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.

Characterization of psoriasis patients in special body areas: real-world evidence from the Chinese Psoriasis Standardized Diagnosis and Treatment Center.

BACKGROUND: While extensive research has provided a wealth of information on psoriasis in general, there remains a critical gap in understanding the unique characteristics of psoriasis in special body areas, such as the scalp, nails, palms, and genitals. OBJECTIVE: To investigate the characterization and treatment of psoriasis patients in special body areas. METHODS: The study was a retrospective analysis of patients with psoriasis enrolled in the Psoriasis Standardized Diagnosis and Treatment Center Project between January 2020 and September 2021. RESULTS: The study encompassed 346 patients, 81% of them had psoriasis in at least two special body areas, with the nails as the most common area. Patients with genital psoriasis reported higher Dermatology Life Quality Index (DLQI) scores. A higher propensity for scalp and palmoplantar psoriasis was noted in patients with genital psoriasis. The proportion of patients treated with biologics rose, as the number of specific areas involved increased. CONCLUSIONS: Patients with genital psoriasis are more likely to have scalp and palmoplantar psoriasis. This study highlights the significant escalation in the proportion of biologics when the involvement of special body areas was ≥2.

Role of Claudin- 3 as a biomarker of gut-skin axis integrity in patients with psoriasis.

Increased intestinal permeability and gut dysbiosis are important factors in the pathophysiology of psoriasis and its associated conditions. Claudin-3 is a protein that is found in tight junctions and may be used to assess the integrity of the gut barrier. The aim of this study was to investigate serum concentration of Claudin- 3 (CLDN3) in patients with psoriasis. Exploring its possible relations with patients' demographic, clinical and laboratory findings was another objective. Fifty psoriatic patients and thirty-five age- and sex-matched healthy volunteers served as the study's control group in this case-control, hospital-based research. The amount of serum CLDN3 was determined by means of an enzyme-linked immunosorbent test (ELISA). Concentration of serum CLDN3 was found to be significantly higher in patients with psoriasis. (p = 0.002). There was no statistically significant correlation between CLDN3 and patient's clinical & laboratory variables. We demonstrated that gut permeability is dysfunctional in patients with psoriasis as indicated by reduction of serum CLDN3. Further investigations are needed to determine whether modulation of gut barrier may represent a new therapeutic approach for psoriasis.

Assessing the relationship between psoriasis and thyroid dysfunction through two sample MR analysis.

BACKGROUND: The association between psoriasis and hyperthyroidism/hypothyroidism remains inconclusive, with conflicting findings in prior studies. OBJECTIVES: This study employs Mendelian randomization methods to assess the potential relationship. METHODS: Given the inability to accurately observe the link between psoriasis and thyroid dysfunction, we prioritized utilizing known genetic variants to investigate the potential impacts of the disease.We analyzed data from genome-wide association studies (GWASs), FinnGen, and UK Biobank to extract information on psoriasis, hyperthyroidism, and hypothyroidism. Three MR approaches (MR Egger, weighted median, and inverse variance weighted) were used to scrutinize the causal link. RESULTS: Our analysis revealed no correlation between psoriasis and hyperthyroidism/hypothyroidism. However,  vulgar psoriasis and guttate psoriasis were associated with hypothyroidism/myxedema (IVW odds ratio (OR) = 1.00, 95% confidence interval (CI) = 1.00-1.00, P = 2.53E-03), and Graves' disease (IVW OR = 0.86, 95% CI = 0.72-1.01, P = 4.75E-02).In a subsequent analysis, we observed that hypothyroidism with mucinous edema showed no correlation with Graves' disease in the opposite(P = 9.33E-01). CONCLUSION: This MR analysis suggests no association between psoriasis and thyroid dysfunction, but highlights associations of vulgar/guttate psoriasis with hypothyroidism/myxedema and Graves' disease. In clinical practice, diagnosing guttate psoriasis requires vigilance for associated risks from hypothyroidism and Graves' disease. For patients with both vulgar psoriasis and hypothyroidism, careful monitoring for mucinous edema is crucial, as it may signal a hypothyroid crisis.

Safety and effectiveness of apremilast in Japanese patients with psoriatic disease: Results of a post-marketing surveillance study.

The safety and efficacy of apremilast in psoriatic disease has been demonstrated in clinical trials, including in Japanese patients. This post-marketing surveillance study was conducted after approval of apremalast in Japan in 2016 to evaluate the safety and effectiveness of the drug in Japanese patients with plaque psoriasis (PsO) and psoriatic arthritis (PsA) in routine clinical practice. Patients (enrolled between September 1, 2017, and August 31, 2019), were observed for 12 months after apremilast treatment initiation or until discontinuation or withdrawal. Safety was assessed by evaluating adverse reactions (ARs) and serious ARs. Effectiveness measures in PsO included the proportion of patients who achieved global improvement and Physician's Global Assessment (PGA) scores of 0/1 and the change from baseline in the Dermatology Life Quality Index (DLQI) after 6 and 12 months treatment. The safety analysis set included 1063 patients (PsO, n = 992; PsA, n = 127). ARs and serious ARs were reported in 29.4% and 0.7% of patients, respectively; most occurred <1 month after apremilast initiation. There were no reports of fatal ARs, serious infections, hypersensitivity, or vasculitis. No new safety signals were identified. Among the key survey items, gastrointestinal disorders were the most common ARs (21.3%). In patients with PsO, after 6 and 12 months of treatment, effectiveness rates of achieving highly effective or effective global improvement of were 90.9% and 93.8%; PGA 0/1 was achieved by 42.7% and 58.1% of patients; mean decrease from baseline in total DLQI score was 4.2 (p < 0.0001) and 5.7 (p < 0.0001), respectively. Effectiveness was evaluated in a small number of patients with PsA for some measures; after 6 and 12 months of treatment, improvements were observed in global improvement effectiveness rates, Disease Activity Score in 28 Joints score, Visual Analog Scale score, and DLQI score. We conclude that orally administered apremilast was well tolerated and effective in Japanese patients with PsO and/or PsA enrolled in this post-marketing surveillance study.

Associations of novel complete blood count-derived inflammatory markers with psoriasis: a systematic review and meta-analysis.

Psoriasis is an immune-mediated disorder which primarily affects skin and has systemic inflammatory involvement. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and monocyte-to-lymphocyte ratio (MLR) are novel complete blood count (CBC)-derived markers which can reflect systemic inflammation. This study aimed to systematically investigate the associations of NLR, PLR, SII, and MLR with psoriasis. This study was performed in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. A comprehensive search of Pubmed, Embase, Scopus, and Google Scholar was conducted for relevant studies. Observational studies evaluating the correlations of NLR, PLR, SII, or MLR with psoriasis were included. The primary outcomes were the associations of these inflammatory markers with the presence and severity of psoriasis. The random-effect model was applied for meta-analysis. 36 studies comprising 4794 psoriasis patients and 55,121 individuals in total were included in the meta-analysis. All inflammatory markers were significantly increased in psoriasis groups compared to healthy controls (NLR: MD = 0.59, 95% CI: 0.47-0.7; PLR: MD = 15.53, 95% CI: 8.48-22.58; SII: MD = 111.58, 95% CI: 61.49-161.68; MLR: MD = 0.034, 95% CI: 0.021-0.048; all p < 0.001). Between-group mean differences in NLR and PLR were positively correlated with the mean scores of Psoriasis Area Severity Index (NLR: p = 0.041; PLR: p = 0.021). NLR, PLR, SII, and MLR are associated with the presence of psoriasis. NLR and PLR serve as significant indicators of psoriasis severity. These novel CBC-derived markers constitute potential targets in the screening and monitoring of psoriasis.

Evaluation of the inflammatory parameters as potential biomarkers of systemic inflammation extent and the disease severity in psoriasis patients.

The disease severity of psoriasis is mainly assessed subjectively via  psoriasis area and severity index (PASI) and body surface area (BSA), while an optimal measure of cutaneous response, may overlook systemic inflammation in psoriasis patients. The neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), monocyte to high density lipoprotein ratio (MHR), and systemic immune-inflammation index (SII) exhibit notable associations with the inflammation severity in multiple diseases. The aim of this retrospective study was to explore the associations between inflammatory parameters and the skin lesions' severity of psoriasis. After analysis, we found that patients with psoriasis had higher NLR, MLR, PLR, MHR, and SII levels compared to the control group. At baseline, the parameters of NLR (r = 0.124, P = 0.003), MLR (r = 0.153, P < 0.001), MHR (r = 0.217, P < 0.001) and SII (r = 0.141, P = 0.001) had a positive correlation with PASI in psoriasis patients. At the same time, we analyzed the patients who received different systemic therapy. We observed a significant decrease in NLR, PLR, MLR, and SII in psoriasis patients after treatment. Notably, TNF-α inhibitors and IL-17A inhibitors subgroups showed a more significant reduction than IL-23/IL-12/23 inhibitors and MTX medication. Additionally, we found the change of NLR (r = 0.194, P < 0.001), PLR (r = 0.104, P = 0.014), MLR (r = 0.191, P < 0.001), MHR (r = 0.106, P = 0.012), and SII (r = 0.228, P < 0.001) had a positive correlation with the change of PASI in psoriasis patients. In conclusion, this study suggests that NLR, MLR, and SII may serve as useful biomarkers for assessing systemic inflammation extent and disease severity in psoriasis patients.

Proteomic identification of exosomes derived from psoriasis cells using data-independent acquisition mass spectrometry.

Psoriasis is renowned for its chronic nature and complex pathophysiology, with exosomes playing a crucial regulatory role within it. However, the proteomic composition of exosomes extracted from psoriasis cells remains largely unexplored. This study aimed to analyze the proteomic makeup of exosomes derived from psoriasis-model keratinocytes and compare it with that of normal controls, with the goal of identifying specific proteins that could aid in understanding the disease's pathology and potentially serve as biomarkers or therapeutic targets. The normal cultured keratinocyte line HaCaT served as the control group, while a concentration of 10 ng/mL of TNF-α was utilized to stimulate HaCaT cells and induce the formation of psoriasis model cells for the test group. Exosomes were extracted and prepared from the culture supernatant using the magnetic bead method, and their identity was confirmed through transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. Data-independent acquisition (DIA) mass spectrometry was employed to detect the protein composition of exosomes, followed by GO, KEGG, Reactome, and PPI analyses. The analysis revealed a total of 2796 proteins within the exosomes, with 131 showing significant differential expression between the test and control groups. Notably, this study identified the proteins ADO, CBX1, and MIF within the exosomes derived from psoriasis model cells for the first time, highlighting their potential roles in angiogenesis, epigenetic regulation, and inflammatory responses in psoriasis. Several differentially expressed proteins identified in the KEGG enrichment analysis were implicated in immune infiltration pathways, keratinocyte-regulating pathways, angiogenesis pathways, and inflammation pathways. The identification of unique proteins within exosomes derived from psoriasis-model cells offers novel insights into the molecular mechanisms underlying psoriasis. These findings pave the way for further research into the biological functions of these exosomal proteins and their potential utility in diagnosing and treating psoriasis.

Differences between psoriatic arthritis and psoriasis in multi-omics.

We aim to systemically review the genomics, transcriptomics, epigenetics, proteomics, metabonomics and microbiota of psoriatic arthritis and psoriasis, illustrating the differences of these two diseases, broadening our understanding of the pathogenesis of them and providing important clues for valuable biomarkers of earlier diagnosis and treatments. To our knowledge, this is the first study that combine all omics studies from genomics to microbiota and may serve as a reference for future studies to identify the key underlying pathways in psoriatic arthritis.