Immunoglobulin G1 and immunoglobulin G4 antibodies in multiple sclerosis patients treated with IFNβ interact with the endogenous cytokine and activate complement
Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 148(2013), 2 vom: 15. Aug., Seite 177-85 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2013
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Anti-drug antibody; Complement Immunogenicity; Interferon beta; Neutralising antibody; Relapsing-remitting multiple sclerosis; Cytokines Immunoglobulin G mehr... |
| Zusammenfassung: | Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved. 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 |
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| Beschreibung: | Date Completed 17.09.2013 Date Revised 21.10.2021 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2013.05.008 |