1328 Dysregulation of circadian clocks in psoriasis

The circadian clock is a group of oscillatory auto-regulatory transcription factors which give rise to rhythms gene expression and enable alignment cellular function with the environment. Human skin has robust psoriasis influenced by rhythms. However, it remains unknown whether genes are dysregulated in lesional skin. We analyzed timestamped transcriptomic data from PSORT (Psoriasis Stratification Optimize Relevant Therapy) consortium compare differentially expressed between morning afternoon (c-DEGs; q.value <0.05 fold change ≥1.5) lesional(LS) non-lesional(NLS) Across discovery replication cohorts, 113 patients provided baseline LS NLS biopsies. Biopsies taken before 10:00 AM (21 LS, 21 NLS) or after 2:00 PM (20 20 were selected for analysis. In NLS, there 65 c-DEGs. 38% these (25/65) recognized rhythmic described other tissues 40% (26/65) not previously time day associated any tissue. Notably, systems analysis, using Ingenuity Pathway Analysis(IPA), identified rhythm as top pathway. There was decreased core CIART, PER1 NR1D1 increased antiphase ARNTL CRY1 compared morning. contrast, only five c-DEGs, one novel c-DEG Expression morning, but unlike significantly increased. Correlation matrices showed that closely resembled normal healthy skin, whereas appeared be disrupted (Mantel Z-score 36.9 27.4 vs reference data). These findings provide evidence whilst maintained non-lesional dysregulated.