Immunoglobulin G1 and immunoglobulin G4 antibodies in multiple sclerosis patients treated with IFNß interact with the endogenous cytokine and activate complement.
Clin Immunol
; 148(2): 177-85, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23770627
ABSTRACT
A subset of patients with relapsing-remitting multiple sclerosis (RRMS) on therapy with interferon beta (IFNß) develop neutralising anti-drug antibodies (ADA) resulting in reduced, or loss of, therapeutic efficacy. The aims were to characterise the relative contributions of anti-IFNß antibody isotypes to drug neutralising activity, ability of these antibodies to cross-react with endogenous IFNß, to form immune complexes and activate complement. IFNß-specific ADA were measured in plasma from RRMS patients treated with IFNß1a (Rebif(®)). Neutralisation of endogenous and therapeutic IFNß by ADA was determined by IFNß bioassay. IFNß-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 IFNß-ADA blocks endogenous IFNß activity. ADA interaction with therapeutic IFNß results in immune complex formation and complement activation. In summary, IgG1 and IgG4 IFNß-ADA have the ability to neutralise therapeutic and endogenous protein and to activate complement.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Imunoglobulina G
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Citocinas
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Interferon beta
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Ativação do Complemento
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Fatores Imunológicos
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Esclerose Múltipla
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Reino Unido