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

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• 作者：Swaminathan Sethu ; Karthik Govindappa ; Paul Quinn ; Meenu Wadhwa ; Richard Stebbings ; Mike Boggild ; Dean Naisbitt ; Ian Kimber ; Munir Pirmohamed ; Kevin Park ; Jean Sathish
• 关键词：Interferon beta ; Relapsing-remitting multiple sclerosis ; Immunogenicity ; Anti-drug antibody ; Neutralising antibody ; Complement
• 刊名：Clinical Immunology
• 出版年：2013
• 出版时间：August, 2013
• 年：2013
• 卷：148
• 期：2
• 页码：177-185
• 全文大小：824 K

文摘

A subset of patients with relapsing-remitting multiple sclerosis (RRMS) on therapy with interferon beta (IFN¦Â) develop neutralising anti-drug antibodies (ADA) resulting in reduced, or loss of, therapeutic efficacy. The aims were to characterise the relative contributions of anti-IFN¦Â antibody isotypes to drug neutralising activity, ability of these antibodies to cross-react with endogenous IFN¦Â, to form immune complexes and activate complement. IFN¦Â-specific ADA were measured in plasma from RRMS patients treated with IFN¦Â1a (Rebif^?). Neutralisation of endogenous and therapeutic IFN¦Â by ADA was determined by IFN¦Â bioassay. IFN¦Â-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 IFN¦Â-ADA blocks endogenous IFN¦Â activity. ADA interaction with therapeutic IFN¦Â results in immune complex formation and complement activation. In summary, IgG1 and IgG4 IFN¦Â-ADA have the ability to neutralise therapeutic and endogenous protein and to activate complement.