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Series GSE88884 Query DataSets for GSE88884
Status Public on Oct 25, 2016
Title Gene expression changes in baseline SLE patients vs. healthy controls from two phase III trials (ILLUMINATE-1 and ILLUMINATE-2) of B cell activating factor blockade with tabalumab
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Objective: Systemic lupus erythematosus (SLE) has substantial unmet medical need and its pathogenesis is incompletely understood. This study characterized baseline gene expression and pharmacodynamic (PD)-induced changes in whole blood gene expression from two phase III, 52-week (W), randomized, placebo-controlled, double-blind studies of 1,760 SLE patients treated with the B cell activating factor (BAFF)-blocking IgG4 monoclonal antibody, tabalumab. Methods: Patient samples were obtained from ILLUMINATE-1 and -2 while control samples were from healthy donors. Blood was collected in TempusTM tubes at baseline, W16 and W52. RNA was analyzed using the Affymetrix Human Transcriptome Array 2.0 and NanoStringTM. Results: At baseline there was elevation of interferon responsive genes (IRG) in patients compared to controls, with 75% positive for this IRG signature. There was, however, substantial heterogeneity of IRG expression and complex relationships among gene networks. The interferon signature was a predictor of future time to flare, independent of anti-double stranded DNA antibody (dsDNA), C3 and C4 levels, and overall disease activity. PD changes in gene expression following tabalumab treatment were extensive, occurring predominantly in B cell-related and immunoglobulin (Ig) genes, and were consistent with other PD-induced changes including dsDNA, C3, and Ig levels. Conclusions: SLE patients demonstrated elevated expression of an IRG signature, detected in 75% of the patients at baseline in ILLUMINATE-1 and -2. There was substantial heterogeneity of gene expression detected among individual patients and in gene networks. The interferon signature was an independent risk factor for future flares. PD changes in gene expression were consistent with the mechanism of BAFF blockade by tabalumab.
 
Overall design 1760 SLE patients at baseline from ILLUMINATE 1 (n=879) and ILLUMINATE 2 (n=881) were compared to 60 healthy controls for differential gene expression.
 
Contributor(s) Hoffman RW, Dow ER, Perumal NB
Citation(s) 27723281, 31790472
Submission date Oct 18, 2016
Last update date Dec 31, 2019
Contact name Robert W Hoffman
E-mail(s) hoffman_robert_w@lilly.com
Phone 1 317 651 4209
Organization name Eli Lilly and Company
Department Lilly Bio-Medicines/Immunology
Street address Lilly Corporate Center
City Indianapolis
State/province IN
ZIP/Postal code 46285
Country USA
 
Platforms (1)
GPL17586 [HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version]
Samples (1820)
GSM2350873 SUBJ.1307, Normal, baseline
GSM2350874 SUBJ.1378, Normal, baseline
GSM2350875 SUBJ.1280, Normal, baseline
This SubSeries is part of SuperSeries:
GSE88887 Gene expression and pharmacodynamic-induced changes in 1760 SLE Patients from two phase III trials of B cell activating factor blockade with tabalumab
Relations
BioProject PRJNA350547

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
GSE88884_ILLUMINATE1and2_SLEbaselineVsHealthy_preprocessed.txt.gz 1.2 Gb (ftp)(http) TXT
GSE88884_RAW.tar 42.1 Gb (http)(custom) TAR (of CEL)
Processed data are available on Series record
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