Document Detail


Down-regulation of interferon signature in systemic lupus erythematosus patients by active immunization with interferon α-kinoid.
MedLine Citation:
PMID:  23203821     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: We developed interferon-α-kinoid (IFN-K), a drug composed of inactivated IFNα coupled to a carrier protein, keyhole limpet hemocyanin. In human IFNα-transgenic mice, IFN-K induces polyclonal antibodies that neutralize all 13 subtypes of human IFNα. We also previously demonstrated that IFN-K slows disease progression in a mouse model of systemic lupus erythematosus (SLE). This study was undertaken to examine the safety, immunogenicity, and biologic effects of active immunization with IFN-K in patients with SLE.
METHODS: We performed a randomized, double-blind, placebo-controlled, phase I/II dose-escalation study comparing 3 or 4 doses of 30 μg, 60 μg, 120 μg, or 240 μg of IFN-K or placebo in 28 women with mild to moderate SLE.
RESULTS: IFN-K was well tolerated. Two SLE flares were reported as serious adverse events, one in the placebo group and the other in a patient who concomitantly stopped corticosteroids 2 days after the first IFN-K dose, due to mild fever not related to infection. Transcriptome analysis was used to separate patients at baseline into IFN signature-positive and -negative groups, based on the spontaneous expression of IFN-induced genes. IFN-K induced anti-IFNα antibodies in all immunized patients. Notably, significantly higher anti-IFNα titers were found in signature-positive patients than in signature-negative patients. In IFN signature-positive patients, IFN-K significantly reduced the expression of IFN-induced genes. The decrease in IFN score correlated with the anti-IFNα antibody titer. Serum complement C3 levels were significantly increased in patients with high anti-IFNα antibody titers.
CONCLUSION: These results show that IFN-K is well tolerated, immunogenic, and significantly improves disease biomarkers in SLE patients, indicating that further studies of its clinical efficacy are warranted.
Authors:
Bernard R Lauwerys; Eric Hachulla; François Spertini; Estibaliz Lazaro; Christian Jorgensen; Xavier Mariette; Edwige Haelterman; Géraldine Grouard-Vogel; Bernard Fanget; Olivier Dhellin; Pierre Vandepapelière; Frédéric A Houssiau
Publication Detail:
Type:  Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  65     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-29     Completed Date:  2013-04-11     Revised Date:  2013-11-14    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  447-56     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 by the American College of Rheumatology.
Affiliation:
Université Catholique de Louvain and Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT01058343
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MeSH Terms
Descriptor/Qualifier:
Adult
Double-Blind Method
Down-Regulation / drug effects*
Female
Gene Expression
Hemocyanin / immunology
Humans
Interferon-alpha / genetics,  immunology*,  therapeutic use*
Lupus Erythematosus, Systemic / drug therapy*,  genetics,  immunology
Middle Aged
Severity of Illness Index
Treatment Outcome
Vaccination / methods*
Chemical
Reg. No./Substance:
0/Interferon-alpha; 9013-72-3/Hemocyanin; FV4Y0JO2CX/keyhole-limpet hemocyanin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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