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关键词： Takayasu arteritis   large vessel vasculitis   retention rate   tocilizumab   TNF inhibitor   biologic agent  

摘要： Objective. We compared the drug retention rate of tumor necrosis factor (TNF) inhibitors (TNFi) and tocilizumab in Takayasu arteritis (TAK) as an index of balance between effectiveness and safety in a real-world setting. Method. We included 50 TAK patients who received biologics in nine hospitals. All patients fulfilled the 1990 American College of Rheumatology classification criteria for TAK. We retrospectively collected clinical information. We analyzed the drug retention rates and the reasons for discontinuation regarding TNFi and tocilizumab. Results. The prednisolone dose at the start of the first biologics was a median of 15 mg/day, and an immunosuppressant was used in 25 patients. Tocilizumab was the most frequent first biologics (64%). Twenty-seven of 32 patients continued on tocilizumab, and four of 18 patients continued on TNFi. The retention rate was significantly higher in tocilizumab than in TNFi (87.9% vs. 66.7% at one year, p = 0.024). The reasons for discontinuing tocilizumab were primary failure in two patients, and other reasons in three. The reasons for discontinuing TNFi were secondary failure in five patients, primary failure in four patients, and other reasons in five. Conclusion. Tocilizumab has a higher continuation rate than TNFi, suggesting that tocilizumab may have better benefit-risk balance for TAK patients.

关键词： IL-2 (interleukin-2)   T helper type 2 (Th2)   ILC2-group 2 innate lymphoid cell   dendritic cell (DC)   type 2 immunity  

摘要： Type 2 immune responses are essential for protective immunity against helminth parasites and for promoting tissue repair, but they can also drive allergic inflammation. T helper type 2 (Th2) cells and group 2 innate lymphoid cells (ILC2s) are key drivers of these responses, producing hallmark type 2 cytokines such as IL-4, IL-5, IL-9 and/or IL-13. While IL-2 has long been recognized as a T cell growth factor, emerging evidence reveals its central role in shaping Th2 cell fate and function. This review focuses on recent studies on how the availability of IL-2 is regulated in vivo for inducing Th2 cells. We also discuss the role of IL-2 in activating ILC2s and thereby linking innate and adaptive immune system in the context of type 2 immunity. Together, the studies discussed here highlight the role of IL-2 as a spatially and functionally dynamic coordinator of type 2 immunity.

关键词： Anti-IL-23   biologics   guselkumab   psoriasis   risankizumab   super-responder   tildrakizumab  

摘要： Background/Objectives: Psoriasis is a chronic immune-mediated skin disease with an estimated global prevalence of 3%. Real-world studies have demonstrated that biologic therapies have transformed the management of moderate-to-severe psoriasis by providing optimal disease control and a favorable safety profile. However, a new challenge lies in identifying those most likely to achieve an early and sustained response, defined as 'super-responders' (SRs). This is particularly relevant given recent evidence suggesting that IL-23 inhibitors may have long-term disease-modifying effects by acting on tissue-resident memory T cells. Identifying positive and negative baseline predictors associated with achieving SR status in patients treated with anti-IL-23 agents. Methods: This retrospective observational study analyzed data from the electronic medical records of IRCCS Humanitas Research Hospital between June 2021 and June 2025. A total of 611 patients with moderate-to-severe psoriasis who were treated with risankizumab, guselkumab or tildrakizumab were included in the study. Clinical assessments were conducted at baseline and weeks 16, 28 and 52. SR status was defined as achieving a PASI score of <= 1 at week 16, with this score being maintained through weeks 28 and 52. Results: Of the 611 enrolled patients, 390 (63.8 %) achieved SR status. In multivariate logistic regression, disease duration <= 2 years was the strongest independent predictor (Odds Ratio [OR] 2.47, p = 0.025), followed by bio-na & iuml;ve status (OR 1.53, p = 0.019). Obesity (OR 0.71, 95 % CI 0.45-1.13) and cardiometabolic comorbidities (OR 0.93, 95 % CI 0.63-1.38) were not significantly associated with response after adjustments. No serious adverse events or treatment discontinuations occurred during 52 weeks of follow-up. Conclusions: Shorter disease duration (<= 2 years) and bio-na & iuml;ve status were identified as independent predictors of SR status. Identifying these patients could inform the develop

关键词： artificial intelligence   cytokines   IFN   IL-33   IL-4   machine learning   mast cells   omics   TGF beta   transcriptomics  

摘要： Mast cells (MCs) rapidly adapt to the microenvironment due to the plethora of cytokine receptors expressed. Understanding microenvironment-primed immune responses is essential to elucidate the phenotypic/functional changes MCs undergo, and thus understand their contribution to diseases and predict the most effective therapeutic strategies. We exposed primary human MCs to cytokines mimicking a T1/pro-inflammatory (IFN gamma), T2/allergic (IL-4 + IL-13), alarmin-rich (IL-33) and pro-fibrotic/pro-tolerogenic (TGF beta) microenvironment. We investigated MC surface receptor expression, activation, cytokine, histamine, and prostaglandin D2 release, and performed transcriptomics to define shared and unique genetic features. Using machine learning, we extracted minimal cytokine-activated signatures and performed gene set variation analysis (GSVA), single-cell clustering, and pseudotime analyses on tissue MCs from skin and respiratory diseases. MCs exposed in vitro to IFN gamma acquire an antigen-presenting phenotype (HLA-DR+), increase IgE-mediated responses and histamine release, while TGF beta inhibits activation and boosts integrin alpha v beta 3 expression. IL-33 primarily drives cytokine (GM-CSF, IL-5, IL-10, IL-13) and chemokine production (IL-8, MCP-1, MIP-1 alpha) and facilitates mixed IgG-IgE responses. Among uniquely expressed genes, 245 were highly informative to discriminate cytokine-primed MCs. GSVA revealed MC IL-4 + IL-13 signatures enriched in atopic dermatitis and psoriasis, IFN gamma in COVID-19 infection and cystic fibrosis, IL-33 in COVID-19 and chronic obstructive pulmonary disease (COPD) and TGF beta in pulmonary fibrosis (PF) and chronic rhinosinusitis. Furthermore, we detected positive IL-33/TGF beta priming in eosinophil-high COPD. Minimal cytokine-activated signatures identified disease-cytokine-specific MC clusters and pseudotime trajectories, suggesting involvement of MCs in fibrosis (COPD/PF), T1/alarmin-driven inflammation (COVID-19) and mixed

摘要： Psoriasis is a chronic skin disease that results in scaly patches and affects 2-3% of people worldwide. Therapeutic treatment targets the TNF-α/IL-17 axis to disrupt keratinocyte hyperproliferation and inflammation. While more is known about the role of dermal αß and γδ T cells in IL-17 production, less is understood about the role of resident epidermal T cells. Here, we examine how TNF-α modulates epidermal γδ T cell activation and function. We show that a subset of activated epidermal γδ T cells expresses TNFR2 with or without TNFR1. Stimulation with TNF-α induces epidermal γδ T cells to produce IL-17 family cytokines and chemokines. Epidermal γδ T cells do not require TNFR1 or 2 for development or homing to the skin. Instead, TNFR2 plays roles in epidermal γδ T cell function skewing them toward a Tγδ17 phenotype during psoriasis. Investigation of the mechanisms by which TNF-α associated inflammation impacts epidermal γδ T cell function may help identify new cellular targets for immunotherapy or mark them as early regulators of skin inflammation.

关键词： sepsis   interleukin-10   lymphocyte count   lactate   prognosis prediction   risk stratification  

摘要： Background: Sepsis is a highly heterogeneous clinical syndrome, and the real-time prognosis prediction and risk stratification for it remain a big challenge in current clinical research. This study aimed to assess the performance of IL-10/lymphocyte ratio (ILR) and lactate (Lac) in the prognostic prediction and risk stratification of sepsis. Methods: This is a retrospective observational study that included 148 patients with sepsis admitted to the First Affiliated Hospital of Chongqing Medical University from January 2022 to February 2023. Data collection commenced on the first day of ICU admission, with clinical and laboratory parameters recorded within 24 h of diagnosis, including IL-10 levels, lymphocyte counts, Lac, SOFA score, and APACHE II score. The relationship between ILR and Lac and 28-day mortality were analyzed by multivariate logistic regression analysis and Cox proportional hazards regression, and their predictive efficacy were assessed by receiver operator characteristic curves (ROCs), and Kaplan-Meier survival curves were used to validate the effect of risk stratification. Results: Patients in the death group exhibited significantly higher ILR (302.33 vs. 16.37) and Lac levels (3.25 mmol/L vs. 1.90 mmol/L) compared to the survival group (both p < 0.001). Multivariate logistic regression analysis showed that ILR (OR = 1.005, 95% CI 1.001-1.009) was independent risk factor for death at 28 days. Analysis of ROCs showed that the predictive efficacy of ILR (AUC = 0.860) was superior to the APACHE II score (AUC = 0.797) and the SOFA score (AUC = 0.704). Based on stratification by ILR (cutoff value 97.4) and Lac (cutoff value 4.1 mmol/L), the four risk stratification levels (Levels I-IV) exhibited progressively decreasing 28-day mortality rates: Level I (78.95%), Level II (50.00%), Level III (15.38%), and Level IV (7.69%). Kaplan-Meier analysis confirmed significant survival differences (p < 0.001), with Level I demonstrating the worst prognosis. Conclusion

关键词： Chemical activation  

摘要： Regulatory Treg cells are essential for immune homeostasis. While CD4 Treg cells are well characterized, CD8 Treg cells remain less understood and are primarily observed in pathological or experimental contexts. Here, we identify a naturally occurring CD8 regulatory precursor Trp cell at the steady state, defined by a CD8+HLA-DR+CD27+ phenotype and a transcriptome resembling CD4 Treg cells. Multiomics analyses reveal activation of TCF7 and costimulatory and co-inhibitory molecules in CD8 Trp cells. CD8 Trp cells suppress T cell expansion in vitro and in vivo. In a humanized xenogeneic graft-versus-host disease (GVHD) model, they dampen T cell activation, alleviate GVHD pathology, and prolong survival without impairing antileukemia activity. Mechanistically, CD8 Trp cells promote immune regulation by inducing FOXP3 expression in both CD4 Treg cells and themselves. Their expansion also correlates with immune homeostasis restoration post-allogeneic stem cell transplantation. These findings establish CD8 Trp cells as a naturally occurring regulatory precursor population that promotes transplantation tolerance.

关键词： Adenoid hypertrophy   Interferon-gamma   CD-56   Otitis media with effusion   Tonsillar hyperplasia   Children   Immunohistochemistry  

摘要： This study aims to investigate the histopathological expression of Interferon-gamma (IFN-gamma) and CD-56 in pediatric patients who underwent surgery for adenoid hypertrophy, and to evaluate their association with coexisting otitis media with effusion (OME) and tonsillar hypertrophy. A total of 100 children who underwent adenoidectomy, adenotonsillectomy, adenoidectomy with ventilation tube insertion, or adenotonsillectomy with ventilation tube insertion were included and divided into four equal groups. Surgical specimens were stained with hematoxylin-eosin, CD-56, and IFN-gamma. Clinical data including age, sex, comorbidities, adenoid volume, tonsil grade, and presence of OME were analyzed. Immunohistochemical staining rates were compared among the groups. The rate of IFN-gamma staining was significantly higher in the group that underwent adenotonsillectomy with ventilation tube insertion compared to other groups (p < 0.05). A statistically significant increase in IFN-gamma staining was also observed in patients with OME (p < 0.05). CD-56 staining did not show significant differences among the groups (p > 0.05). The elevated IFN-gamma expression in patients with OME and tonsillar hypertrophy may indicate an active inflammatory response. These findings suggest that IFN-gamma may play a role in the pathogenesis of OME in children with adenoid hypertrophy and could be considered as a potential therapeutic target.

关键词： tumor necrosis factors   cancer   infections   antagonists   inflammatory disorders   janus kinases   tumor necrosis factor inhibitors   venous thromboembolism   comparative effectiveness research   janus kinase inhibitors   adverse event   cardiovascular event  

摘要： Importance Janus kinase (JAK) inhibitors are highly effective medications for several immune-mediated inflammatory diseases (IMIDs). However, safety concerns have led to regulatory restrictions. Objective To compare the risk of adverse events with JAK inhibitors vs tumor necrosis factor (TNF) antagonists in patients with IMIDs in head-to-head comparative effectiveness studies. Data Sources For this systematic review and meta-analysis, the Ovid Medline, Ovid EMBASE, and Web of Science databases were searched from inception to June 25, 2025. Study Selection Head-to-head comparative effectiveness studies of adults (aged >= 18 years) with IMIDs (including rheumatoid arthritis, inflammatory bowel disease, psoriasis or psoriatic arthritis, or spondyloarthropathy) treated with either JAK inhibitors or TNF antagonists were included. Randomized clinical trials, noncomparative observational studies, studies not reporting outcomes of interest or focused solely on specific safety events, and studies with a sample size of less than 500 were excluded. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was followed. Data Extraction and Synthesis Four investigators independently, and in pairs, abstracted data from included studies. A random-effects meta-analysis was conducted to obtain incidence rates (IRs) and hazard ratios (HRs) for JAK inhibitors vs TNF antagonists for each safety outcome (serious infections, malignant neoplasms, major cardiovascular events [MACEs], or venous thromboembolism [VTE]), adjusting for key confounding variables. Heterogeneity was quantified using the I2 statistic. Risk of bias was assessed by 2 investigators independently using the Newcastle-Ottawa Scale. Main Outcomes and Measures The primary outcome was risk of serious infections, malignant neoplasms, MACEs, or VTE. Results This meta-analysis of 42 studies with low to moderate risk of bias included 813 881 patients (median age, 55.7 years [IQR, 53.0-5

关键词： 胞内劳森菌   单克隆抗体   阻断ELISA   重组MltA蛋白  

摘要： 本研究旨在建立一种检测胞内劳森菌（Lawsonia intracellularis）抗体的阻断ELISA方法。采用原核表达的胞内劳森菌重组MltA蛋白免疫小鼠，制备获得单克隆抗体，通过Western blot和间接免疫荧光（IFA）鉴定了单克隆抗体的特异性。以重组蛋白MltA为包被抗原，待检血清为一抗，建立了检测胞内劳森菌抗体的阻断ELISA方法。确定了阻断ELISA方法最佳反应条件，并对方法的灵敏度、特异性、重复性及符合率进行分析。结果显示: 所建立方法的灵敏度和特异性分析显示在胞内劳森菌阳性血清稀释度为1:4时仍可稳定检出阳性，且与猪流行性腹泻病毒、伪狂犬病病毒及大肠杆菌阳性血清无交叉反应；重复性试验结果显示，批内重复试验的变异系数为1.4％～9.3％，批间重复试验的变异系数为1.0％～9.6％；与IFA结果对比，本研究所建立方法的敏感性为95.91%，特异性为80.65%，总符合率为85.92%。本研究对胞内劳森菌外膜蛋白MltA进行原核表达和纯化，制备了针对MltA的单克隆抗体，建立了一种检测胞内劳森菌抗体的阻断ELISA方法，可用于猪增生性肠病的临床诊断。