Significant Correlation Between Cutaneous Abundance of Streptococcus and Psoriasis Severity in Patients with FBXL19 Gene Variants.

Psoriasis results from both genetic predisposition and environmental triggers, such as Streptococcal infections. This study aimed to explore the correlation between the abundance of the Streptococcus genus on the skin and psoriasis severity in individuals carrying specific psoriasis-associated genetic variants. Studying 39 chronic plaque psoriasis patients, the elbow skin microbiome and 49 psoriasis-related single nucleotide polymorphisms (SNPs) were analysed using a MiSeq instrument for 16S rDNA sequencing, and CLC Genomic Workbench for processing and analysis. Through multivariate linear regression analysis, a positive correlation was found between Streptococcus genus abundance and psoriasis severity in patients with certain FBXL19 gene-related heterozygous SNPs (rs12924903, rs10782001, rs12445568). Conversely, a negative association was observed in patients with homozygous genotypes. Moreover, we identified an association between Streptococcus abundance and psoriasis severity in patients with genetic variants related to IL-22, ERAP1, NOS2, and ILF3. This is the first study highlighting a positive association between Streptococcus skin colonization and psoriasis severity in patients with heterozygous genotypes within the FBXL19 gene region. FXBL19 targets the IL-33/IL1RL1 axis, crucial in infectious diseases and innate immunity promotion. These novel results suggests an intricate interaction among host genetics, Streptococcus skin colonization, and psoriasis inflammation, offering potential avenues for novel treatment approaches.

Narrowband-UVB treatment reduces levels of mediators of the Th17 pathway and chemotaxis in psoriatic skin without any concurring effect on mediator levels in serum

Background: Narrowband-UVB (NB-UVB) is a common and effective psoriasis treatment. It exerts its effect locally and is therefore a better model for exploring dynamics of serum biomarkers reflecting psoriasis skin disease activity compared to other treatments with systemic uptake. Objectives: To perform an exploratory study to assess potential roles of multiple disease mediators as biomarkers for psoriasis disease activity, and increase understanding of NB-UVB treatment effects in psoriatic skin. Materials & Methods: Patients with plaque psoriasis were sampled (lesional, non-lesional skin, serum) before and after full NB-UVB treatment. Samples were assessed for 78 different mediators using Luminex assays. Correlation networks were analysed to explore interactions between lesional skin mediators before and after NB-UVB treatment. Results: None of the studied serum mediators were significantly affected by NB-UVB treatment after correction for multiple testing. Thirty mediators revealed a significant difference in lesional skin compared to non-lesional skin before treatment including interleukin 23 (IL-23) and C-C motif chemokine ligand 20 (CCL20), but also novel mediators such as angiopoietin-like 4 (ANGPTL4) and pentraxin 3 (PTX3). The levels of 25 mediators in skin decreased significantly, and network analysis revealed markedly reduced cluster formations and correlations after NB-UVB. Conclusion: NB-UVB treatment reduced the concentration of mediators of the Th17 inflammatory pathway and chemotaxis in psoriatic lesional skin, but also affected less studied and novel mediators. Although the treatment affected the levels of a majority of mediators in skin, no corresponding effect was observed in serum, thus challenging the possibility of a serum biomarker reflecting skin disease activity.

Significant Differences in the Bacterial Microbiome of the Pharynx and Skin in Patients with Psoriasis Compared with Healthy Controls.

Studies have shown differences in the skin and gut bacterial microbiomes in patients with psoriasis, but the pharyngeal microbiome has not been studied previously. The aim of this study was to investigate differences in the bacterial microbiome of the pharynx and skin of patients with psoriasis compared with healthy controls. Swabs were taken from the pharynx and elbow skin of 39 patients with psoriasis and 70 controls. Microbiomes were characterized by sequencing 16S rRNA genes on the Illumina MiSeq platform. Significant differences were found in alpha and beta diversity in the skin, but not in the pharynx. Significant differences were also found between several phyla and genera in both skin and pharynx. The severity of psoriasis did not correlate with any genera in the pharynx, but with Capnocytophaga, Leptotrichia, Abiotrophia and Tannerella in the skin. The composition of the pharyn-geal and skin microbiome may be of importance in the patho-genesis of psoriasis.

Narrowband UVB treatment induces expression of WNT7B, WNT10B and TCF7L2 in psoriasis skin.

WNT/ß-catenin signaling pathways play a pivotal role in the human immune defense against infections and in chronic inflammatory conditions as psoriasis. Wnt gene alterations are linked to known comorbidities of psoriasis as obesity, diabetes and Crohn's disease. The objective of this study was to investigate WNT7B, WNT10B, WNT16 and TCF7L2 gene and protein expression in lesional and non-lesional skin and in the peripheral blood of patients with chronic plaque psoriasis compared with healthy individuals. To investigate the effect of narrowband UVB radiation, expression of these genes were analyzed before and after narrowband UVB treatment. Associations between single nucleotide polymorphisms for WNT7B, WNT10B, WNT16 and TCF7L2 genes and psoriasis were tested. Our results show significantly decreased WNT7B, WNT10B and TCF7L2 gene expression in lesional skin compared with non-lesional skin and healthy controls. Narrowband UVB treatment significantly increased expression of these genes in lesional skin. Immunohistochemistry shows increased WNT16 expression in lesional skin. No significant differences in allele or genotype frequencies for Wnt or TCF7L2 gene polymorphisms were found between patient and control group. This study shows for the first time significant UVB induced upregulation of WNT7B, WNT10B and TCF7L2 in patients with psoriasis and suggests a potential role of these genes in psoriasis pathogenesis.

Observational study on Swedish plaque psoriasis patients receiving narrowband-UVB treatment show decreased S100A8/A9 protein and gene expression levels in lesional psoriasis skin but no effect on S100A8/A9 protein levels in serum.

S100A8 and S100A9 proteins are highly upregulated in patients with psoriasis and have been proposed as potential biomarkers for psoriasis. The present study was designed to analyze the effect of narrowband ultraviolet B therapy on these proteins. S100A8, S100A9 gene expression and S100A8/A9 heterocomplex protein levels were analyzed in lesional and non-lesional skin before and after narrowband-UVB treatment in patients with chronic plaque type psoriasis. In addition, disease severity was measured by psoriasis area and severity index (PASI) and serum protein levels of S100A8/A9 were repeatedly analyzed. Narrowband-UVB treatment significantly reduced S100A8, S100A9 gene expression and S100A8/A9 protein levels in lesional skin while serum levels showed no significant change. No correlation between PASI and serum S100A8/A9 protein levels was found. These results implicate a role of S100A8/A9 in the anti-inflammatory effect of narrowband-UVB. Serum S100A8/A9 levels do not respond to treatment suggesting that serum S100A8/A9 does not originate from psoriasis skin keratinocytes. Serum S100A8/A9 levels do not correlate with PASI questioning serum S100A8/A9 as a biomarker for psoriasis skin activity. Trial Registration: DRKS 00014817.

Significant Changes in the Skin Microbiome in Patients with Chronic Plaque Psoriasis after Treatment with Narrowband Ultraviolet B.

Changes in the skin microbiome have been shown to promote cutaneous inflammation. The skin microbiome of patients with chronic plaque type psoriasis was analysed before and after treatment with narrowband ultraviolet B (UVB). Swab samples of the microbiome were taken from lesional and non-lesional skin of 26 patients. Microbiotas were characterized by sequencing 16S rRNA bacterial genes on the Illumina MiSeq platform. Lesional skin microbiome diversity correlated with psoriasis severity (measured with the Psoriasis Area and Severity Index; PASI). There was a significantly lower abundance of the phylum Firmicutes and the genus Staphylococcus in lesional skin compared with non-lesional skin before UVB treatment. Responders (> 75% target Psoriasis Severity Index (PSI) improvement) had significantly lower abundance of the phyla Firmicutes in lesional and non-lesional skin and lower abundance of the genera Staphylococcus, Finegoldia, Anaerococcus, Peptoniphilus, Gardnerella, Prevotella and Clostridium in lesional skin after UVB treatment. Pseudomonas significantly decreased in lesional and non-lesional skin of treatment responders. These results suggest that skin microbiome alterations after UVB treatment could be related to treatment and treatment response.