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Series GSE139940 Query DataSets for GSE139940
Status Public on Mar 01, 2021
Title Tofacitinib modulates cardiometabolic and immunologic disease markers associated with premature atherosclerosis in SLE
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Increased risk of premature cardiovascular disease (CVD) is well recognized in systemic lupus erythematosus (SLE) and significantly contributes to morbidity and mortality. To date, no pharmacologic intervention has shown to reduce CV risk in SLE. Dysregulation of innate immune responses, including aberrant type I-Interferon (IFN)-neutrophil interactions, has been proposed to significantly contribute to enhanced CV risk in SLE. In lupus animal models, the Janus kinase/signal transducers and activators of transcription (JAK/STAT) inhibitor tofacitinib improves clinical features, immune dysregulation and vascular dysfunction. We hypothesized that JAK/STAT inhibition in SLE subjects would result in amelioration of cardiometabolic and immunologic parameters previously associated with enhanced CVD risk.
Overall design We conducted a phase 1b/2a randomized, double-blind, placebo-controlled clinical trial of oral tofacitinib, 5 mg twice daily, in 30 SLE subjects (2:1 drug to placebo ratio) with mild to moderate disease activity Patients were stratified by the presence or absence of the STAT4 risk allele, previously shown to be associated with more severe SLE Study duration was 84 days, with 56 days of active treatment followed by 28 days off drug We performed, non-invasive assessment of vascular function, measurements of cardiometabolic parameters, quantification of peripheral blood immune cell subsets by flow cytometry and gene expression by whole blood RNA sequencing, quantification of circulating neutrophil extracellular trap (NET) complexes and STAT phosphorylation (pSTAT) in immune cells Adverse events (AEs) were recorded as were assessments of lupus clinical disease activity
Contributor(s) Hasni SA, Kaplan MJ, Brooks SR
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Submission date Nov 05, 2019
Last update date Mar 01, 2021
Contact name Stephen R Brooks
Organization name NIAMS/NIH
Department Biodata Mining and Discovery Section
Street address 50 SOUTH DR, RM 1140
City Bethesda
State/province MD
ZIP/Postal code 20814
Country USA
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (90)
GSM4150250 JAK00001 Placebo Day 1
GSM4150251 JAK00001 Placebo Day 56
GSM4150252 JAK00001 Placebo Day 84
BioProject PRJNA587698
SRA SRP228587

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Supplementary file Size Download File type/resource
GSE139940_180821_lupus_RNA-seq_results.gene.ANOVA.d1.TOFAvsPLACEBO.xlsx 2.3 Mb (ftp)(http) XLSX
GSE139940_180821_lupus_RNA-seq_results.gene.ANOVA.d56.TOFAvsPLACEBO_10-5-18.xlsx 2.9 Mb (ftp)(http) XLSX
GSE139940_180821_lupus_RNA-seq_results.gene.ANOVA.d84.TOFAvsPLACEBO.xlsx 2.3 Mb (ftp)(http) XLSX
GSE139940_180821_lupus_RNA-seq_results.gene.PTT.placebo.1vs56.xlsx 2.6 Mb (ftp)(http) XLSX
GSE139940_180821_lupus_RNA-seq_results.gene.PTT.placebo.1vs84.xlsx 3.3 Mb (ftp)(http) XLSX
GSE139940_180821_lupus_RNA-seq_results.gene.PTT.placebo.56vs84.xlsx 2.6 Mb (ftp)(http) XLSX
GSE139940_180821_lupus_RNA-seq_results.gene.PTT.tofa.1vs56.xlsx 2.6 Mb (ftp)(http) XLSX
GSE139940_180821_lupus_RNA-seq_results.gene.PTT.tofa.1vs84.xlsx 2.8 Mb (ftp)(http) XLSX
GSE139940_180821_lupus_RNA-seq_results.gene.PTT.tofa.56vs84.xlsx 2.6 Mb (ftp)(http) XLSX
GSE139940_180821_lupus_RNA-seq_results.gene.rpkm.xlsx 19.3 Mb (ftp)(http) XLSX
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