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.

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...

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Publicado en:Rheumatology Vol. 55; no. 10; pp. 1901 - 1906
Autores principales: Ducreux, Julie, Houssiau, Frédéric A., Vandepapelière, Pierre, Jorgensen, Christian, Lazaro, Estibaliz, Spertini, François, Colaone, Fabien, Roucairol, Camille, Laborie, Marion, Croughs, Thérèse, Grouard-Vogel, Géraldine, Lauwerys, Bernard R.
Formato: pictorial research tables/charts randomized controlled trial Journal Article
Publicado: Oxford University Press / USA Oct2016
Acceso en línea:Ver este registro en EBSCOhost
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      pub: Oxford University Press / USA
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        10.1093/rheumatology/kew262
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        atl: 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.
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        au:
          Ducreux, Julie
          Houssiau, Frédéric A.
          Vandepapelière, Pierre
          Jorgensen, Christian
          Lazaro, Estibaliz
          Spertini, François
          Colaone, Fabien
          Roucairol, Camille
          Laborie, Marion
          Croughs, Thérèse
          Grouard-Vogel, Géraldine
          Lauwerys, Bernard R.
        affil: Institut de Recherche Expérimentale et Clinique, Pôle de pathologies rhumatismales inflammatoires et systémiques, Université catholique de Louvain, Belgium, France
      sug:
        subj:
          Lupus Erythematosus, Systemic Immunology
          Interferons Immunology
          Gene Expression
          B Lymphocytes
          Human
          Randomized Controlled Trials
          Gene Expression Profiling
          Descriptive Statistics
          RNA Analysis
          Adolescence
          Young Adult
          Adult
          Middle Age
          Multicenter Studies
          Data Analysis Software
          Spearman's Rank Correlation Coefficient
          Kruskal-Wallis Test
          Funding Source
          Adolescent: 13-18 years
          Adult: 19-44 years
          Middle Aged: 45-64 years
      ab: 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
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        randomized controlled trial
        Journal Article
      ougenre: Article
    language: English
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