Interferon α kinoid induces neutralizing anti-interferon α antibodies that decrease the expression of interferon-induced and B cell activation associated transcripts: analysis of extended follow-up data from the interferon α kinoid phase I/II study.
Rheumatology (Oxford)
; 55(10): 1901-5, 2016 Oct.
Article
em En
| MEDLINE
| ID: mdl-27354683
ABSTRACT
OBJECTIVE:
IFN α Kinoid (IFN-K) is a therapeutic vaccine composed of IFNα2b coupled to a carrier protein. In a phase I/II placebo-controlled trial, we observed that IFN-K significantly decreases the IFN gene signature in whole blood RNA samples from SLE patients. Here, we analysed extended follow-up data from IFN-K-treated patients, in order to evaluate persistence of neutralizing anti-IFNα Abs antibodies (Abs), and gene expression profiling.METHODS:
Serum and whole blood RNA samples were obtained in IFN-K-treated patients included in the follow-up study, in order to determine binding and neutralizing anti-IFNα Ab titres, and perform high-throughput transcriptomic studies.RESULTS:
Neutralization studies of 13 IFNα subtypes demonstrated the polyclonal nature of the Ab response induced by IFN-K. Follow-up analyses in six patients confirmed a significant correlation between neutralizing anti-IFNα Ab titres and decrease in IFN scores compared to baseline. These analyses also revealed an inhibitory effect of IFNα blockade on the expression of B cell associated transcripts.CONCLUSIONS:
IFN-K induces a polyclonal anti-IFNα response that decreases IFN- and B cell-associated transcripts. TRIAL REGISTRATION ClinicalTrials.gov, clinicaltrials.gov, NCT01058343.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Linfócitos B
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Interferon-alfa
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Anticorpos Neutralizantes
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Lúpus Eritematoso Sistêmico
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Anti-Inflamatórios
Tipo de estudo:
Clinical_trials
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Observational_studies
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Prognostic_studies
Limite:
Adolescent
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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:
Rheumatology (Oxford)
Assunto da revista:
REUMATOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article