393 A trial to determine the effect of psoriasis treatment (adalimumab, phototherapy, and placebo) on cardiometabolic disease: The vascular inflammation in psoriasis (VIP) trial

Abstract

Psoriasis is a common chronic inflammatory skin disease, affecting 2-4% of world population. MicroRNAs (miRNAs) are short non-coding RNAs that regulate expression of the majority of protein-coding genes. In psoriasis, previous studies have identified deregulation in miRNA expression. Most of these studies utilized full-depth skin biopsies and thus may have missed the cell-specific miRNomic signature. Here, we analyzed the miRNome of CD45 neg sorted epidermal cells from psoriasis patients and healthy skin by next-generation sequencing. We detected, differential expression of 104 miRNAs in the psoriatic epidermal cells, including several known and novel miRNAs. MiR-149 was identified as one of the significantly downregulated miRNAs, and qPCR analysis confirmed its downregulation in psoriatic lesional epidermal cells as compared to non-lesional or normal skin. In primary human keratinocytes and in 3D epidermal equivalents, miR-149 was significantly downregulated by IFN-g. Overexpression of miR-149 suppressed the IFN-induced expression of IL-6 as well as T-cell attracting chemokines, while inhibition of endogenous miR-149 led to increased induction of these mediators. Taken together, we have characterized the cell-specific miRNome of epidermal non-immune cells in psoriasis skin and identified epidermal miRNAs, previously not associated with psoriasis. MiR-149 has been identified as a miRNA regulating the response of keratinocytes to IFN-g. Our results can provide a basis for further functional studies of miRNAs in keratinocytes and lead to the identification of potential targets for topical therapy in psoriasis.

Assessing the relative efficacy of interleukin-17 and interleukin-23 targeted treatments for moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis of PASI response

“…Eighty-three RCTs (reported in 127 articles) were included in the SR and 77 (including 34,816 patients) in the NMA. The trials not included in the NMA did not provide results at all [55–57] or in an appropriate format [58], or included a comparator that would not connect relevant interventions in the network [59, 60].…”

Potential Immunological Links Between Psoriasis and Cardiovascular Disease

“…As such, the emerging field of biologic treatments is exciting as it may provide therapeutic utility in psoriasis with added benefits of modulating CVD risk. Furthermore, completed and ongoing trials assessing the subclinical CVD in psoriasis have demonstrated promising findings ( 143 , 144 ).…”

Commentary: Does biologic treatment of psoriasis lower the risk of cardiovascular events and mortality?

“…However, the study does add to a growing literature of observational studies in rheumatoid arthritis and psoriasis suggesting that TNFi are associated with a reduction in CV events 5 . In contrast, two recent, well powered RCTs demonstrated no benefit of TNFi on aortic vascular inflammation, however, important inflammatory CV risk biomarkers such as CRP and GlycA were strongly improved providing some experimental evidence of the potential benefit of TNFi on CV events 6, 7 . Critically, a recent randomized placebo controlled trial (CANTOS) of canakinumab, a biologic targeting Il-1 beta, in 10,061 patients with prior MI and elevated CRP demonstrated, for the first time, that immune targeted treatment causes a reduction in major CV events.…”