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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State: Public
Version: Final published version
Serval ID
serval:BIB_A36F9251EAEC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
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.
Journal
Rheumatology (Oxford, England)
Author(s)
Ducreux J., Houssiau F.A., Vandepapelière P., Jorgensen C., Lazaro E., Spertini F., Colaone F., Roucairol C., Laborie M., Croughs T., Grouard-Vogel G., Lauwerys B.R.
ISSN
1462-0332 (Electronic)
ISSN-L
1462-0324
Publication state
Published
Issued date
10/2016
Peer-reviewed
Oui
Volume
55
Number
10
Pages
1901-1905
Language
english
Notes
Publication types: Clinical Trial, Phase I ; Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial
Publication Status: ppublish
Abstract
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.
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.
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.
IFN-K induces a polyclonal anti-IFNα response that decreases IFN- and B cell-associated transcripts.
ClinicalTrials.gov, clinicaltrials.gov, NCT01058343.

Keywords
Adolescent, Adult, Anti-Inflammatory Agents/administration & dosage, Antibodies, Neutralizing/immunology, B-Lymphocytes/immunology, Dose-Response Relationship, Drug, Double-Blind Method, Female, Follow-Up Studies, Humans, Interferon-alpha/administration & dosage, Interferon-alpha/immunology, Lupus Erythematosus, Systemic/drug therapy, Lupus Erythematosus, Systemic/immunology, Lymphocyte Activation/immunology, Male, Middle Aged, Recombinant Proteins/administration & dosage, Young Adult
Pubmed
Open Access
Yes
Create date
01/07/2016 9:12
Last modification date
20/08/2019 15:09
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