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Series GSE256275 Query DataSets for GSE256275
Status Public on Feb 26, 2024
Title Circulating Monocytes are Predictive and Responsive in Moderate-to-Severe Plaque Psoriasis Subjects Treated with Apremilast
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Monocytes play a critical role in the inflammation associated with psoriasis, and their abnormalities have been reported as biomarkers of cardiovascular event risk, a psoriasis comorbidity. Monocytic cells in chronic inflammatory disorders express elevated levels of cAMP phosphodiesterase. Restoring cAMP levels using the oral cAMP phosphodiesterase-4 inhibitor, apremilast, improves clinical outcomes for a subset of psoriasis patients. We asked whether aberrant monocyte subsets or transcriptomic pathways can function as biomarkers of psoriasis endotypes that can predict enhanced clinical responses to cAMP phosphodiesterase inhibition. A 16-week open-label study of 22 patients with monocyte flow cytometric and transcriptomic analysis was performed. Subjects with elevated hyper-adhesive monocyte doublets at baseline were more likely to be responders to apremilast (p< 0.0001); 82% of subjects with elevated hyper-adhesive monocyte doublets achieved 50% reduction in PASI (PASI50) compared to 46% in those without elevated doublets. We observed a significant reduction in hyper-adhesive monocyte-containing doublets and monocyte-platelet aggregates, suggesting an effect of apremilast on the adhesiveness of blood monocytes during chronic inflammation. Monocyte differentially-expressed gene transcripts predictive of clinical response uncovered pharmaco-endotypes with distinct patterns of nucleotide metabolism, energetics, and differentiation. Further study to understand the basis of drug responsiveness, and to develop an apremilast psoriasis treatment algorithm using monocyte refined gene expression is required to validate and become practical in clinical use, offering patients a test that personalizes their likelihood of clinical response.
 
Overall design To examine CD14+ monocyte gene expression in moderate-to-severe plaque psoriasis patients based on response to apremilast.
 
Contributor(s) Larson EL, DeMeo DP, McCormick TS, Cooper KD
Citation(s) 38431222
Submission date Feb 21, 2024
Last update date Mar 05, 2024
Contact name Thomas S McCormick
E-mail(s) tsm4@case.edu
Phone 2165347970
Organization name Case Western Reserve University
Department Dermatology
Lab McCormick
Street address 2109 Adelbert Rd
City Cleveland
State/province OH
ZIP/Postal code 44106
Country USA
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (11)
GSM8092427 Patient 1, site 1, non-responder, baseline [UH15]
GSM8092428 Patient 2, site 1, non-responder, baseline [UH18]
GSM8092429 Patient 3, site 1, non-responder, baseline [UH19]
Relations
BioProject PRJNA1078849

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
GSE256275_raw_counts.tsv.gz 808.1 Kb (ftp)(http) TSV
SRA Run SelectorHelp
Raw data are available in SRA

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