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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 β2-microglobulin (β2M) in psoriasis severity and comorbidities., Objectives: To investigate the correlation between blood β2M 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 β2M and ESR were observed in the group that patients' PASI ≥10 than in the group that PASI <10. Blood β2M 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 β2M 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 β2M levels and severer inflammatory state. In the systemic inflammation indexes, the level of blood β2M affected the risk of hypertension and diabetes, and hsCRP affected the risk of arthritis in patients with psoriasis.

Background: There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients., Methods: In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12., Results: At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician's Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs . 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs . 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab., Conclusion: Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis., Trial Registration: ClinicalTrials.gov , NCT05108766., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: Reports on the prevalence of psoriatic arthritis (PsA) among Chinese patients with psoriasis are very limited. This study, conducted by rheumatologists, estimated the prevalence of PsA in a large number of Chinese patients with psoriasis., Methods: Consecutive patients with a confirmed diagnosis of psoriasis attending nine dermatology clinics in five hospitals were recruited. All psoriasis patients were asked to complete a questionnaire comprising 16 questions to identify possible cases of PsA. All patients with one or more positive answers to the questionnaire were evaluated by two experienced rheumatologists., Results: A total of 2434 psoriasis patients, including 1561 males and 873 females, were enrolled. Both the questionnaire and rheumatologists' examinations were completed in the dermatology clinics. The results identified 252 patients with PsA, comprising 168 males and 84 females. The overall prevalence of PsA among psoriasis patients was 10.4% (95% confidence interval [95% CI], 9.1%-11.7%). By sex, the prevalence was 10.8% (95% CI, 9.2%-12.5%) for males and 9.6% (95% CI, 7.7%-11.9%) for females and there was no significant sex difference in the prevalence of PsA (P = 0.38). Of the 252 PsA patients, 125 (49.6%, 95% CI, 41.3%-59.1%) were newly diagnosed by rheumatologists. Consequently, the prevalence of undiagnosed PsA among psoriasis patients was 5.2% (95% CI, 4.4%-6.2%)., Conclusion: The prevalence of PsA in the Chinese population with psoriasis is about 10.4%, which is almost double that of previous reports in the Chinese population, but lower than that in Caucasians., (Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Vγ9Vδ2 T cells play an important role in the development and progression of psoriasis vulgaris (PV), but how they promote skin inflammation and the molecular mechanisms underlying Vγ9Vδ2 T cell dysfunction are poorly understood. Here, we show that circulating Vγ9Vδ2 T cells are decreased and exhibit enhanced proliferation and increased production of IFN-γ and TNF-α in PV patients. Monocytes from PV patients express higher levels of the phosphoantigen sensor butyrophilin 3A1 (BTN3A1) than monocytes from healthy controls. Blockade of BTN3A1 suppresses Vγ9Vδ2 T cell activation and abolishes the difference in Vγ9Vδ2 T cell activation between PV patients and healthy controls. The CD14 + cells in PV skin lesions highly express BTN3A1 and juxtapose to Vδ2 T cells. In addition, IFN-γ induces the up-regulation of BTN3A1 on monocytes. Collectively, our results demonstrate a crucial role of BTN3A1 on monocytes in regulating Vγ9Vδ2 T cell activation and highlight BTN3A1 as a potential therapeutic target for psoriasis.

Background: Methotrexate (MTX) has a protective effect against cardiovascular diseases (CVD), but the mechanism is unclear., Objective: To investigate the effect of MTX on lipid profiles and the difference between psoriasis without arthritis (PsO) and psoriatic arthritis (PsA)., Methods: In this prospective study, we recruited 288 psoriatic patients (136 PsA and 152 PsO) who completed 12 weeks of MTX treatment. Total cholesterol (TC), triglycerides (TG), lipoprotein A [LP(a)], high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), and ApoB were measured., Results: Compared with sex- and age-matched healthy controls, psoriatic patients had significantly (p < 0.0001) higher levels of proatherogenic lipids and lower levels of anti-atherogenic lipids. PsA patients had a higher ApoB/ApoA1 ratio than PsO patients (p < 0.05). Stepwise regression analysis found a positive correlation between the inflammatory marker hCRP and the Psoriasis Area Severity Index (PASI), ApoB/ApoA1 ratio, BMI, and smoking. ApoB was positively associated with concomitant arthritis, diabetes, and hypertension. MTX decreased the levels of pro-atherogenic and anti-atherogenic lipids. However, a significant reduction of the ApoB/ApoA1 ratio by MTX was only observed in male patients., Conclusion: PsA patients had a significantly higher percentage of concomitant disease than PsO. The decrease of MTX on CVD might be related with sex., Trial Registration: ChiCTR2000036192., (© 2022. The Author(s).)

Background: Biomarkers for distinguishing psoriatic arthritis (PsA) from psoriasis without arthritis (PsO) are still lacking., Methods: We applied isobaric tags for relative and absolute quantification (iTRAQ) and LC-MS/MS to analyze the proteome profile of peripheral blood mononuclear cells (PBMCs) collected from patients with PsO, patients with PsA, and healthy controls. Bioinformatics analysis and western blotting were performed to identify and validate differentially expressed proteins., Results: We identified 389, 199, 291, and 60 significantly differentially expressed proteins (adj.p < 0.05) in the comparison of all psoriatic patients versus healthy controls, PsO group versus healthy controls, PsA group versus healthy controls, and PsA group versus PsO group, respectively. Among these proteins, 14 proteins may represent promising biomarkers for PsA: SIRT2, NAA50, ARF6, ADPRHL2, SF3B6, SH3KBP1, UBA3, SCP2, RPS5, NUDT5, NCBP1, SYNE1, NDUFB7, HTATSF1. Furthermore, western blotting confirmed that SIRT2 expression was significantly higher in PBMCs from PsA patients than PsO and healthy controls, and was negatively correlated with the phosphorylation of p38 mitogen-activated protein kinase (p-p38MAPK; p = 0.006, r = - 0.582)., Conclusions: This pilot study provided a broad characterization of the proteome of PBMCs in PsA as compared to PsO and healthy controls, which may help to provide prospective strategies for PsA diagnosis., (© 2021. The Author(s).)

Background: The anti-inflammatory effect of glycyrrhizin has been widely recognized, while the specific mechanism of glycyrrhizin in psoriasis remains poorly understood., Results: In the imiquimod-induced mouse model of psoriasis (IMD), we found that glycyrrhizin can substantially improve the adverse symptoms in mice. The hematoxylin-eosin staining results showed that glycyrrhizin can also improve the pathological state of skin cells in IMD mice. Using enzyme-linked immunosorbent assay (ELISA), we found that glycyrrhizin substantially inhibited the expression of IL-17A and IFN-γ in the serum of IMD mice. In order to simulate the effect of IL-17A on keratinocytes in psoriasis, we treated HaCaT cells with 100 ng/mL IL-17A (IL-17A-HaCaT cells) for 48 h. Then, using cell-counting kit-8 (CCK-8) and ELISA assays, we found that glycyrrhizin inhibited the proliferation of IL-17A-HaCaT cells and reversed the promotion of IL-6, CCL20, and TNF-α induced by IL-17A. Further, western blotting (WB) results indicated that glycyrrhizin promoted the expression of SIRT1 and inhibited the expression of STAT3 and phosphorylated STAT3 (p-STAT3). By treating IL-17A-HaCaT cells with EX-527 (a potent and selective inhibitor of SIRT1), combined with CCK-8 and WB experiments, we initially found that EX-527 inhibited the proliferation of IL-17A-HaCaT cells and promoted the expression of STAT3, p-STAT3, and acetylated STAT3 (a-STAT3). However, when glycyrrhizin was added at the same time, the proliferation of IL-17A-HaCaT cells increased, and the expression of STAT3, p-STAT3, and a-STAT3 reduced. We then knocked down the expression of SIRT1 via small interfering RNA in IL-17A-HaCaT cells, and the results were consistent with those of EX-527., Conclusions: Together, these results indicated that glycyrrhizin improved psoriasis by inhibiting the expression of IL-17A and IFN-γ in vivo and suppressed the proliferation of IL-17A-HaCaT cells and the expression of STAT3, p-STAT3, and a-STAT3 by upregulating SIRT1 in vitro.

Psoriasis-2 (PSORS2) is caused by the heterozygous mutation of the caspase recruitment domain 14 ( CARD14 ) gene on chromosome 17q25. To evaluate the contribution of CARD14 variants in psoriasis of the Chinese Han population, we performed deep sequencing of the CARD14 gene in 372 Chinese Han patients with psoriasis. The exonic nucleotide variants were confirmed by Sanger sequencing in the affected individuals and 1114 controls. In 27 patients with psoriasis, we identified 15 variations, including three novel variants: c.381C[G (p.Cys127Trp), c.712A[G (p.Met238Val) and c.2260&#95;2261delinsGG (p.Gln754Gly). These findings could enrich and update the Human Gene Mutation Database of CARD14 variants for psoriasis.

Background: Annexin A6 (AnxA6) is a lipid-binding protein that regulates cholesterol homeostasis and secretory pathways. However, the correlation of AnxA6 polymorphism with lipometabolism has never been studied in psoriasis. Objectives: To investigate the impact of AnxA6 polymorphism on lipid profiles and the expression of AnxA6 protein in both peripheral blood mononuclear cells (PBMCs) and lipometabolism in psoriasis. Methods: A total of 265 psoriatic patients received methotrexate (MTX) treatment for 12 weeks, after which their lipid profiles were determined by measuring total cholesterol (TC), triglycerides (TGs), lipoprotein (a) [LP(a)], high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL), apolipoprotein (a)1 (ApoA1), and apolipoprotein B (ApoB). In addition, AnxA6 (rs11960458) was genotyped in 262 patients and the expression of AnxA6 in PBMCs was measured by Western blotting at baseline and week 8 post-MTX treatment. Results: The CC genotype carriers of rs11960458 had a lower expression of AnxA6 and lower levels of the pro-atherogenic lipids TC, LDL, and ApoB compared to TC genotype carriers. MTX significantly downregulated the levels of the anti-atherogenic lipids HDL-C and ApoA1 and the level of AnxA6 in TC genotype carriers, as well as the level of TGs in CC genotype carriers. Conclusions: The polymorphism of AnxA6, rs11960458, was statistically associated with the levels of pro-atherogenic lipids and with the downregulation of MTX on the levels of anti-atherogenic lipids and TGs in psoriasis. [ABSTRACT FROM AUTHOR]

Background: The co-inhibitory molecule B7-H4 is located in the genomic regions associated with type 1 diabetes (T1D) susceptibility. However, the correlation of B7-H4 with glycometabolism and dyslipidemia has never been studied. Objective: To explore the influence of B7-H4 polymorphism on the prevalence of diabetes mellitus (DM) and dyslipidemia in psoriasis. Methods: In this single-center cross-sectional study, we recruited 265 psoriatic patients receiving methotrexate (MTX) treatment. Thirteen single-nucleotide polymorphisms (SNPs) in B7-H4 were genotyped. Serum levels of total cholesterol (TC), triglycerides (TG), lipoprotein (a) (LP(a)), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB) were measured at baseline and week 12. Results: The GG genotype carriers of rs12025144 in B7-H4 had a higher prevalence of DM (57.14% vs. 17.71% vs. 18.67%, p = 0.0018), and had a poorer response to MTX in diabetic patients (p < 0.05), compared with AA or AG genotype carriers. The AG genotype of rs2066398 was associated with higher levels of pro-atherogenic lipids. MTX significantly downregulated the level of anti-atherogenic lipid ApoA1 in AA genotype carriers of rs2066398. Conclusions: The genotypes rs12025144 and rs2066398 in B7-H4 were correlated with a higher prevalence of DM and dyslipidemia in psoriasis, respectively. [ABSTRACT FROM AUTHOR]

Background: Hyperhomocysteinemia has been reported in psoriasis. We investigated the effect of methylenetetrahydrofolate reductase (MTHFR), polymorphism and folic acid supplementation on serum homocysteine levels in psoriasis. Methods: Serum homocysteine levels were detected at baseline and at week 12 in 201 patients who were genotyped with MTHFR rs1801133 without and 93 psoriatic patients with folate supplement. Results: TT genotype carriers of MTHFR rs1801133 had significantly higher serum homocysteine levels at baseline and at week 12, a better PASI 75 response rate at week 8, and a higher PASI 90 response rate at week 12 than the CT and CC genotype carriers. Multiple regression analysis demonstrated that serum homocysteine concentration at baseline was significantly associated with sex, weight, PASI score at baseline, and the rs1801133 genotype. The significant upregulation of serum homocysteine levels after treatment with methotrexate (MTX) was only observed in male CT and CC genotype carriers and female CC genotype carriers. In contrast, folic acid supplementation significantly decreased serum homocysteine levels after MTX treatment but only in male psoriatic patients. Conclusions: The effect of MTX on serum homocysteine levels was associated with the polymorphism of MTHFR rs1801133 and sex. Folic acid supplementation only decreased serum homocysteine levels in male psoriatic patients. [ABSTRACT FROM AUTHOR]