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is missing (Short communication)

BackgroundMicroRNAs are small regulatory molecules that are dysregulated in psoriasis. Despite previous efforts, much is unknown about the regulatory mechanisms of psoriasis genetics and their contributions to disease development and activity.ObjectivesTo globally characterize the miRNAome of psoriatic skin in a large sample of psoriatic cases and controls for increased understanding of psoriasis pathophysiology.MethodsSkin biopsies from psoriatic cases (n=75) and non-psoriatic controls (n=57) were RNA sequenced. Count data was meta-analyzed with a previously published dataset (cases, n=24, controls, n=20), increasing the number of psoriatic cases four-fold from previously published studies. Differential expression analyses were performed comparing lesional psoriatic (PP), non-lesional psoriatic (PN) and control (NN) skin. Further, functional enrichment and cell specific analyses were performed.ResultsWe identified 439 significantly differentially expressed miRNAs (DEMs), of which 131 were novel and 11 were related to disease severity. Meta-analyses identified 20 DEMs between PN and NN, suggesting an inherent change in all psoriatic skin. By integrating the miRNA transcriptome with mRNA target interactions, we identified several functionally enriched terms, including ‘thyroid hormone signaling’, ‘insulin resistance’ and various infectious diseases. Cell specific expression analyses revealed that the upregulated DEMs were enriched in epithelial and immune cells.ConclusionsWe have provided the most comprehensive overview of the miRNome in psoriatic skin to date and identified a miRNA signature related to psoriasis severity. Our results may represent molecular links between psoriasis and related comorbidities and have outlined potential directions for future functional studies to identify biomarkers and treatment targets.

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Psoriasis has been associated with increased adiposity measures driving systemic inflammation, which may lead to metabolic dysfunction and comorbidities. In this population-based, cross-sectional study, we used data from 56 042 individuals in the fourth wave of the Trøndelag Health Study (HUNT4), to investigate the associations between psoriasis and body composition measures assessed using bioelectrical impedance analysis, cardiometabolic risk factors, and comorbidities. Further, we investigated the associations between HLA-C*06:02 status, a potential clinical biomarker for a distinct psoriasis endotype, and these outcomes. Psoriasis was associated with increased adiposity measures, including increased body and visceral fat, and lower levels of skeletal muscle and soft lean mass, as well as higher prevalences of cardiovascular, respiratory and endocrine disorders. HLA-C*06:02 -positive individuals with psoriasis had lower levels of hsCRP, increased prevalence of atrial fibrillation and decreased prevalence of migraine. Our results point to altered body composition in psoriasis with increased levels of fat, and particularly metabolically active visceral fat, and provide support for a broad clinical approach to psoriatic patients in a general population.