of anti-IFNβ antibody isotypes to drug neutralising activity, ability of these antibodies to cross-react with endogenous IFNβ, to form immune complexes and activate complement. IFNβ-specific ADA were measured in plasma from RRMS patients treated with IFNβ1a (Rebif®). Neutralisation of endogenous and therapeutic IFNβ by ADA was determined by IFNβ bioassay. IFNβ-ADA profile was predominantly comprised of IgG1 and IgG4 antibody isotypes. The contribution of IgG4-ADA towards neutralising activity was found to be minimal. Neutralising IFNβ-ADA blocks endogenous IFNβ activity. ADA interaction with therapeutic IFNβ results in immune complex formation and complement activation. In summary, IgG1 and IgG4 IFNβ-ADA have the ability to neutralise therapeutic and endogenous protein and to activate complement. © 2013 The Authors.
    Original languageEnglish
    Pages (from-to)177-185
    Number of pages8
    JournalClinical Immunology
    Volume148
    Issue number2
    DOIs
    Publication statusPublished - Aug 2013

    Keywords

    • Anti-drug antibody;
    • Complement
    • Immunogenicity;
    • Interferon beta;
    • Neutralising antibody
    • Relapsing-remitting multiple sclerosis;

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