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Risk Factors of Progression to Active Tuberculosis in Rheumatic Patients With Latent Tuberculosis: A Retrospective Study 风湿合并潜伏结核患者进展为活动性结核的危险因素:一项回顾性研究。
IF 2.7 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-10-15 DOI: 10.1002/iid3.70270
Fengjuan Wang, Lei Zhou, Xiaoyan Hao, Jiayun Liu

Background

In rheumatism patients, the immune system erroneously attacks the body′s own tissues. This impairs the body′s defense against external pathogens and is a contributing factor to the occurrence of tuberculosis infection. The primary objective of this investigation was to examine the risk factors for the progression from latent tuberculosis infection (LTBI) to active tuberculosis (ATB) in patients with rheumatic diseases (RD).

Methods

RD cover a wide range of disorders affecting the skeletal system, joints, and adjacent soft tissues. When the human body is infected by Mycobacterium tuberculosis, the condition is classified as either LTBI or ATB, depending on the presence or absence of typical clinical symptoms. A retrospective study was conducted at the Xijing Hospital of the Fourth Military Medical University. Specifically, the Laboratory Information System was used to investigate patients diagnosed with RD from January 2012 to October 2022.

Results

The study included a total of 32,235 individuals diagnosed with rheumatism, of whom only 18.60% were screened for LTBI. The overall incidence of LTBI was 25.33%. Among the 629 RD inpatients with LTBI, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) accounted for half, and 56.44% received glucocorticoid (GC) therapy. Risk-factor assessment for ATB was conducted in 247 cases. A GC dose of 20 mg/day or more was an independent risk factor for LTBI activation (odds ratio = 3.59, 95% CI: 1.26–10.29, p = 0.017).

Conclusion

In China, RD patients have a relatively high risk of LTBI. In clinical practice, LTBI screening should be routinely performed for RD patients before initiating GC therapy at a dose of ≥ 20 mg/day. For patients with SLE and RA undergoing continuous GC treatment, close monitoring is essential. In addition, clinicians should enhance the diagnostic pathways and treatment management for these patients to prevent the occurrence of ATB.

背景:在风湿病患者中,免疫系统错误地攻击身体自身组织。这损害了身体对外部病原体的防御,是结核病感染发生的一个因素。本研究的主要目的是研究风湿性疾病(RD)患者从潜伏性结核感染(LTBI)发展为活动性结核(ATB)的危险因素。方法:RD涵盖了广泛的影响骨骼系统、关节和邻近软组织的疾病。当人体感染结核分枝杆菌时,根据是否存在典型的临床症状,将病情分类为LTBI或ATB。回顾性研究在第四军医大学西京医院进行。具体而言,使用实验室信息系统调查2012年1月至2022年10月诊断为RD的患者。结果:该研究共包括32,235名被诊断为风湿病的个体,其中只有18.60%进行了LTBI筛查。LTBI的总发生率为25.33%。629例RD合并LTBI住院患者中,系统性红斑狼疮(SLE)和类风湿关节炎(RA)占一半,接受糖皮质激素(GC)治疗的占56.44%。对247例ATB进行危险因素评估。20mg /天以上的GC剂量是LTBI激活的独立危险因素(优势比= 3.59,95% CI: 1.26-10.29, p = 0.017)。结论:在中国,RD患者发生LTBI的风险较高。在临床实践中,在开始≥20mg /天的GC治疗前,RD患者应常规进行LTBI筛查。对于持续接受GC治疗的SLE和RA患者,密切监测是必不可少的。此外,临床医生应加强对这些患者的诊断途径和治疗管理,以防止ATB的发生。
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引用次数: 0
Generalized Modules for Membrane Antigens (GMMA) Elicit Mild Local Reactogenicity After Intramuscular Injection in Absence of Aluminum Salt Adjuvant 在没有铝盐佐剂的情况下,肌内注射膜抗原通用模块(GMMA)引起轻度局部反应性。
IF 2.7 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-10-15 DOI: 10.1002/iid3.70278
Raffaella Cecchi, Silvia Maccari, Renzo Alfini, Roberta Di Benedetto, Simona Gallorini, Elena Cartocci, Sara Marchi, Giacomo Romagnoli, Erika Bartolini, Francesca Micoli, Diego Piccioli

Background and Objectives

Generalized modules for membrane antigens (GMMA) are outer membrane vesicles derived from gram-negative bacteria that can be used to design affordable subunit vaccines. GMMA are highly immunogenic and capable to induce an optimal antigen-specific humoral immune response both in animals and humans. Despite their potent immunogenicity, GMMA are usually formulated with aluminum salts (alum) to reduce their potential systemic reactogenicity. GMMA, in fact, contain agonists of toll-like receptor 4 (TLR4) and TLR2 that possess pro-inflammatory activity. The adsorption of GMMA onto alum is believed to reduce their systemic exposure. However, it has been found that GMMA formulated without alum did not induce concerning signs of systemic reactogenicity in the rabbit model. Here, we asked whether GMMA promote local reactogenicity.

Methods

We immunized mice intramuscularly with GMMA alone or adsorbed to alum and analyzed the injection site during 7 days after treatment.

Results

We found that GMMA alone promoted only mild inflammation within the muscle, whereas the presence of alum induced severe muscle inflammation, as expected. Thus, in the mouse model, GMMA demonstrated to possess mild local reactogenic potential, while alum is confirmed a major driver of local reactogenicity.

Conclusion

Our results further support the idea to investigate the reactogenicity of GMMA formulated without alum in clinical studies.

背景和目的:膜抗原通用模块(GMMA)是源自革兰氏阴性菌的外膜囊泡,可用于设计可负担得起的亚单位疫苗。GMMA具有高度的免疫原性,能够在动物和人类中诱导最佳的抗原特异性体液免疫反应。尽管具有强大的免疫原性,GMMA通常与铝盐(明矾)配制,以减少其潜在的全身反应原性。事实上,GMMA含有toll样受体4 (TLR4)和TLR2激动剂,具有促炎活性。GMMA在明矾上的吸附被认为可以减少它们的全身暴露。然而,已经发现不含明矾的GMMA在兔模型中没有引起全身反应性的迹象。在这里,我们询问GMMA是否会促进局部反应性。方法:分别用GMMA单独或吸附在明矾上对小鼠进行肌肉免疫,并在给药后7天对注射部位进行分析。结果:我们发现GMMA单独仅促进肌肉内轻度炎症,而明矾的存在引起严重的肌肉炎症,正如预期的那样。因此,在小鼠模型中,GMMA被证明具有轻微的局部反应性,而明矾被证实是局部反应性的主要驱动因素。结论:本研究结果进一步支持在临床研究中研究不含明矾配制的GMMA的反应性。
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引用次数: 0
Serum Levels of 54 Cytokines and Chemokines Reveal Distinct Inflammatory Signatures in Ankylosing Spondylitis 强直性脊柱炎患者血清54种细胞因子和趋化因子水平显示不同炎症特征。
IF 2.7 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-10-15 DOI: 10.1002/iid3.70276
Huan Li, Ting Wang, Mingze Li, Wei Su, Ying Lv, Jialing Xiao, Xiaoxin Guo, Kai Dong, Chengzi Gan, Jing Zhu, Bo Gong

Background

Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disorder predominantly involving the axial skeleton. Understanding the cytokine and chemokine signatures in AS is crucial for elucidating disease mechanisms and identifying potential diagnostic biomarkers.

Methods

Serum samples from 31 AS patients and 20 age-matched healthy controls (HCs) were analyzed. The concentrations of 54 cytokines, chemokines, and angiogenesis-related factors were measured using a Meso Scale Discovery (MSD) electrochemiluminescence immunoassay. Data analysis included statistical comparison of serum cytokine levels, heatmap clustering, principal component analysis (PCA), and receiver operating characteristic (ROC) curve analysis. Validation was performed using peripheral blood mononuclear cells (PBMCs) from SKG mice, a spontaneous animal model of AS, through quantitative real-time PCR.

Results

Compared with HCs, AS patients showed significantly higher serum concentrations of 12 cytokines (TNF-α, TNF-β, IL-17A, IL-17D, VEGFA, ICAM1, SAA, IP-10/CXCL10, MIP-3α/CCL20, sFlt-1/VEGFR-1, CRP, and MCP-4/CCL13) and significantly lower concentrations of nine cytokines (IL-4, IL-8, IL-17C, MIP-1α/CCL3, eotaxin-3/CCL26, PlGF, VEGF-C, VEGF-D, and bFGF) (all p < 0.05). Heatmap clustering and PCA demonstrated a clear separation between AS patients and HCs. ROC curve analysis showed excellent diagnostic accuracy for IP-10/CXCL10 (AUC = 1.00), VEGF-D (AUC = 0.98), IL-17A (AUC = 0.87), TNF-α (AUC = 0.85), and ICAM1 (AUC = 0.84). Positive correlations were observed between IL-17A and MIP-3α/CCL20, and between VEGFA and sFlt-1, indicating coordinated inflammatory and angiogenic pathways. Validation experiments in SKG mice confirmed elevated IP-10/CXCL10 and reduced VEGF-D expression, supporting cross-species relevance.

Conclusions

This study identified distinct cytokine and chemokine profiles in AS patients. IP-10/CXCL10 and VEGF-D emerged as promising diagnostic biomarkers with high discriminatory power. Several previously unreported immune mediators were also highlighted. These findings provide new insights into AS pathogenesis and suggest potential targets for future therapeutic interventions.

背景:强直性脊柱炎(AS)是一种主要累及中轴骨骼的慢性自身免疫性炎症性疾病。了解AS中的细胞因子和趋化因子特征对于阐明疾病机制和识别潜在的诊断生物标志物至关重要。方法:分析31例AS患者和20例年龄匹配的健康对照(hc)的血清样本。使用Meso Scale Discovery (MSD)电化学发光免疫分析法测量54种细胞因子、趋化因子和血管生成相关因子的浓度。数据分析包括血清细胞因子水平的统计比较、热图聚类、主成分分析(PCA)和受试者工作特征(ROC)曲线分析。利用自发性AS动物模型SKG小鼠外周血单个核细胞(PBMCs),通过实时荧光定量PCR进行验证。结果:与hcc患者相比,AS患者血清中12种细胞因子(TNF-α、TNF-β、IL-17A、IL-17D、VEGFA、ICAM1、SAA、IP-10/CXCL10、MIP-3α/CCL20、sFlt-1/VEGFR-1、CRP和MCP-4/CCL13)浓度显著升高,9种细胞因子(IL-4、IL-8、IL-17C、MIP-1α/CCL3、eotaxin-3/CCL26、PlGF、VEGF-C、VEGF-D和bFGF)浓度显著降低(均为p)。IP-10/CXCL10和VEGF-D被认为是有前途的诊断性生物标志物,具有很高的鉴别能力。一些以前未报道的免疫介质也被强调。这些发现为AS的发病机制提供了新的见解,并提出了未来治疗干预的潜在靶点。
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引用次数: 0
Similarities and Differences in the Immune Characteristics of Intestinal Gamma Delta T Cells From Patients With Crohn's Disease and Ulcerative Colitis and Their Correlation With Disease Activity 克罗恩病和溃疡性结肠炎患者肠道γ δ T细胞免疫特性的异同及其与疾病活动度的相关性
IF 2.7 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-10-15 DOI: 10.1002/iid3.70273
Yujie Jiang, Linna Ye, Caixia Sheng, Jia Zhu, Jiaqi Xu, Xiaoqing Cheng, Guoxiang Fu, Zhinong Jiang

Background

Intestinal γδ T-cell immune characteristics and their relationship with disease activity in Crohn's disease (CD) and ulcerative colitis (UC) remain to be fully clarified.

Methods

Biopsies from 21 CD, 21 UC and 21 healthy controls were analyzed by flow cytometry for γδ T-cell frequency, cytotoxicity (perforin, granzyme-B), activation (HLA-DR) and exhaustion (PD-1). ROC curves were used to evaluate the diagnostic performance of these indices. Vγ subsets were profiled using published scRNA-seq data.

Results

As disease activity increased, intestinal γδ T cells in CD and UC patients decreased and could not activate. The differences were that the cytotoxicity of intestinal γδ T cells in CD patients was always normal as disease activity increased. In contrast, the cytotoxicity of intestinal γδ T cells in UC patients was suppressed. Different Vγ subsets in CD or UC patients showed different immune characteristics, which might lead to different immune characteristics of γδT cells in CD or UC patients at different disease active stages. Furthermore, γδ T cell and HLA-DR+ γδ T cell ratio were good indicators in diagnosing CD. The ratios of γδ T cell, HLA-DR+ γδ T cell, PD-1+ γδ T cell, and Perforin+ γδ T cell exhibited values for diagnosing UC. PD-1+ γδ T cell ratio was a valuable indicator to help distinguish CD from UC.

Conclusion

Intestinal γδ T cells exhibit both shared and divergent features in CD and UC that closely parallel disease activity, supporting their potential as immune biomarkers for diagnosis and discrimination between the two diseases.

背景:肠γδ t细胞免疫特性及其与克罗恩病(CD)和溃疡性结肠炎(UC)疾病活动性的关系尚不完全清楚。方法:采用流式细胞术分析21例CD、21例UC和21例健康对照的活检组织中γδ t细胞频率、细胞毒性(穿孔素、颗粒酶- b)、活化(HLA-DR)和衰竭(PD-1)。采用ROC曲线评价这些指标的诊断效能。使用公开的scRNA-seq数据分析Vγ亚群。结果:随着疾病活动性的增加,CD和UC患者肠道γδ T细胞减少,不能活化。不同的是,随着疾病活动度的增加,CD患者肠道γδ T细胞的细胞毒性始终是正常的。相比之下,UC患者肠道γδ T细胞的细胞毒性受到抑制。CD或UC患者不同的Vγ亚群表现出不同的免疫特性,这可能导致CD或UC患者不同疾病活动期γδT细胞的免疫特性不同。此外,γδ T细胞和HLA-DR+ γδ T细胞比值是诊断CD的较好指标,其中γδ T细胞、HLA-DR+ γδ T细胞、PD-1+ γδ T细胞和Perforin+ γδ T细胞比值对UC有诊断价值。PD-1+ γδ T细胞比值是鉴别CD与UC的重要指标。结论:肠道γδ T细胞在CD和UC中表现出共同和不同的特征,这些特征与疾病活动密切相关,支持它们作为诊断和区分两种疾病的免疫生物标志物的潜力。
{"title":"Similarities and Differences in the Immune Characteristics of Intestinal Gamma Delta T Cells From Patients With Crohn's Disease and Ulcerative Colitis and Their Correlation With Disease Activity","authors":"Yujie Jiang,&nbsp;Linna Ye,&nbsp;Caixia Sheng,&nbsp;Jia Zhu,&nbsp;Jiaqi Xu,&nbsp;Xiaoqing Cheng,&nbsp;Guoxiang Fu,&nbsp;Zhinong Jiang","doi":"10.1002/iid3.70273","DOIUrl":"10.1002/iid3.70273","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intestinal γδ T-cell immune characteristics and their relationship with disease activity in Crohn's disease (CD) and ulcerative colitis (UC) remain to be fully clarified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Biopsies from 21 CD, 21 UC and 21 healthy controls were analyzed by flow cytometry for γδ T-cell frequency, cytotoxicity (perforin, granzyme-B), activation (HLA-DR) and exhaustion (PD-1). ROC curves were used to evaluate the diagnostic performance of these indices. Vγ subsets were profiled using published scRNA-seq data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>As disease activity increased, intestinal γδ T cells in CD and UC patients decreased and could not activate. The differences were that the cytotoxicity of intestinal γδ T cells in CD patients was always normal as disease activity increased. In contrast, the cytotoxicity of intestinal γδ T cells in UC patients was suppressed. Different Vγ subsets in CD or UC patients showed different immune characteristics, which might lead to different immune characteristics of γδT cells in CD or UC patients at different disease active stages. Furthermore, γδ T cell and HLA-DR+ γδ T cell ratio were good indicators in diagnosing CD. The ratios of γδ T cell, HLA-DR+ γδ T cell, PD-1+ γδ T cell, and Perforin+ γδ T cell exhibited values for diagnosing UC. PD-1+ γδ T cell ratio was a valuable indicator to help distinguish CD from UC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Intestinal γδ T cells exhibit both shared and divergent features in CD and UC that closely parallel disease activity, supporting their potential as immune biomarkers for diagnosis and discrimination between the two diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 10","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12521879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Predictive Value of Combined CRP and INR for Intracranial Hypertension in Cerebral Venous Thrombosis CRP与INR联合检测颅内高压并发脑静脉血栓的预测价值。
IF 2.7 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-10-15 DOI: 10.1002/iid3.70265
Jiahui Yan, Manli Lu, Zhichao Huang, Yingying Xu, Yongjun Cao, Jianqiang Ni, Xia Zhang

Background

Intracranial hypertension (IH) is a frequently observed clinical manifestation of cerebral venous thrombosis (CVT), which reflects the severity of the disease. The gold standard of intracranial pressure (ICP) is through invasive lumbar puncture.

Objectives

We aimed to develop a noninvasive model combining biomarkers and clinical features to predict IH in CVT patients, facilitating early risk stratification.

Methods

The patients with CVT were consecutively enrolled in the Second Affiliated Hospital of Soochow University and the First Affiliated Hospital of Soochow University between January 2011 and June 2024, which were divided into two groups: CVT-IH group and CVT + IH group based on ICP levels. Additionally, participants were further categorized into four groups according to the cut-off of C-reactive protein (CRP) and international normalized ratio (INR) by the receiver operating characteristic (ROC) curves. Logistic regression models were employed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of IH across the four subgroups.

Results

157 individuals were finally included, 61 of whom had IH. Participants with CRP > 5.5 g/L or INR < 0.99 were more likely to experience IH. Those with high CRP and low INR conferred 9.778 times higher risk of IH compared with that of those with low CRP and high INR. Simultaneously adding CRP and INR to the basic model with established risk factors significantly improved risk discrimination and reclassification for IH of CVT patients.

Conclusions

Combination of CRP and INR better predicted the occurrence of IH for CVT patients, which might provide a noninvasive way of assessing ICP of CVT patients.

背景:颅内高压(Intracranial hypertension, IH)是脑静脉血栓形成(cerebral venous thrombosis, CVT)常见的临床表现,反映了该疾病的严重程度。颅内压(ICP)的金标准是通过有创腰椎穿刺。目的:我们旨在建立一种结合生物标志物和临床特征的无创模型来预测CVT患者的IH,促进早期风险分层。方法:于2011年1月至2024年6月连续入选东吴大学第二附属医院和东吴大学第一附属医院CVT患者,根据ICP水平分为CVT-IH组和CVT + IH组。此外,根据受试者工作特征(ROC)曲线的c反应蛋白(CRP)和国际标准化比率(INR)的截止值将参与者进一步分为四组。采用Logistic回归模型计算四个亚组IH的优势比(ORs)和95%置信区间(ci)。结果:最终纳入157人,其中61人患有IH。结论:CRP与INR联合应用能更好地预测CVT患者IH的发生,为CVT患者ICP的评估提供了一种无创方法。
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引用次数: 0
Dust Mite Serodominance Profiles in Lugo 卢戈地区尘螨血清优势度分析。
IF 2.7 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-10-15 DOI: 10.1002/iid3.70254
Francisco Carballada, Luis Alfredo González, Ramón Núñez, Raquel Lopez, Joaquín Martín, Nicola Giangrande, Antonio García-Dumpierrez, Javier Alcover, David Rodríguez, Ricardo Palacios

Introduction

House dust mite allergy affects 65–130 million people worldwide. Untreated patients could develop severe allergic diseases such as atopic dermatitis and asthma.

Methods

We consecutively recruited 50 patients with a clinical diagnosis of allergic rhinitis/rhino conjunctivitis. Mite Skin Prick Tests were performed. Mite specific IgE were tested.

Results

Ninety-six per cent of the patients had a positive prick test for Dpt, Dfar 94%, Ldt 86%, Tput 82%, and Blot 82%. Der p1 was recognized by 70%, Der p2 84%, Der p23 72%. Regarding serodominances, Der p2 was the highest one (30.2 kU/L). Forty-three patients presented sensitization to 3 Dermatophagoides pteronyssinus molecules, been 1 + 2 + 23 the main combination. Der p 1, 2, and 23 prevalence were similar in patients with intermittent or persistent allergic rhinitis. All patients with asthma recognized to Der p2 and more than 80% Der p1 and 23. In the group of patients without asthma, sensitivity to Der p23 is considerably reduced.

Conclusion

Ninety per cent of patients recognize Der p1, 2, and 23, alone or in any of their combinations. The high prevalence of sensitization to Der p23 (72%) stands out, that all asthmatic patients are sensitive to Der p2 and that sensitization to Der p23 in non-asthmatic patients drops to 50%.

导读:屋尘螨过敏影响全球6500 - 1.3亿人。未经治疗的患者可能会患上严重的过敏性疾病,如特应性皮炎和哮喘。方法:我们连续招募50例临床诊断为变应性鼻炎/犀牛结膜炎的患者。进行螨虫皮肤点刺试验。检测螨特异性IgE。结果:Dpt针刺试验阳性96%,Dfar阳性94%,Ldt阳性86%,Tput阳性82%,Blot阳性82%。Der p1的识别率为70%,Der p2为84%,Der p23为72%。血清优势度以Der p2最高(30.2 kU/L)。43例患者对3种鸡翅飞甲分子致敏,以1 + 2 + 23为主。在间歇性或持续性变应性鼻炎患者中,Der p 1、2和23的患病率相似。所有哮喘患者均可识别为Der p2,且80%以上为Der p1和Der 23。在没有哮喘的患者组中,对Der p23的敏感性明显降低。结论:90%的患者可以单独或联合识别Der p1、2和23。Der p23致敏率高(72%),所有哮喘患者均对Der p2敏感,非哮喘患者对Der p23致敏率降至50%。
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引用次数: 0
Revealing VNN1: An Emerging and Promising Target for Inflammation and Redox Balance 揭示VNN1:炎症和氧化还原平衡的新兴和有希望的靶标。
IF 2.7 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-10-15 DOI: 10.1002/iid3.70274
Linxi Lv, Tian Wang, Wenzhan Xie, Jialong Wei, Laixian Zhou, Xiaopei Qiu, Hui Feng, Wei Gu

Introduction

The intricate balance between immunometabolic homeostasis and redox equilibrium is crucial for maintaining health, and its dysregulation is implicated in a wide spectrum of diseases. Vascular non-inflammatory molecule-1 (VNN1) is an emerging pantetheinase that sits at the crossroads of inflammation and metabolism, yet a comprehensive review that synthesizes its tissue- and disease-specific roles and systematically evaluates its potential as a therapeutic target remains lacking.

Methods

A systematic literature search was conducted to identify relevant domestic and international studies on VNN1. The search included databases such as PubMed using keywords related to VNN1′s structure and function, the disease roles of its metabolites (pantothenic acid, cysteamine), or inhibitors efficacy. The selected studies were critically reviewed and summarized to extract key pathways, inhibitor profiles and molecular docking analyses synthesized.

Results

VNN1 hydrolyzes pantetheine to generate metabolites essential for CoA synthesis and glutathione redox balance. Its upregulation is closely associated with the pathogenesis of acute and chronic inflammatory diseases and certain cancers, often serving as a biomarker for disease severity. Inhibiting VNN1, either genetically or pharmacologically with compounds like RR6, OMP-7, or natural products such as oleuropein, demonstrates significant anti-inflammatory and antioxidant effects in preclinical models.

Conclusions

VNN1 represents a promising therapeutic target for modulating oxidative stress and immunometabolism in various diseases. Future research should develop disease-specific inhibitors, clarify tissue-specific mechanisms, and conduct clinical trials for translation.

免疫代谢稳态和氧化还原平衡之间复杂的平衡对维持健康至关重要,其失调与广泛的疾病有关。血管非炎性分子-1 (VNN1)是一种新兴的泛素酶,处于炎症和代谢的十字路口,但综合其组织和疾病特异性作用并系统评估其作为治疗靶点的潜力的综合综述仍然缺乏。方法:系统检索国内外有关VNN1的相关文献。搜索包括PubMed等数据库,使用与VNN1的结构和功能、其代谢物(泛酸、半胱胺)的疾病作用或抑制剂功效相关的关键词。对选定的研究进行了严格的回顾和总结,以提取关键途径,合成抑制剂谱和分子对接分析。结果:VNN1水解泛氨酸产生辅酶a合成和谷胱甘肽氧化还原平衡所必需的代谢物。它的上调与急慢性炎症性疾病和某些癌症的发病机制密切相关,通常作为疾病严重程度的生物标志物。在临床前模型中,通过基因或药理学方法,用化合物如RR6、OMP-7或天然产物如橄榄苷抑制VNN1,显示出显著的抗炎和抗氧化作用。结论:VNN1是调节多种疾病的氧化应激和免疫代谢的有希望的治疗靶点。未来的研究应开发疾病特异性抑制剂,明确组织特异性机制,并进行临床试验。
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引用次数: 0
Epidemiology and Clinical Features of Respiratory Viruses in Hospitalized Iranian Children During the COVID-19 Pandemic COVID-19大流行期间住院伊朗儿童呼吸道病毒的流行病学和临床特征
IF 2.7 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-29 DOI: 10.1002/iid3.70275
Ali Nateghi, Morvarid Hamrahjoo, Mohammad Yasaghi, Mahnaz Ramzali, Saeed Samadizadeh, Fatemeh Fotouhi, Vahid Salimi, Lobat Shahkar, Britt Nakstad, Alireza Tahamtan

Background

Acute respiratory infections (ARIs) are a significant global health concern, especially in children under five, causing approximately 4.3 million annual deaths. ARIs are mainly caused by respiratory viruses. The coronavirus disease 2019 (COVID-19) has altered the circulation of respiratory viruses. This study investigates the epidemiology and clinical features of respiratory viruses in hospitalized children during the COVID-19 pandemic in Gorgan, Iran.

Methods

A total of 264 nasopharyngeal swab samples were collected from hospitalized children between October 2021 to March 2022 at Taleghani Children's Hospital, Gorgan, Iran. The frequency of various respiratory viruses, including human parainfluenza viruses (HPIV1-4), influenza viruses A and B (FLU-A, B), human metapneumovirus (HMPV), human rhinovirus (HRV), respiratory syncytial virus (RSV), and severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2) was detected using a SYBR green-based real-time PCR assay.

Results

Out of the 264 hospitalized children, 88.2% (233) tested positive for at least one respiratory virus, with 60.2% (159) showing co-infections and 28% (74) having single infections. The most frequently detected were HRV (56.4%), HMPV (53%), and RSV (18.2%). The proportions of HPIV-1, HPIV-2, HPIV-3, HPIV-4, FLU-A, FLU-B, and SARS-CoV-2 were 8.7%, 12.9%, 8%, 7.6%, 1.9%, 0%, and 15.2%, respectively. There was a clear association between specific viruses and some clinical symptoms, such as RSV with pneumonia, and HPIV-1 with cyanosis. Co-infections were linked to severe outcomes, including pneumonia and seizures. Among all 264 patients, 5 died, and 3 of them had underlying diseases. All fatal cases tested positive for at least one virus, with HMPV being the most frequently detected.

Conclusions

This study highlights the considerable impact of ARIs among children under five in Golestan Province, Iran, during the COVID-19 pandemic. The findings underscore the importance of early detection and ongoing surveillance, particularly in high-risk pediatric populations and across diverse geographic areas.

背景:急性呼吸道感染(ARIs)是一个重大的全球健康问题,特别是在五岁以下儿童中,每年造成约430万人死亡。急性呼吸道感染主要由呼吸道病毒引起。2019冠状病毒病(COVID-19)改变了呼吸道病毒的循环。本研究调查了伊朗戈尔根市COVID-19大流行期间住院儿童呼吸道病毒的流行病学和临床特征。方法:从2021年10月至2022年3月在伊朗戈尔根的Taleghani儿童医院住院的儿童中采集鼻咽拭子样本264份。采用SYBR绿色实时荧光定量PCR法检测各种呼吸道病毒的频率,包括人副流感病毒(HPIV1-4)、流感病毒A和流感病毒B (FLU-A, B)、人偏肺病毒(HMPV)、人鼻病毒(HRV)、呼吸道合胞病毒(RSV)和严重急性呼吸综合征相关冠状病毒2 (SARS-CoV-2)。结果:在264名住院儿童中,88.2%(233名)至少对一种呼吸道病毒检测呈阳性,其中60.2%(159名)为合并感染,28%(74名)为单一感染。最常见的是HRV(56.4%)、HMPV(53%)和RSV(18.2%)。HPIV-1、HPIV-2、HPIV-3、HPIV-4、流感- a、流感- b和SARS-CoV-2的比例分别为8.7%、12.9%、8%、7.6%、1.9%、0%和15.2%。特定病毒与某些临床症状之间存在明确的关联,例如RSV与肺炎,HPIV-1与紫绀。合并感染与严重后果有关,包括肺炎和癫痫发作。264例患者中5例死亡,3例有基础疾病。所有死亡病例至少对一种病毒检测呈阳性,其中HMPV是最常检测到的。结论:本研究强调了在2019冠状病毒病大流行期间,急性呼吸道感染对伊朗戈列斯坦省五岁以下儿童的重大影响。研究结果强调了早期发现和持续监测的重要性,特别是在高危儿科人群和不同地理区域。
{"title":"Epidemiology and Clinical Features of Respiratory Viruses in Hospitalized Iranian Children During the COVID-19 Pandemic","authors":"Ali Nateghi,&nbsp;Morvarid Hamrahjoo,&nbsp;Mohammad Yasaghi,&nbsp;Mahnaz Ramzali,&nbsp;Saeed Samadizadeh,&nbsp;Fatemeh Fotouhi,&nbsp;Vahid Salimi,&nbsp;Lobat Shahkar,&nbsp;Britt Nakstad,&nbsp;Alireza Tahamtan","doi":"10.1002/iid3.70275","DOIUrl":"10.1002/iid3.70275","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Acute respiratory infections (ARIs) are a significant global health concern, especially in children under five, causing approximately 4.3 million annual deaths. ARIs are mainly caused by respiratory viruses. The coronavirus disease 2019 (COVID-19) has altered the circulation of respiratory viruses. This study investigates the epidemiology and clinical features of respiratory viruses in hospitalized children during the COVID-19 pandemic in Gorgan, Iran.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 264 nasopharyngeal swab samples were collected from hospitalized children between October 2021 to March 2022 at Taleghani Children's Hospital, Gorgan, Iran. The frequency of various respiratory viruses, including human parainfluenza viruses (HPIV1-4), influenza viruses A and B (FLU-A, B), human metapneumovirus (HMPV), human rhinovirus (HRV), respiratory syncytial virus (RSV), and severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2) was detected using a SYBR green-based real-time PCR assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Out of the 264 hospitalized children, 88.2% (233) tested positive for at least one respiratory virus, with 60.2% (159) showing co-infections and 28% (74) having single infections. The most frequently detected were HRV (56.4%), HMPV (53%), and RSV (18.2%). The proportions of HPIV-1, HPIV-2, HPIV-3, HPIV-4, FLU-A, FLU-B, and SARS-CoV-2 were 8.7%, 12.9%, 8%, 7.6%, 1.9%, 0%, and 15.2%, respectively. There was a clear association between specific viruses and some clinical symptoms, such as RSV with pneumonia, and HPIV-1 with cyanosis. Co-infections were linked to severe outcomes, including pneumonia and seizures. Among all 264 patients, 5 died, and 3 of them had underlying diseases. All fatal cases tested positive for at least one virus, with HMPV being the most frequently detected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study highlights the considerable impact of ARIs among children under five in Golestan Province, Iran, during the COVID-19 pandemic. The findings underscore the importance of early detection and ongoing surveillance, particularly in high-risk pediatric populations and across diverse geographic areas.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
RETRACTION: PRMT5 Participates in B Cell Overactivation in Patients With Primary Sjogren's Syndrome (pSS) Through RSAD2-Mediated NF-κB Signaling 撤回:PRMT5通过rsad2介导的NF-κB信号参与原发性干燥综合征(pSS)患者B细胞过度激活。
IF 2.7 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-29 DOI: 10.1002/iid3.70269

RETRACTION: H. Zhu, J. Zheng, Y. Zhou, T. Wu, and T. Zhu, “PRMT5 Participates in B Cell Overactivation in Patients With Primary Sjogren's Syndrome (pSS) Through RSAD2-Mediated NF-κB Signaling,” Immunity, Inflammation and Disease 11, no. 12 (2023): e1102, https://doi.org/10.1002/iid3.1102.

The above article, published online on 13 December 2023 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Marc Veldhoen; and John Wiley & Sons, Ltd. The retraction has been agreed upon due to the identification of duplication of the p-p65 western blot bands between Figures 4C and 6E. The duplication consists of rotated versions of the same bands, which were used to represent different scientific conditions. Discrepancies were also noted in the participant profile and funding information. The study included an unusually high proportion of male participants for a condition known to predominantly affect women. Additionally, the funding statement lacked institutional attribution and appeared misaligned with the study's focus. The authors did not respond to invitations to comment on the concerns or provide supporting data. As a result, the editors consider the results and conclusions to be compromised.

引用本文:朱竑,郑军,周艳,吴涛,朱涛,“PRMT5通过rsad2介导的NF-κB信号参与原发性干燥综合征(pSS)患者B细胞过度激活”,《中华免疫杂志》,第11期,no. 11。12 (2023): e1102, https://doi.org/10.1002/iid3.1102。上述文章于2023年12月13日在线发表在Wiley在线图书馆(wileyonlinelibrary.com)上,经作者同意撤回;杂志主编Marc Veldhoen;和约翰威利父子有限公司。由于在图4C和6E之间发现了p-p65 western blot条带的重复,因此同意撤回。这种复制是由同一条带的旋转版本组成的,它们被用来代表不同的科学条件。在参与者简介和供资资料中也注意到差异。该研究包括了异常高比例的男性参与者,他们的疾病已知主要影响女性。此外,资助声明缺乏机构归属,似乎与研究的重点不一致。作者没有回应就这些担忧发表评论或提供支持数据的邀请。因此,编辑们认为结果和结论受到了损害。
{"title":"RETRACTION: PRMT5 Participates in B Cell Overactivation in Patients With Primary Sjogren's Syndrome (pSS) Through RSAD2-Mediated NF-κB Signaling","authors":"","doi":"10.1002/iid3.70269","DOIUrl":"10.1002/iid3.70269","url":null,"abstract":"<p><b>RETRACTION:</b> H. Zhu, J. Zheng, Y. Zhou, T. Wu, and T. Zhu, “PRMT5 Participates in B Cell Overactivation in Patients With Primary Sjogren's Syndrome (pSS) Through RSAD2-Mediated NF-κB Signaling,” <i>Immunity, Inflammation and Disease</i> 11, no. 12 (2023): e1102, https://doi.org/10.1002/iid3.1102.</p><p>The above article, published online on 13 December 2023 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Marc Veldhoen; and John Wiley &amp; Sons, Ltd. The retraction has been agreed upon due to the identification of duplication of the p-p65 western blot bands between Figures 4C and 6E. The duplication consists of rotated versions of the same bands, which were used to represent different scientific conditions. Discrepancies were also noted in the participant profile and funding information. The study included an unusually high proportion of male participants for a condition known to predominantly affect women. Additionally, the funding statement lacked institutional attribution and appeared misaligned with the study's focus. The authors did not respond to invitations to comment on the concerns or provide supporting data. As a result, the editors consider the results and conclusions to be compromised.</p>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nucleotide-Binding Oligomerization Domain 2 in Signaling, Immunity, and Mycobacterial Infection 信号、免疫和分枝杆菌感染中的核苷酸结合寡聚化结构域2。
IF 2.7 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-28 DOI: 10.1002/iid3.70272
Yi Wang, Zihao Mi, Hong Liu, Furen Zhang

Introduction

Nucleotide-binding oligomerization domain 2 (NOD2) functions primarily as a cytoplasmic pattern recognition receptor (PRR) that detects muramyl dipeptide (MDP), a conserved bacterial cell wall component, thereby playing a pivotal role in pathogen surveillance. However, emerging evidence reveals that NOD2 exerts broad immunomodulatory effects beyond its canonical role as a PRR, though its effects can be contradictory, depending on genetic background, immunological microenvironment, and disease context. In this review, we integrate recent advances in understanding NOD2's functional plasticity and provide novel insights into its regulatory mechanisms in immune responses and mycobacterial infections.

Methods

A literature search was conducted using the PubMed database with keywords including NOD2, signaling pathways, immune homeostasis, autophagy, trained immunity, and mycobacterial infection. Relevant information was extracted from the retrieved research articles and reviews and summarized.

Results

We delineated the MDP-dependent and -independent mechanisms of NOD2 activation and their downstream signaling cascades. We also elaborated on the classical immune responses orchestrated by NOD2, and its remarkably multifaceted noncanonical roles in regulating immune homeostasis by modulating autophagy, acting synergistically with toll-like receptor pathways to fine-tune inflammation, and balancing trained immunity and immune tolerance. Furthermore, we examined the multifaceted immunoregulatory functions of NOD2 in host defense against mycobacterial infections.

Conclusions

We propose that further research is required to clarify the various roles of NOD2 across diverse genetic backgrounds, microenvironmental contexts, and disease paradigms. Such studies will provide critical mechanistic insights to inform the development of precision-based therapeutic strategies targeting NOD2.

摘要:核苷酸结合寡聚化结构域2 (NOD2)主要作为细胞质模式识别受体(PRR),检测细菌细胞壁保守成分muramyl二肽(MDP),从而在病原体监测中发挥关键作用。然而,新出现的证据表明,NOD2具有广泛的免疫调节作用,超出了其作为PRR的典型作用,尽管其作用可能是相互矛盾的,这取决于遗传背景、免疫微环境和疾病背景。在这篇综述中,我们整合了NOD2功能可塑性的最新研究进展,并对其在免疫应答和分枝杆菌感染中的调节机制提供了新的见解。方法:使用PubMed数据库进行文献检索,关键词包括NOD2、信号通路、免疫稳态、自噬、训练免疫和分枝杆菌感染。从检索到的研究文章和综述中提取相关信息并进行总结。结果:我们描述了NOD2激活的mdp依赖性和非依赖性机制及其下游信号级联。我们还详细阐述了NOD2介导的经典免疫反应,以及它在调节自噬、与toll样受体通路协同调节炎症、平衡训练免疫和免疫耐受等免疫稳态中的显著多层面非规范作用。此外,我们还研究了NOD2在宿主防御分枝杆菌感染中的多方面免疫调节功能。结论:我们认为需要进一步的研究来阐明NOD2在不同遗传背景、微环境背景和疾病范式中的各种作用。这些研究将提供关键的机制见解,为开发针对NOD2的精确治疗策略提供信息。
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引用次数: 0
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Immunity, Inflammation and Disease
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