Expert Consensus on the Application of Stem Cells in Psoriasis Research and Clinical Trials.

Psoriasis is an immune-mediated, chronic, relapsing, inflammatory, systemic disease induced by individual-environmental interactions, and is often lifelong because of the difficulty of treatment. In recent years, a variety of targeted therapies, including biologics, have improved the lesions and quality of life of most psoriasis patients, but they still do not address the problem of relapse and may be associated with decreased efficacy or adverse events such as infections over time. Therefore, there is an urgent need for breakthroughs in psoriasis treatment and in relapse-delaying and non-pharmacologic strategies, and stem cell therapy for psoriasis has emerged. In recent years, research on stem cell therapy for psoriasis has received a lot of attention, however, there is no reference standard as well as consensus in this field of research. Therefore, according to the latest consensus and guidelines, combined with relevant literature reports, clinical practice experience and the results of discussions with experts, this consensus specifies the types of stem cells commonly used in the treatment of psoriasis, the methods, dosages, and routes of stem cell therapy for psoriasis, as well as the clinical evaluations (efficacy and safety) of stem cell therapy for psoriasis. In addition, this consensus also provides normative standards for the processes of collection, preparation, preservation and quality control of stem cells and their related products, as well as recommendations for the management of stem cells during infusion for the treatment of psoriasis. This consensus provides the latest specific reference standards and practice guidelines for the field of stem cell therapy for psoriasis.

Adsorption of Cu Nanoparticles on Polystyrene-Based Microspheres.

Nanoparticle composite microspheres are a versatile material with unique features and wide-ranging applications, including catalysis, biological medicine, and electronic devices. The adsorption behavior of nanoparticles on the surface of microspheres plays a crucial role in determining the further application potentials. The understanding of nanoparticle adsorption behavior on microsphere surfaces is essential for guiding future applications in nanoparticle composite microspheres. In this work, the adsorption behavior of unstable copper nanoparticles (Cu NPs) on polystyrene-based (PS-based) microspheres was investigated. The influence of PS-based microspheres' surface properties and the oxidation degree of Cu NPs were determined. The adsorption mechanism of Cu NPs on PS-based microspheres was analyzed. Furthermore, the amounts and rates of adsorption were examined. It was found that the Cu NPs can be rapidly and firmly adsorbed on the surface of carboxyl-modified polystyrene microspheres. Additionally, precise control over the distribution of Cu NPs on the surface of PS-based microspheres can be achieved by manipulating the solvent's polarity.

Clinical characteristics and outcomes of psoriasis patients with COVID-19: A retrospective, multicenter cohort study in China.

BACKGROUND: Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection. METHODS: A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with COVID-19-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2. RESULTS: Among the infected group, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685-11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068-2.343), traditional systemic (adjusted OR = 1.887, 95% CI = 1.263-2.818), and nonsystemic treatment (adjusted OR = 1.602, 95% CI = 1.117-2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680-1.274, compared to no treatment), according to multivariable logistic regression analysis. CONCLUSIONS: A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension. TRIAL REGISTRATION: ClinicalTrials.gov (No. NCT05961605).

Positive association between insulin resistance and fatty liver disease in psoriasis: evidence from a cross-sectional study.

Background: Fatty liver disease (FLD) is a common comorbidity of psoriasis and is often referred to as non-alcoholic fatty liver disease (NAFLD). However, the role of inflammation or insulin resistance (IR) in FLD is inconclusive. The study aims to explore whether FLD in psoriasis patients is more related to insulin resistance or systemic inflammation level. Methods: Data for this study were collected from the Shanghai Psoriasis Effectiveness Evaluation Cohort, a prospective cohort that examines psoriasis characteristics in the Chinese population. IR was assessed using the triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) indicators. Systemic non-specific inflammation was assessed using the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), and systemic immune inflammation index (SII). Results: The analysis included a total of 647 patients. Subsequent logistic regression analysis revealed that NLR, dNLR, and SII were not significantly associated with FLD in psoriasis patients, while TyG and TyG-BMI showed significant associations with FLD. Subgroup analysis indicated that in the majority of subgroups, TyG and TyG-BMI were significantly associated with FLD, particularly TyG-BMI. Excluding individuals with methotrexate and acitretin resulted in consistent findings with the main analysis. Further analysis revealed a significantly higher diagnosis rate of metabolic-associated fatty liver disease (MAFLD) compared to NAFLD. Conclusions: Metabolic factors play a crucial role in FLD in patients with psoriasis, and TyG and TyG-BMI are potential predictors of FLD. Therefore, MAFLD can be recommend as a term to describe FLD in psoriasis patients. Trial registration: https://www.chictr.org.cn/showproj.html?proj=58256, identifier ChiCTR2000036186. A multi-center clinical study of systemic treatment strategies for psoriasis in Chinese population. Registered 31 August 2020.

Disease Burden and Coping Strategies of Spouses of Patients with Psoriasis: A Qualitative Study.

Background: Psoriasis is a chronic autoimmune inflammatory skin condition characterized by erythema, papules, and scales. It imposes a heavy psychological and social strain on both patients and their families. Surprisingly, there's limited research delving into the disease burden and coping strategies of spouses contending with psoriasis. Objective: The objective is to explore the disease burden faced and coping strategies utilized by spouses of individuals living with psoriasis. This exploration aims to offer insights crucial for devising mental health support and intervention strategies. Methods: The research methodology employed in this study was phenomenological, a qualitative approach. A total of fifteen spouses of patients with psoriasis were selected using an objective sampling method for in-depth, semi-structured interviews. Thematic analysis was then applied to the recorded interview data to derive meaningful themes. Results: This study has identified and analyzed three core themes concerning the disease burden and coping strategies of spouses of patients with psoriasis: Overwhelming disease burden; Lack of support system; Coping strategies (Problem - centered coping strategies: Proactive acquisition of disease knowledge; Active confrontation of illness - related issues; Behavioral habit alteration; and Emotional - centered coping strategies: Active acceptance and normalization; Passive acceptance and internalized stigma; Avoidance of disease - related problems). Conclusion: This study adds valuable insights into comprehending the disease burden encountered by spouses of patients with psoriasis and sheds light on the coping strategies they employ. Healthcare providers should proactively recognize and address the burden experienced by spouses early on. Establishing a robust support network is crucial, and promoting adaptive coping strategies can significantly aid spouses in effectively navigating and managing the complexities associated with psoriasis.

Insulin Resistance Impairs Biological Agents Response in Moderate-to-Severe Plaque Psoriasis: Insights from a Prospective Cohort Study in China.

BACKGROUND: Psoriasis and insulin resistance (IR) are closely related, but it remains unclear whether IR affects the treatment of patients with psoriasis. OBJECTIVE: The objective of this study was to investigate whether IR impairs the treatment response to biologic agents in patients with moderate-to-severe plaque psoriasis. METHODS: This project was based on a prospective cohort study design. Data for this study were collected from the Shanghai Psoriasis Effectiveness Evaluation CoHort (SPEECH), which is a prospective cohort exploring treatment strategies for psoriasis in China. IR was assessed using the triglyceride glucose-body mass index (TyG-BMI). Psoriasis severity was assessed using the Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA). Multiple logistic regression was used to explore the differences between patients with high and low levels of IR. Subgroup and sensitivity analyses were performed to examine the robustness of the study results. RESULTS: A total of 290 patients were included in the analysis. Based on the median TyG-BMI, the patients were divided into two groups: High and Low. The High group exhibited a higher prevalence of diabetes, higher BMI, fasting blood glucose, and triglyceride compared with the Low group. Further analysis of the treatment efficacy revealed that the High group had lower response rates for PASI 75, PASI 90, and PGA 0/1 after 12 weeks of treatment. In the Low group, 81.94% of patients achieved PASI 75, 58.33% achieved PASI 90, and 75.69% achieved PGA 0/1. However, the proportion of responses at each endpoint was significantly lower in the High group. The impairment in response to PGA 0/1 was more significant in the High group, indicated by lower odd ratios. Subsequent subgroup analysis and sensitivity analysis produced consistent results. CONCLUSION: IR is associated with lower effectiveness of biologics in patients with psoriasis. CLINICAL TRIAL REGISTRATION: [www.chictr.org.cn], identifier [ChiCTR2000036186].

The Safety of Ixekizumab in Chinese Adults with Moderate-to-Severe Plaque Psoriasis: Analyses from a Prospective, Single-Arm, Multicenter, 12-Week Observational Study.

INTRODUCTION: Ixekizumab, a monoclonal antibody against interleukin-17A, is efficacious and well tolerated for the treatment of moderate-to-severe plaque psoriasis. However, there are limited data on the real-world safety of ixekizumab in Chinese patient populations. We performed an observational study of ixekizumab for the treatment of moderate-to-severe plaque psoriasis in routine clinical practice in China. Here we present a further safety analysis of this study. METHODS: In this prospective, observational, single-arm, multicenter, post-marketing safety study, adults (≥18 years) with moderate-to-severe plaque psoriasis receiving ixekizumab were enroled at dermatology departments in hospitals across China and prospectively followed for 12 weeks or until their last dose of ixekizumab. In this analysis, we evaluated adverse events (AEs) of special interest (AESIs) identified using MedDRA® search strategies. We also analyzed AEs and AESIs occurring in greater than ten patients in subgroups by age (< 65/≥ 65 years), sex, body weight (< 60/60 kg to < 80/≥ 80 kg), renal impairment, hepatic impairment, history of tuberculosis, history of HBV infection, recent or active infection, history of allergic reaction/hypersensitivity, and number (0-1/2-4/5-7) of ixekizumab 80 mg injections after baseline until day 105. RESULTS: This analysis included 663/666 patients enrolled in the primary study. At least one AESI was reported in 224 (33.8%) patients and considered related to ixekizumab in 181 (27.3%); the most common were injection site reactions (n = 131, 19.8%), infections (n = 80, 12.1%), and allergic reactions/hypersensitivity events (n = 59, 8.9%). The proportion of patients with ≥ 1 AE was higher for females versus males (99/186, 53.2% versus 184/477, 38.6%, p = 0.0006). The proportion of patients with ≥ 1 AE increased with the number of ixekizumab injections after baseline [61/188 (32.4%) for zero to one injection, 151/338 (44.7%) for two to four injections, and 61/106 (57.5%) for five to seven injections; p = 0.0001]. CONCLUSIONS: In this real-world study, ixekizumab was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis, with no difference in safety across most patient subgroups.

Effectiveness of Ixekizumab in Chinese Patients with Moderate-Severe Plaque Psoriasis with Special Area Involvement: Subanalysis of a Prospective, Multicenter, Observational Real-World Study.

INTRODUCTION: Ixekizumab, a monoclonal antibody against interleukin-17A, demonstrated effectiveness in the treatment of psoriasis in a Chinese real-world study that was consistent with previous randomized controlled trials. Here, we report further analyses from this study to explore the effectiveness of ixekizumab for treating patients with psoriasis and the involvement of special body areas (scalp, nail, joint, palmoplantar, or genital areas). METHODS: A multicenter, prospective, observational, single-arm, post-marketing surveillance study was conducted in patients aged ≥ 18 years with moderate-to-severe plaque psoriasis and prescribed with ixekizumab in 26 Chinese hospitals. Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores were compared between patients with versus without psoriasis in special body areas in the overall study population and across subgroups by body area. RESULTS: In total, 612 patients were included. At baseline, most patients (93.6%) had psoriasis involvement in at least one special body area. Overall, patients with psoriasis in special body areas reported a worse quality of life (QoL) than those without. Patients with versus without psoriasis in special body areas achieved a comparable mean reduction from baseline in PASI score (10.9 vs. 9.2 at week 2, and 16.9 vs. 14.7 at week 12, respectively) and DLQI score (6.0 vs. 4.4 at week 2, and 9.9 vs. 7.5 at week 12, respectively); a similar proportion of patients also achieved PASI 50 at week 2, and PASI 75 and PASI 90 at week 12, and a DLQI (0/1) at weeks 2 and 12. Several significantly different results were reported between subgroups, the majority of which favored patients with special body area involvement. CONCLUSION: Most patients had psoriasis involvement in a special body area which was associated with worse QoL. Ixekizumab is similarly effective in reducing disease severity and improving QoL in patients with plaque psoriasis across different special body areas.

The Real-World Effectiveness and Tolerability of a Soothing Cream Containing the Postbiotic Aquaphilus dolomiae Extract-G2 for Skin Healing.

INTRODUCTION: In vitro and pre-marketing clinical data have shown the healing properties of a postbiotic extract from Aquaphilus dolomiae (ADE-G2). The effectiveness and tolerability of an ADE-G2-based cream were therefore evaluated for the management of minor skin impairment and wound healing in a large population of subjects in routine clinical practice. METHODS: A real-world, international, pre-post comparative study was conducted in infants, children, and adults with various types of superficial skin impairment who used the study product daily for around 3 weeks according to their dermatologist's advice. Immediate and follow-up changes in dermatologic signs and symptoms were assessed through clinical scoring. User satisfaction, overall product effectiveness, and tolerability were also evaluated. Analyses were performed in the whole study population and in subject subgroups according to skin impairment type and age. RESULTS: Overall, 1317 subjects (83.1% adults, 72.0% female) were included. Dermatologists reported effectiveness and "good" or "very good" tolerability of the cream in 93.8% (1221/1302) and 98.5% (1278/1297) of subjects, respectively. Immediate symptom relief after the first application was reported by 88.3% (849/962) of subjects. After several weeks of regular use (16.7 ± 11.6 days), dermatologic signs and symptoms significantly improved in the whole study population and in the subgroups, with mean decreases in severity scores ranging from -34.5% to -92.5% (p < 0.0001). The smallest improvements were found in subjects with oncologic treatment-related skin impairment. At study end, most users (> 95%) were "very satisfied" or "satisfied" with the cream and found that skin healing was rapid and of good quality. CONCLUSION: The ADE-G2-based cream proved to be effective and well tolerated in real-life conditions for the management of minor skin impairment in a large and varied cohort of subjects. This product, used as a standalone or adjunctive regimen, can help accelerate the healing of various types of superficial skin impairment.

Association between systemic immune inflammation index, systemic inflammation response index and adult psoriasis: evidence from NHANES.

Background: The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) are both novel biomarkers and predictors of inflammation. Psoriasis is a skin disease characterized by chronic inflammation. This study aimed to investigate the potential association between SII, SIRI, and adult psoriasis. Methods: Data of adults aged 20 to 80 years from the National Health and Nutrition Examination Survey (NHANES) (2003-2006, 2009-2014) were utilized. The K-means method was used to group SII and SIRI into low, medium, and high-level clusters. Additionally, SII or SIRI levels were categorized into three groups: low (1st-3rd quintiles), medium (4th quintile), and high (5th quintile). The association between SII-SIRI pattern, SII or SIRI individually, and psoriasis was assessed using multivariate logistic regression models. The results were presented as odds ratios (ORs) and confidence intervals (CIs). Restricted cubic spline (RCS) regression, subgroup, and interaction analyses were also conducted to explore the potential non-linear and independent relationships between natural log-transformed SII (lnSII) levels or SIRI levels and psoriasis, respectively. Results: Of the 18208 adults included in the study, 511 (2.81%) were diagnosed with psoriasis. Compared to the low-level group of the SII-SIRI pattern, participants in the medium-level group had a significantly higher risk for psoriasis (OR = 1.40, 95% CI: 1.09, 1.81, p-trend = 0.0031). In the analysis of SII or SIRI individually, both SII and SIRI were found to be positively associated with the risk of psoriasis (high vs. low group OR = 1.52, 95% CI: 1.18, 1.95, p-trend = 0.0014; OR = 1.48, 95% CI: 1.12, 1.95, p-trend = 0.007, respectively). Non-linear relationships were observed between lnSII/SIRI and psoriasis (both p-values for overall < 0.05, p-values for nonlinearity < 0.05). The association between SII levels and psoriasis was stronger in females, obese individuals, people with type 2 diabetes, and those without hypercholesterolemia. Conclusion: We observed positive associations between SII-SIRI pattern, SII, SIRI, and psoriasis among U.S. adults. Further well-designed studies are needed to gain a better understanding of these findings.

An AhR-Ovol1-Id1 regulatory axis in keratinocytes promotes skin homeostasis against atopic dermatitis.

Skin is our outer permeability and immune defense barrier against myriad external assaults. Aryl hydrocarbon receptor (AhR) senses environmental factors and regulates barrier robustness and immune homeostasis. AhR agonist is in clinical trial for atopic dermatitis (AD) treatment, but the underlying mechanism of action remains ill-defined. Here we report OVOL1/Ovol1 as a conserved and direct transcriptional target of AhR in epidermal keratinocytes. We show that OVOL1/Ovol1 impacts AhR regulation of keratinocyte gene expression, and Ovol1 deletion in keratinocytes hampers AhR's barrier promotion function and worsens AD-like inflammation. Mechanistically, we identify Ovol1's direct downstream targets genome-wide, and provide in vivo evidence for Id1's critical role in barrier maintenance and disease suppression. Furthermore, our findings reveal an IL-1/dermal γδT cell axis exacerbating both type 2 and type 3 immune responses downstream of barrier perturbation in Ovol1 -deficient AD skin. Finally, we present data suggesting the clinical relevance of OVOL1 and ID1 function in human AD. Our study highlights a keratinocyte-intrinsic AhR-Ovol1-Id1 regulatory axis that promotes both epidermal and immune homeostasis against AD-like inflammation, implicating new therapeutic targets for AD.

Better efficacy, lower recurrence rate and decreased CD8+TRM with guselkumab treatment for generalized pustular psoriasis: A prospective cohort study from China.

Generalized pustular psoriasis (GPP) is a severe and uncommon form of psoriasis, for which treatment options are limited. There is an urgent need to expand the treatment options for GPP. Currently, adalimumab, secukinumab, and guselkumab are considered effective for GPP, but there is a lack of prospective direct comparative studies on their efficacy for GPP. We conducted a prospective, single-center, observational study on 50 GPP patients to compare the efficacy, safety, and recurrence rates of these three biologics. Adalimumab, secukinumab, and guselkumab resulted in varying degrees of improvement in patients with GPP, but guselkumab exhibited superior efficacy and a lower recurrence rate than the other two drugs. This enhanced response may be attributed to the significant reduction in CD8+ tissue-resident memory T cells within GPP lesions caused by guselkumab.

Decreased risk of COVID-19 and long COVID in patients with psoriasis receiving IL-23 inhibitor: A cross-sectional cohort study from China.

Background: Although clinical trials and real-world data suggest that the risk of COVID-19 and its complications is not exacerbated in patients with psoriasis treated by biological agents, the evidence for this is still limited. Objectives: We aimed to assess the outcomes of COVID-19 among Chinese patients with psoriasis treated by IL-23 inhibitor, and to compare these variables in patients receiving other therapies. Methods: A cross-sectional cohort study was conducted to compare psoriasis treatment with IL-23 inhibitor to other treatment methods. All the patients received a questionnaire that contained questions about their psoriasis treatment, COVID-19 symptoms, and related risk factors. The prevalence of COVID-19 was calculated, and logistic regression analyses were performed to determine the association between treatment method and COVID-19 risk. The symptoms of COVID-19 and long COVID were described for each treatment group. Results: Between December 2022 and February 2023, 732 patients with psoriasis were included in the final analysis. 549 patients had a SARS-CoV-2 infection during the study period. Our results showed that individuals who worked outdoors had a decreased risk of COVID-19, as did those who had other allergic disease. With regard to the effect of the treatment regimens, IL-23 inhibitor treatment was associated with a decreased risk of COVID-19 compared to almost all the other treatments except acitretin. Fever was the most common symptom, but the maximum temperature and duration of fever were comparable among the treatment groups. Patients treated with IL-23 inhibitor were more likely to be asymptomatic after recovery compared to patients treated with methotrexate, narrow-bound ultra violet B, or TNF-α inhibitor. Conclusions: IL-23 inhibitor treatment may lower the risk of COVID-19 and long COVID. Thus, IL-23 inhibitor treatment might be beneficial and positively considered for patients with psoriasis who require systemic treatment during periods when there is a surge in COVID-19 cases.

A novel online calculator based on clinical features and hematological parameters to predict total skin clearance in patients with moderate to severe psoriasis.

BACKGROUND: Treatment responses to biologic agents vary between patients with moderate to severe psoriasis; while some patients achieve total skin clearance (TSC), a proportion of patients may only experience partial improvement. OBJECTIVE: This study was designed to identify potential predictors for achieving TSC in psoriasis patients treated with IL-17 inhibitors. It also aimed to develop an easy-to-use calculator incorporating these factors by the nomogram to predict TSC response. METHODS: A total of 381 patients with psoriasis receiving ixekizumab were included in the development cohort and 229 psoriasis patients who initiated secukinumab treatment were included in the validation cohort. The study endpoint was achieving TSC after 12 weeks of IL-17 inhibitors treatment, defined as the 100% improvement in Psoriasis Area and Severity Index (PASI 100). Multivariate Cox regression analyses and LASSO analysis were performed to identify clinical predictors and blood predictors respectively. RESULTS: The following parameters were identified as predictive factors associated with TSC: previous biologic treatment, joint involvement, genital area affected, early response (PASI 60 at week 4), neutrophil counts and uric acid levels. The nomogram model incorporating these factors achieved good discrimination in the development cohort (AUC, 0.721; 95% CI 0.670-0.773) and validation cohort (AUC, 0.715; 95% CI 0.665-0.760). The calibration curves exhibited a satisfactory fit, indicating the accuracy of the model. Furthermore, the decision curve analysis confirmed the clinical utility of the nomogram, highlighting its favorable value for practical application. Web-based online calculator has been developed to enhance the efficiency of clinical applications. CONCLUSIONS: This study developed a practical and clinically applicable nomogram model for the prediction of TSC in patients with moderate to severe psoriasis. The nomogram model demonstrated robust predictive performance and exhibited significant clinical utility. Trial registration A multi-center clinical study of systemic treatment strategies for psoriasis in Chinese population;ChiCTR2000036186; Registered 31 August 2020; https://www.chictr.org.cn/showproj.html?proj=58256 .

Characteristics of n6-methyladenosine (m6A) regulators and role of FTO/TNC in scleroderma.

BACKGROUND: m6A regulators have important roles in a variety of autoimmune diseases, but their potential function in scleroderma, a refractory connective tissue disease, remains unclear. Tenascin C (TNC) is known to be a factor promoting collagen deposition in the development of scleroderma, but the regulatory relationship between TNC and m6A regulators is unknown. METHODS: We extracted GSE33463 data consisting of forty-one healthy controls and sixty-one patients with scleroderma, and we analyzed the expression levels of twenty-one m6A regulators as well as the associations between them. In addition, we obtained random forest (RF) and nomogram models to predict the likehood of scleroderma. Next, we categorized the m6Aclusters and geneclusters by consensus clustering, and we performed an immune cell infiltration analysis for each cluster. Finally, we injected adenoviruses into a bleomycin (BLM)-induced mouse model of scleroderma, which was used to overexpress FTO and TNC. We assess the extent of skin fibrosis in the mice samples using pathology stains and measuring their hydroxyproline content and collagen mRNA. RESULTS: We initially identified fourteen differentially expressed m6A regulators (WTAP, RBM15, CBLL1, FTO, ALKBH5, YTHDC1, YTHDC2, YTHDF1, YTHDF2, YTHDF3, RBMX, HNRNPC, IGFBP1 and IGFBP2). We found ALKBH5 to be positively associated with CBLL1 and RBM15, and FTO to be negatively associated with WTAP. In addition, we identified four m6A regulators (CBLL1, IGFBP1, YTHDF2 and IGFBP2) using a RF model, and we designed a nomogram model with those variables that proved reliable according to the calibration curve and clinical impact curve. We found that the m6Acluster A was correlated with Type 1 T helper cell infiltration and the genecluster A was correlated with regulatory T cell infiltration. Finally, we showed that FTO overexpression downregulated the m6A and mRNA levels of TNC, and alleviated skin fibrosis in the mouse model of scleroderma. Thus, our overexpression experiments provide preliminary evidence suggesting that TNC is an adverse factor in scleroderma. CONCLUSION: Our approach might be useful as a new and accurate scleroderma diagnosis method. Moreover, our results suggested that FTO/TNC might be a novel scleroderma therapeutic target.

Long-term efficacy and safety of dupilumab for severe bullous pemphigoid: A prospective cohort study.

BACKGROUND: Bullous pemphigoid (BP) is a common subepidermal bullous disease. Dupilumab is a novel treatment for BP. However, its long-term efficacy and safety have not been demonstrated in prospective studies. OBJECTIVE: Evaluate the long-term efficacy and safety of dupilumab in treating severe BP. METHODS: Patients were divided into two groups: the methylprednisolone monotherapy group (M), and the methylprednisolone and dupilumab combination therapy group (D + M). This study consisted of two stages. The first stage focused on the initial treatment phase, where the early efficacy and safety was evaluated. The study then entered the 12-month maintenance treatment stage, where we assessed recurrence in both groups. Additionally, we evaluated the rate of healing of skin lesions, glucocorticoids burden and length of hospital stay and various laboratory test indicators. RESULTS: After four weeks of treatment, the Bullous Pemphigoid Disease Area Index (BPDAI) and pruritus Numerical Rating Scale scores of the D + M group decreased significantly more than those of the M group. The median BPDAI at week 4 was 0 (range: 0.0-3.0) in the D + M group and 10.0 (5.0-12.0) in the M group (P < 0.001). Patients treated with dupilumab experienced a faster cessation of new blisters, quicker glucocorticoid reduction, shorter healing times, and shorter hospital stays (P < 0.001). Additionally, after two weeks of treatment, the levels of eosinophils and immunoglobulin E also decreased (P < 0.001). Follow-up studies further demonstrated that dupilumab monotherapy was associated with a lower recurrence rate. Notably, no serious adverse effects were observed in the study. CONCLUSIONS: Our study provides evidence for the efficacy of dupilumab in the treatment of BP based on prospective studies. Additionally, our findings suggest that dupilumab can be considered a reliable single-agent maintenance treatment due to its good safety profile and lower relapse.