Evaluation of ß2-microglobulin in the condition and prognosis of psoriasis patients.

BACKGROUND: Numerous studies have linked the inflammatory pathway in psoriasis and metabolic disease, while no specific marker defined it. It is worth exploring the association of ß2-microglobulin (ß2M) in psoriasis severity and comorbidities. OBJECTIVES: To investigate the correlation between blood ß2M level and psoriasis severity, to explore the inflammatory factors influencing the occurrence of psoriasis comorbidities such as arthritis, diabetes, and hypertension. METHODS: Ninety-seven psoriasis patients were analyzed in the cohort retrospective study during 12 weeks. RESULTS: Significantly higher levels of blood ß2M and ESR were observed in the group that patients' PASI ≥10 than in the group that PASI <10. Blood ß2M level had strong significantly positive correlations with the PASI in Pearson's correlation analysis. In the model that systemic inflammatory factors to find psoriasis comorbidity risk factors, logistic regression analysis showed that blood ß2M level was the significant risk factor associated with diabetes and hypertension. High-sensitivity C-reactive protein (hsCRP) was the significant risk factor associated with arthritis. CONCLUSIONS: Patients with a severer psoriasis tended to have higher blood ß2M levels and severer inflammatory state. In the systemic inflammation indexes, the level of blood ß2M affected the risk of hypertension and diabetes, and hsCRP affected the risk of arthritis in patients with psoriasis.

Exploration of ferroptosis and necroptosis-related genes and potential molecular mechanisms in psoriasis and atherosclerosis.

Objective: Ferroptosis and necroptosis are two recently identified forms of non-apoptotic cell death. Their dysregulation plays a critical role in the development and progression of Psoriasis (PsD) and Atherosclerosis (AS). This study explores shared Ferroptosis and necroptosis-related genes and elucidates their molecular mechanisms in PsD and AS through the analysis of public databases. Methods: Data sets for PsD (GSE30999) and AS (GSE28829) were retrieved from the GEO database. Differential gene expression (DEG) and weighted gene co-expression network analysis (WGCNA) were performed. Machine learning algorithms identified candidate biomarkers, whose diagnostic values were assessed using Receiver Operating Characteristic (ROC) curve analysis. Additionally, the expression levels of these biomarkers in cell models of AS and PsD were quantitatively measured using Western Blot (WB) and real-time quantitative PCR (RT-qPCR). Furthermore, CIBERSORT evaluated immune cell infiltration in PsD and AS tissues, highlighting the correlation between characteristic genes and immune cells. Predictive analysis for candidate drugs targeting characteristic genes was conducted using the DGIdb database, and an lncRNA-miRNA-mRNA network related to these genes was constructed. Results: We identified 44 differentially expressed ferroptosis-related genes (DE-FRGs) and 30 differentially expressed necroptosis-related genes (DE-NRGs). GO and KEGG enrichment analyses revealed significant enrichment of these genes in immune-related and inflammatory pathways, especially in NOD-like receptor and TNF signaling pathways. Two ferroptosis-related genes (NAMPT, ZFP36) and eight necroptosis-related genes (C7, CARD6, CASP1, CTSD, HMOX1, NOD2, PYCARD, TNFRSF21) showed high sensitivity and specificity in ROC curve analysis. These findings were corroborated in external validation datasets and cell models. Immune infiltration analysis revealed increased levels of T cells gamma delta, Macrophages M0, and Macrophages M2 in PsD and AS samples. Additionally, we identified 43 drugs targeting 5 characteristic genes. Notably, the XIST-miR-93-5p-ZFP36/HMOX1 and NEAT1-miR-93-5p-ZFP36/HMOX1 pathways have been identified as promising RNA regulatory pathways in AS and PsD. Conclusion: The two ferroptosis-related genes (NAMPT, ZFP36) and eight necroptosis-related genes (C7, CARD6, CASP1, CTSD, HMOX1, NOD2, PYCARD, TNFRSF21) are potential key biomarkers for PsD and AS. These genes significantly influence the pathogenesis of PsD and AS by modulating macrophage activity, participating in immune regulation, and mediating inflammatory responses.

Increased serum ATG5 as a marker of autophagy in psoriasis vulgaris patients: a cross-sectional study.

Psoriasis (PsO) is a prevalent chronic inflammatory skin disease. It is a complex condition that is affected by environmental and hereditary variables. Numerous pathogens, including viruses, bacteria, and even fungi, have been linked to PsO. One of the mechanisms that clears infections is autophagy. The mechanism by which a cell feeds itself is called autophagy by reusing cytoplasmic components in the lysosome. The autophagy-related (ATG) proteins are essential components of the system that control the strictly regulated process of autophagy. Among these 41 proteins, ATG5 is one that is required in order for autophagic vesicles to develop. This research aimed to compare ATG5 levels in serum among those suffering from psoriasis vulgaris and healthy controls. This cross-sectional research was carried out on 45 individuals with vulgaris psoriasis and 45 healthy, sex and age-matched control subjects. All participants underwent a clinical examination, a laboratory investigation, and a history taking, including lipid profiles and serum ATG5. The mean age of the control and PsO were 40.6 ± 9.6, and 43.7 ± 9.3 years respectively. The mean total PASI score was 13.9 ± 8.9, with a median of 11.7 (8.8). According to the PASI score, about 38% (n = 17) had mild disease (PASI < 10), and about 62% (n = 28) had moderate/severe disease (PASI ≥ 10). There was a significantly higher median (IQR) (25th-75th) ATG5 level in PsO 206 (97) (145-242) ng/ml than in the control 147 (98) (111-209) ng/ml (p = 0.002). An insignificant higher median level (IQR) was observed in PsO with mild disease 207(95) compared with those with moderate/severe disease 183(98.5) (p = 0.057). Dissimilarly, the median (IQR) ATG5 level was significantly lower in PsO individuals with metabolic syndrome 170(72) compared with those without 207(104) (p = 0.044). Four predictors were identified following sex and age adjustments, in the final linear regression model: PASI score, triglyceride, High-Density Lipoprotein, and presence of metabolic syndrome. There can be a connection between autophagy as measured by ATG5 and psoriasis vulgaris. ATG5 was elevated in the serum of individuals with psoriasis vulgaris. However, it decreased in patients with metabolic syndrome. No relation was found between serum ATG5 and PASI score. Psoriasis vulgaris patients may benefit from using an autophagy enhancer as a potential treatment target.

Scalp microbiome: a guide to better understanding scalp diseases and treatments.

The scalp microbiome represents an array of microorganisms important in maintaining scalp homeostasis and mediating inflammation. Scalp microbial dysregulation has been implicated in dermatologic conditions including alopecia areata (AA), dandruff/seborrheic dermatitis (D/SD), scalp psoriasis (SP) and folliculitis decalvans (FD). Understanding the impact of scalp microbial dysbiosis gives insight on disease pathophysiology and guides therapeutic decision making. Herein we review the scalp microbiome and its functional role in scalp conditions by analysis of metagenomic medical literature in alopecia, D/SD, SP, and other dermatologic disease.Increased abundance of Malassezia, Staphylococcus, and Brevibacterium was associated with SD compared to healthy controls. A higher proportion of Corynebacterium, actinobacteria, and firmicutes are present in AA patients, and lower proportions of Staphylococcus caprae are associated with worse clinical outcomes. Decreased prevalence of actinobacteria and Propionibacterium and increased firmicutes, staphylococcus, and streptococcus are associated with scalp psoriasis. Studies of central centrifugal cicatricial alopecia (CCCA) suggest scalp microbial composition contributes to CCCA's pro-inflammatory status. The most common organisms associated with FD include methicillin-resistant S. aureus and S. lugdunensis. Antifungals have been a mainstay treatment for these diseases, while other alternatives including coconut oils and shampoos with heat-killed probiotics have shown considerable potential efficacy by replenishing the scalp microbiome.

Assessing the genetic associations between plasma lipidomic profiles and psoriasis vulgaris.

Several studies have indicated a potential causal relationship between plasma standard lipids, such as high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC), and psoriasis. However, few studies have offered causal evidence of lipid species beyond these standard lipids. We conducted an analysis using a genome-wide association study (GWAS) dataset comprising 179 lipid species, including 13 types across four major categories, to identify instrumental variables (IVs) associated with plasma lipids. We utilized two GWAS datasets from the IEU and Finngen for psoriasis vulgaris as the outcome. A two-sample Mendelian randomization (MR) analysis was used to explore the causal relationship between 179 lipid species and psoriasis vulgaris in two datasets. Lipid species showing causal association in both psoriasis datasets were compared for overlap. Our study identified potential causal relationships between six lipid species and psoriasis vulgaris: phosphatidylcholine (16:1_18:2), phosphatidylcholine (18:0_18:2), phosphatidylcholine (18:1_20:4), phosphatidylethanolamine (16:0_18:2), phosphatidylinositol (18:0_20:3), and triacylglycerol (50:1). In summary, elevated plasma levels of phosphatidylcholine (16:1_18:2), phosphatidylcholine (18:0_18:2), phosphatidylethanolamine (16:0_18:2), phosphatidylinositol (18:0_20:3), and triacylglycerol (50:1) may increase the risk of psoriasis vulgaris. Conversely, plasma phosphatidylcholine (18:1_20:4) may play a protective role against psoriasis vulgaris.

Therapeutic Effect of Lecigel, Cetiol®CC, Activonol-6, Activonol-M, 1,3-Propanediol, Soline, and Fucocert® (LCAA-PSF) Treatment on Imiquimod-Induced Psoriasis-like Skin in Mice.

The individual ingredients of 1,3-Propanediol, Soline, and Fucocert® (PSF) are often used as cosmetic formulations in skin care. In addition, the mixture of Lecigel, Cetiol®CC, Activonol-6, and Activonol-M (LCAA) is often used as a cosmetic base. However, whether the combination of LCAA with PSF (LCAA-PSF) exerts a therapeutic effect on psoriasis remains unclear. In this study, mice induced with imiquimod (IMQ) were divided into three groups and administered 100 mg/day of LCAA, 100 mg/day of LCAA-PSF, or Vaseline on the dorsal skin of each mouse. Weight-matched mice treated with Vaseline alone were used as controls. Hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay(ELISA) were used to assess tissue morphology and inflammatory cytokines. RNA sequencing analysis was used to predict the mechanism underlying the action of LCAA-PSF against psoriasis, while immunohistochemical analysis validation was used to identify pertinent molecular pathways. The results demonstrated that LCAA-PSF alleviated IMQ-induced keratinocyte differentiation/ proliferation bydecreasingthe serum levels of inflammatory cytokines such as IL-6, TNF-α, IL-23, and IL-17A and the epidermisof TGFß, Ki67, CK5/6, and VEGF expression, which is associated with angiogenesis and keratinocyte differentiation/ proliferation. These findings highlight the antipsoriatic activity of LCAA-PSF in a psoriasis-like mouse model and suggest this may occurvia the inhibition of inflammatory factor secretionand the TGFß-related signal pathway.

No Evidence of Gut Microbiota Alteration in Psoriasis Patients Switching to Brodalumab after Loss of TNFα Inhibition Effect.

Biological agents used to treat severe psoriasis may alter the gut microbiota, though current knowledge is limited. This study examines whether switching from TNFα inhibitors, from which patients had reduced or lost effect, to brodalumab, an IL-17 inhibitor, affects the gut microbiota in patients with psoriasis and how these changes correlate with the clinical variables of psoriasis severity and depressive symptoms. Fecal samples from patients were collected before the treatment switch and 12 weeks after the switch and were analyzed for the microbiota composition using next-generation sequencing targeting the V3-V5 region of the 16S rRNA gene, followed by bioinformatics analysis. No significant changes in overall gut microbiota composition were observed after the treatment switch, although individual variations in the Firmicutes/Bacteroidetes ratio were noted, and no significant correlations with clinical variables were found. These findings suggest that short-term changes in gut microbiota in patients with psoriasis are limited and that dysbiosis may be influenced by the interplay of various microbial populations rather than specific taxa. This study provides a foundation for further research into the effects of biological treatments on the gut microbiota in patients with psoriasis.

Oral Exposure to Low Concentration of Fumonisin B2, but Not Fumonisin B1, Significantly Exacerbates the Pathophysiology of Imiquimod-Induced Psoriasis in Mice.

This study aimed to determine whether oral fumonisin exposure contributes to the development of psoriasis. Oral administration of fumonisin B1 (FB1, 0.1 mg/kg) or fumonisin B2 (FB2, 0.1 mg/kg) was conducted for 10 days, in addition to the induction of psoriatic symptoms through topical application of 5% imiquimod cream from day 6 to day 10 (5 days) in female BALB/c mice. The results demonstrated that oral administration of FB2 significantly exacerbated psoriatic symptoms, including skin thickness, itching behavior, transepidermal water loss, immune cell infiltration in the dermis, and proinflammatory cytokine production. However, no changes were observed following exposure to FB1. Our results confirm that oral exposure to FB2 adversely affects the pathogenesis of psoriasis by increasing skin thickness and impairing barrier function.

The Role of Gamma Delta T Lymphocytes in Physiological and Pathological Condition-Focus on Psoriasis, Atopic Dermatitis, Autoimmune Disorders, Cancer and Lymphomas.

Gamma delta (γδ) T cells are a heterogeneous population of cells that play roles in inflammation, host tissue repair, clearance of viral and bacterial pathogens, regulation of immune processes, and tumor surveillance. Recent research suggests that these are the main skin cells that produce interleukin-17 (I-17). Furthermore, γδ T cells exhibit memory-cell-like characteristics that mediate repeated episodes of psoriatic inflammation. γδ T cells are found in epithelial tissues, where many cancers develop. There, they participate in antitumor immunity as cytotoxic cells or as immune coordinators. γδ T cells also participate in host defense, immune surveillance, and immune homeostasis. The aim of this review is to present the importance of γδ T cells in physiological and pathological diseases, such as psoriasis, atopic dermatitis, autoimmune diseases, cancer, and lymphoma.

Posidonia oceanica (L.) Delile Is a Promising Marine Source Able to Alleviate Imiquimod-Induced Psoriatic Skin Inflammation.

Psoriasis is a chronic immune-mediated inflammatory cutaneous disease characterized by elevated levels of inflammatory cytokines and adipokine Lipocalin-2 (LCN-2). Recently, natural plant-based products have been studied as new antipsoriatic compounds. We investigate the ability of a leaf extract of the marine plant Posidonia oceanica (POE) to inhibit psoriatic dermatitis in C57BL/6 mice treated with Imiquimod (IMQ). One group of mice was topically treated with IMQ (IMQ mice) for 5 days, and a second group received POE orally before each topical IMQ treatment (IMQ-POE mice). Psoriasis Area Severity Index (PASI) score, thickness, and temperature of the skin area treated with IMQ were measured in both groups. Upon sacrifice, the organs were weighed, and skin biopsies and blood samples were collected. Plasma and lesional skin protein expression of IL-17, IL-23, IFN-γ, IL-2, and TNF-α and plasma LCN-2 concentration were evaluated by ELISA. PASI score, thickness, and temperature of lesional skin were reduced in IMQ-POE mice, as were histological features of psoriatic dermatitis and expression of inflammatory cytokines and LCN-2 levels. This preliminary study aims to propose P. oceanica as a promising naturopathic anti-inflammatory treatment that could be introduced in Complementary Medicine for psoriasis.

Development of Imiquimod-induced HaCaT-THP-1 co-culture for modeling of psoriasis.

Psoriasis is one of the most prevalent and chronic inflammatory disease of the skin, associated with disrupted barrier function. Currently, a widely accepted, generally usable cell culture model has not been developed yet. In the present work, we aimed to establish a co-culture model with human keratinocyte (HaCaT) and human monocyte cells (THP-1) induced by Imiquimod (IMQ), which acts on the TLR7 receptor. The role of TLR7 expressed on THP-1 cells was confirmed by immunofluorescence staining of NF-κB activation. Chloroquine (CH) was used as a receptor inhibitor, in the presence or absence of which the NF-κB pathway was activated. We determined the most effective proliferation-stimulating IMQ concentration by RTCA method and the hyperproliferative effect was investigated by wound-healing test. The effect of IMQ was compared with the effects of the anthocyanin (AC) components from the anti-inflammatory sour cherry extract that we have already studied. We found that IMQ significantly increased the migration rate however, the combined treatment resulted in a decreased migration rate compared to the IMQ treatment alone. Inflammatory cytokines were measured from the supernatant of co-culture by ELISA. During the development of the co-culture intended to model psoriasis, we confirmed the induction effect of IMQ and in the case of AC treatment, we supported the stabilizing effect of the barrier.

The mechano-chemical circuit in fibroblasts and dendritic cells drives basal cell proliferation in psoriasis.

Psoriasis is an intractable immune-mediated disorder that disrupts the skin barrier. While studies have dissected the mechanism by which immune cells directly regulate epidermal cell proliferation, the involvement of dermal fibroblasts in the progression of psoriasis remains unclear. Here, we identified that signals from dendritic cells (DCs) that migrate to the dermal-epidermal junction region enhance dermal stiffness by increasing extracellular matrix (ECM) expression, which further promotes basal epidermal cell hyperproliferation. We analyzed cell-cell interactions and observed stronger interactions between DCs and fibroblasts than between DCs and epidermal cells. Using single-cell RNA (scRNA) sequencing, spatial transcriptomics, immunostaining, and stiffness measurement, we found that DC-secreted LGALS9 can be received by CD44+ dermal fibroblasts, leading to increased ECM expression that creates a stiffer dermal environment. By employing mouse psoriasis and skin organoid models, we discovered a mechano-chemical signaling pathway that originates from DCs, extends to dermal fibroblasts, and ultimately enhances basal cell proliferation in psoriatic skin.

An Overview of Methotrexate Indications in Skin Diseases.

Methotrexate is an immunosuppressive drug with remarkable therapeutic results in the treatment of autoimmune and proliferative skin diseases. Although it has been more than half a century since it was first introduced into the therapeutic arsenal of dermatologists, there are currently no standardized therapeutic protocols regarding the prescription of methotrexate in dermatology, with the exception of psoriasis treatment. This review aims to highlight the indications and benefits of methotrexate beyond psoriasis, with a focus on a wide range of inflammatory, vesiculobullous, and proliferative dermatological pathologies.

Plasma proteins and inflammatory dermatoses: proteome-wide Mendelian randomization and colocalization analyses.

Current genome-wide association studies (GWAS) of plasma proteomes provide additional possibilities for finding new drug targets for inflammatory dermatoses. We performed proteome-wide Mendelian randomization (MR) and colocalization analyses to identify novel potential drug targets for inflammatory dermatoses. We performed MR and colocalization analysis using genetic variation as instrumental variables to determine the causal relationship between circulating plasma proteins and inflammatory dermatoses. 5 plasma proteins were found to be causally associated with dermatitis eczematosa, SLE, urticaria and psoriasis using cis-pQTLs as instrumental variables, but not found in AD and LP. 19 candidate genes with high colocalization evidence were identified. These potential drug targets still require more research and rigorous validation in future trials.

Reflectance confocal microscopy for plaque psoriasis therapeutic follow-up during an anti-interleukin-17A monoclonal antibody: an observational study.

Interleukin-17A therapeutic inhibitors are among the most effective treatment methods for moderate-to-severe plaque psoriasis (PP). Reflectance confocal microscopy is a non-invasive imaging technique already documented to be beneficial in evaluating the follow-up of PP under treatment with topical actives and phototherapy. This study aimed to assess the epidermal and dermal changes associated with psoriasis and its treatment with RCM during systemic secukinumab treatment in patients with moderate-to-severe PP. A pilot study was conducted to evaluate RCM as a non-invasive tool for monitoring secukinumab treatment in patients with PP. For patients receiving secukinumab treatment, lesional skin was selected for RCM imaging, which were recorded at all scheduled times. The RCM evaluation criteria were established based on the histopathological diagnostic criteria for psoriasis. The clinical severity of psoriasis was assessed utilizing the psoriasis area severity index. A total of 23 patients with PP were included in the study. Each patient received 300 mg of subcutaneous secukinumab as induction therapy at baseline and weeks 1-4, followed by maintenance therapy every four weeks. Microscopic confocal changes were observed during the treatment. The results identified early microscopic evidence of the anti-inflammatory activity of secukinumab, which was not detected during the clinical examination. RCM findings correlating with the PASI were used to observe the patient's response to treatment and were identified as follows: acanthosis and parakeratosis, presence of epidermal and dermal inflammatory cells, presence of non-edge dermal papillae, and vascularization in the papillary dermis. This study is the first to demonstrate the use of RCM as an effective tool for non-invasive monitoring of secukinumab therapeutic response at a cellular level in a clinical or research setting. Early detection of RCM parameters associated with secukinumab activity may facilitate the identification of an early treatment response. RCM appears to be capable of providing practical and helpful information regarding follow-up in patients with PP undergoing secukinumab treatment. RCM may also provide novel perspectives on the subclinical evaluation of PP's response to biological therapy.

Risk of neutropenia in psoriasis patients prescribed anti-IL-23 antibody in comparison with anti-IL-17 antibody or adalimumab based on real-world data from the MID-NET® in Japan.

BACKGROUND: To evaluate the risk of neutropenia during treatment with anti-IL-23 antibodies in patients with psoriasis. METHOD: We conducted an observational study with cohort design using MID-NET® in Japan. We identified patients with psoriasis who were newly prescribed anti-IL-23 antibodies, anti-IL-17-antibodies, adalimumab, or apremilast between January 1, 2009, and March 31, 2021. We estimated the adjusted hazard ratio (aHR) of anti-IL-23 antibodies compared to that of anti-IL-17 antibodies, adalimumab, or apremilast, for the risk of grade 2 (neutrophil count < 1,500/µL) or grade 3 (neutrophil count < 1,000/µL) neutropenia. RESULTS: Overall, 287 patients on anti-IL-23 antibodies, 189 patients on anti-IL-17 antibodies, 293 patients on adalimumab, and 540 patients on apremilast were included. Compared with anti-IL-17 antibodies, the aHR (95% confidence interval (CI)) of anti-IL-23 antibodies was 0.83 (0.27-2.51) for grade 2 and 0.40 (0.02-7.60) for grade 3 neutropenia; that when compared with adalimumab was 0.76 (0.28-2.06) for grade 2 but was not calculated for grade 3 as no cases were found; and that compared with apremilast was 3.88 (0.62-24.48) for grade 2 and 0.43 (0.02-11.63) for grade 3 neutropenia. CONCLUSION: No clear increase in the risk of neutropenia with anti-IL-23 antibodies was observed.

Resistin Gene Promoter -420C>G (rs1862513) and +299 G>A (rs3745367) Polymorphisms in Psoriasis.

BACKGROUND: The pro-inflammatory adipokine resistin is known to be related to obesity, insulin resistance, and inflammation. Resistin's significance in the etiology of inflammatory illnesses, such as psoriasis, is explored herein. We examined the link between resistin gene polymorphisms (-420 C>G and +299 G>A) and psoriasis in the Turkish population. METHODS: In this study, we examined 107 patients with psoriasis and 103 healthy controls. Resistin -420 C>G (rs1862513) and +299 G>A (rs3745367) gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: In patients with psoriasis, the frequency of the resistin -420 CG genotype was meaningfully lower than in the controls. In comparison with the controls, the resistin +299 GA genotype and A allele frequencies were significantly higher. The Resistin -420 CG genotype significantly reduced the risk of psoriasis incidence, while the resistin +299 GA genotype and A allele were found to be associated with a higher risk of psoriasis. CONCLUSIONS: In the Turkish community, resistin gene polymorphisms at -420 C>G and +299 G>A may exert an important influence on psoriasis etiology and susceptibility.