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Series GSE185047 Query DataSets for GSE185047
Status Public on Oct 08, 2021
Title IFN-α kinoid in systemic lupus erythematosus: Affymetrix Data
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Objective: To evaluate the efficacy and safety of the immunotherapeutic vaccine interferon-α kinoid (IFN-K) in a 36-week (W) phase IIb, randomised, double-blind, placebo (PBO)-controlled trial in adults with active systemic lupus erythematosus (SLE) despite standard of care.
Methods: Patients with SLE (185) with moderate to severe disease activity and positive interferon (IFN) gene signature were randomised to receive IFN-K or PBO intramuscular injections (days 0, 7 and 28 and W12 and W24). Coprimary endpoints at W36 were neutralisation of IFN gene signature and the BILAG-Based Composite Lupus Assessment (BICLA) modified by mandatory corticosteroid (CS) tapering.
Results: IFN-K induced neutralising anti-IFN-α2b serum antibodies in 91% of treated patients and reduce the IFN gene signature (p<0.0001). Modified BICLA responses at W36 did not statistically differ between IFN-K (41%) and PBO (34%). Trends on Systemic Lupus Erythematosus Responder Index-4, including steroid tapering at W36, favoured the IFN- K and became significant (p<0.05) in analyses restricted to patients who developed neutralising anti-IFN-α2b antibodies. Attainment of lupus low disease activity state (LLDAS) at W36 discriminated the two groups in favour of IFN-K (53% vs. 30%, p=0.0022). A significant CS sparing effect of IFN-K was observed from W28 onwards, with a 24% prednisone daily dose reduction at W36 in IFN-K compared with PBO (p=0.0097). The safety profile of IFN-K was acceptable.
Conclusions: IFN-K induced neutralising anti-IFN-α2b antibodies and significantly reduced the IFN gene signature with an acceptable safety profile. Although the clinical coprimary endpoint was not met, relevant secondary endpoints were achieved in the IFN-K group, including attainment of LLDAS and steroid tapering.
Trial registration number NCT02665364.
 
Overall design 185 patients with active SLE with a positive IFN gene signature were randomised, with 93 assigned to PBO and 92 to IFN-K. At randomisation (D0) and W12, W24 and W36, the IFN gene signature, including the 21 IFN-regulated genes, was evaluated by Affymetrix. This was done on 177 patients, among which 169 have completed all visits until W36. RNA was extracted, quality assessed, labelled, hybridised to GeneChip human genome U133 Plus 2.0 arrays, washed, stained and scanned using GeneChip Scanner 3000 7G. Affymetrix CEL files were uploaded to Affymetrix Expression Console software V.1.4.1. Analysis and Robust multichip Analysis normalisation of raw data were performed per batch, and raw dataset was normalised at once.
 
Contributor(s) Houssiau FA, Thanou A, Croughs T, Tee ML
Citation(s) 31871140
Submission date Sep 29, 2021
Last update date Oct 08, 2021
Contact name Frédéric A HOUSSIAU
E-mail(s) frederic.houssiau@uclouvain.be
Phone +3227645391
Organization name Université catholique de Louvain
Department Institut de recherche expérimentale et clinique (IREC)
Lab Pôle de Pathologies rhumatismales (RUMA)
Street address Avenue Hippocrate 10
City Brussels
ZIP/Postal code 1200
Country Belgium
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (704)
GSM5603881 Whole blood, healthy individual, no treatment 1
GSM5603882 Whole blood, healthy individual, no treatment 2
GSM5603883 Whole blood, healthy individual, no treatment 3
Relations
BioProject PRJNA767451

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE185047_RAW.tar 3.4 Gb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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