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.
{"title":"Predictive Value of Combined CRP and INR for Intracranial Hypertension in Cerebral Venous Thrombosis","authors":"Jiahui Yan, Manli Lu, Zhichao Huang, Yingying Xu, Yongjun Cao, Jianqiang Ni, Xia Zhang","doi":"10.1002/iid3.70265","DOIUrl":"10.1002/iid3.70265","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>We aimed to develop a noninvasive model combining biomarkers and clinical features to predict IH in CVT patients, facilitating early risk stratification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>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.</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/PMC12521872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292021","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}
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%.
{"title":"Dust Mite Serodominance Profiles in Lugo","authors":"Francisco Carballada, Luis Alfredo González, Ramón Núñez, Raquel Lopez, Joaquín Martín, Nicola Giangrande, Antonio García-Dumpierrez, Javier Alcover, David Rodríguez, Ricardo Palacios","doi":"10.1002/iid3.70254","DOIUrl":"10.1002/iid3.70254","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>House dust mite allergy affects 65–130 million people worldwide. Untreated patients could develop severe allergic diseases such as atopic dermatitis and asthma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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 <i>Dermatophagoides pteronyssinus</i> 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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>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%.</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/PMC12522014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292035","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}
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.
{"title":"Revealing VNN1: An Emerging and Promising Target for Inflammation and Redox Balance","authors":"Linxi Lv, Tian Wang, Wenzhan Xie, Jialong Wei, Laixian Zhou, Xiaopei Qiu, Hui Feng, Wei Gu","doi":"10.1002/iid3.70274","DOIUrl":"10.1002/iid3.70274","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>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.</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/PMC12521874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292097","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}
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.
{"title":"Epidemiology and Clinical Features of Respiratory Viruses in Hospitalized Iranian Children During the COVID-19 Pandemic","authors":"Ali Nateghi, Morvarid Hamrahjoo, Mohammad Yasaghi, Mahnaz Ramzali, Saeed Samadizadeh, Fatemeh Fotouhi, Vahid Salimi, Lobat Shahkar, Britt Nakstad, 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}
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 & 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}
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.
{"title":"Nucleotide-Binding Oligomerization Domain 2 in Signaling, Immunity, and Mycobacterial Infection","authors":"Yi Wang, Zihao Mi, Hong Liu, Furen Zhang","doi":"10.1002/iid3.70272","DOIUrl":"10.1002/iid3.70272","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185024","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}
Kawasaki disease (KD) is a leading cause of acquired heart disease in children. Evidence suggests that microbial and nonmicrobial triggers for KD differ across geographical regions and environmental conditions. Although the precise triggers remain unidentified, KD is likely caused by microbial or environmental agents acting on genetically predisposed children.
Recent Findings
Insights into KD pathogenesis have also been derived from three well-established murine models, which highlight diverse vasculitis-inducing pathways. The diversity of microbial triggers supports the hypothesis that KD arises from immune-mediated responses rather than direct infection. Pathogen-associated molecular patterns (PAMPs), microbe-associated molecular patterns (MAMPs) and inflammatory cell death-linked damage-associated molecular patterns (DAMPs) play critical roles in KD pathogenesis. Furthermore, genetic polymorphisms associated with KD, such as ITPKC, CASP3, and FCGR2A, contribute to immune activation by promoting inflammasome activation, pyroptosis and antibody-dependent enhancement (ADE), thereby intensifying inflammation. Oxidative and nitrative stress further amplify inflammatory responses, with their interplay potentially driving KD onset. The relatively low recurrence rate of KD, despite its diverse triggers, may partly be explained by the presence of anti-DAMP antibodies. Historically, reduced exposure to infections and improved sanitation may have led to lower levels of anti-DAMP antibodies, potentially contributing to the increased incidence of KD observed over time.
Conclusion
Continued research into microbial and immune mechanisms is crucial to advance our understanding of KD pathogenesis.
{"title":"The Etiopathogenesis of Kawasaki Disease: Evolving Understanding of Diverse Triggers","authors":"Toshiro Hara, Yasunari Sakai","doi":"10.1002/iid3.70267","DOIUrl":"10.1002/iid3.70267","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Kawasaki disease (KD) is a leading cause of acquired heart disease in children. Evidence suggests that microbial and nonmicrobial triggers for KD differ across geographical regions and environmental conditions. Although the precise triggers remain unidentified, KD is likely caused by microbial or environmental agents acting on genetically predisposed children.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Recent Findings</h3>\u0000 \u0000 <p>Insights into KD pathogenesis have also been derived from three well-established murine models, which highlight diverse vasculitis-inducing pathways. The diversity of microbial triggers supports the hypothesis that KD arises from immune-mediated responses rather than direct infection. Pathogen-associated molecular patterns (PAMPs), microbe-associated molecular patterns (MAMPs) and inflammatory cell death-linked damage-associated molecular patterns (DAMPs) play critical roles in KD pathogenesis. Furthermore, genetic polymorphisms associated with KD, such as <i>ITPKC</i>, <i>CASP3</i>, and <i>FCGR2A</i>, contribute to immune activation by promoting inflammasome activation, pyroptosis and antibody-dependent enhancement (ADE), thereby intensifying inflammation. Oxidative and nitrative stress further amplify inflammatory responses, with their interplay potentially driving KD onset. The relatively low recurrence rate of KD, despite its diverse triggers, may partly be explained by the presence of anti-DAMP antibodies. Historically, reduced exposure to infections and improved sanitation may have led to lower levels of anti-DAMP antibodies, potentially contributing to the increased incidence of KD observed over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Continued research into microbial and immune mechanisms is crucial to advance our understanding of KD pathogenesis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185572","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}
Jiali Wu, Kaoyuan Zhang, Yan Liao, Chener Yang, Jingyao Ge, Chenchen Wu, Bo Yu, Weilong Zhong, Yong Shao, Xia Dou
Background
The available evidence increasingly indicates that SERPINB3/4 plays a pivotal role in the progression of inflammatory diseases and may serve as a valuable biomarker for atopic dermatitis and psoriasis. However, the expression of SERPINB3/4 in the serum of patients with moderate-to-severe prurigo nodularis (PN) remains poorly understood.
Objective
To find a promising biomarker for monitoring the severity and activity of moderate-to-severe PN patients.
Methods
A total of 41 patients with moderate-to-severe PN and 20 healthy subjects were included in the study. Enzymelinked immunosorbent assay (ELISA) was performed to determine serum SERPINB3/4 expression. Cutaneous SERPINB3/4 expression was evaluated by immunohistochemistry (IHC). Serum SERPINB3/4 levels were correlated with PN disease severity and activity scores, hematological parameters, and systemic inflammatory markers.
Results
SERPINB3/4 expression was found to be significantly increased in the serum and lesions of PN in comparison to healthy subjects. In patients with PN, the expression of serum SERPINB3/4 was significantly elevated in subjects with higher investigator global assessment (IGA) scores, while exhibiting a notable decline in patients with higher pruritus numeric rating scale (P-NRS) scores. Positive correlations were observed between serum SERPINB3/4 levels and peripheral eosinophil count, eosinophil ratio, and eosinophil-to-lymphocyte ratio (ELR) in patients with PN.
Conclusion
SERPINB3/4 expression was increased in PN sera and lesions. Serum SERPINB3/4 expression was positively correlated with PN severity and peripheral eosinophil-related parameters, suggesting its potential as a promising biomarker for PN.
{"title":"Serum SERPINB3/4 in Moderate-to-Severe Prurigo Nodularis: A Potential Biomarker for Disease Severity and Eosinophil-Related Parameters","authors":"Jiali Wu, Kaoyuan Zhang, Yan Liao, Chener Yang, Jingyao Ge, Chenchen Wu, Bo Yu, Weilong Zhong, Yong Shao, Xia Dou","doi":"10.1002/iid3.70263","DOIUrl":"10.1002/iid3.70263","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The available evidence increasingly indicates that SERPINB3/4 plays a pivotal role in the progression of inflammatory diseases and may serve as a valuable biomarker for atopic dermatitis and psoriasis. However, the expression of SERPINB3/4 in the serum of patients with moderate-to-severe prurigo nodularis (PN) remains poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To find a promising biomarker for monitoring the severity and activity of moderate-to-severe PN patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 41 patients with moderate-to-severe PN and 20 healthy subjects were included in the study. Enzymelinked immunosorbent assay (ELISA) was performed to determine serum SERPINB3/4 expression. Cutaneous SERPINB3/4 expression was evaluated by immunohistochemistry (IHC). Serum SERPINB3/4 levels were correlated with PN disease severity and activity scores, hematological parameters, and systemic inflammatory markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SERPINB3/4 expression was found to be significantly increased in the serum and lesions of PN in comparison to healthy subjects. In patients with PN, the expression of serum SERPINB3/4 was significantly elevated in subjects with higher investigator global assessment (IGA) scores, while exhibiting a notable decline in patients with higher pruritus numeric rating scale (P-NRS) scores. Positive correlations were observed between serum SERPINB3/4 levels and peripheral eosinophil count, eosinophil ratio, and eosinophil-to-lymphocyte ratio (ELR) in patients with PN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SERPINB3/4 expression was increased in PN sera and lesions. Serum SERPINB3/4 expression was positively correlated with PN severity and peripheral eosinophil-related parameters, suggesting its potential as a promising biomarker for PN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137355","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}
Xiao-Min Wang, Pu Li, Lei Hu, Xiao Zhang, Jun Wang, Cheng-Xin Zhu, Kun Lv, Da-Wei Zhang
Background
Severe fever with thrombocytopenia syndrome (SFTS) poses a serious threat to public health due to its high mortality. Low thoracic muscle mass predicts poor clinical outcomes in many diseases, but its significance in SFTS remains unclear.
Methods
This retrospective study involved 210 SFTS patients admitted to the First Affiliated Hospital of Anhui Medical University from 2020 to 2023. All subjects underwent chest computed tomography (CT) examination. Skeletal muscle index (SMI) was measured by CT images at the level of the twelfth thoracic vertebra (T12). The clinical data of patients from the survival and non-survival groups were compared, and the prognostic value of T12-SMI in SFTS patients was evaluated through least absolute shrinkage and selection operator regression and univariate and multivariate Cox regression.
Results
Patients in the non-survival group had a lower SMI. Receiver operating characteristic analysis indicated that SMI may predict adverse outcomes in patients with SFTS. Multivariate Cox regression analysis demonstrated that SMI was independently connected to negative outcomes of SFTS. T12-SMI was correlated with albumin and creatinine.
Conclusion
Low SMI is associated with adverse outcomes in patients with SFTS. SMI may serve as a reliable prognostic marker for SFTS in clinical settings.
{"title":"Low Thoracic Muscle Mass: A Novel Indicator of Poor Prognosis in Patients With Severe Fever With Thrombocytopenia Syndrome","authors":"Xiao-Min Wang, Pu Li, Lei Hu, Xiao Zhang, Jun Wang, Cheng-Xin Zhu, Kun Lv, Da-Wei Zhang","doi":"10.1002/iid3.70271","DOIUrl":"10.1002/iid3.70271","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Severe fever with thrombocytopenia syndrome (SFTS) poses a serious threat to public health due to its high mortality. Low thoracic muscle mass predicts poor clinical outcomes in many diseases, but its significance in SFTS remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study involved 210 SFTS patients admitted to the First Affiliated Hospital of Anhui Medical University from 2020 to 2023. All subjects underwent chest computed tomography (CT) examination. Skeletal muscle index (SMI) was measured by CT images at the level of the twelfth thoracic vertebra (T12). The clinical data of patients from the survival and non-survival groups were compared, and the prognostic value of T12-SMI in SFTS patients was evaluated through least absolute shrinkage and selection operator regression and univariate and multivariate Cox regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients in the non-survival group had a lower SMI. Receiver operating characteristic analysis indicated that SMI may predict adverse outcomes in patients with SFTS. Multivariate Cox regression analysis demonstrated that SMI was independently connected to negative outcomes of SFTS. T12-SMI was correlated with albumin and creatinine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Low SMI is associated with adverse outcomes in patients with SFTS. SMI may serve as a reliable prognostic marker for SFTS in clinical settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70271","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130719","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}
Influenza vaccinations are recommended for healthcare workers (HCWs). Quantification of the personal risks of vaccination compared to vaccine benefits can help guide more accurate benefit-risk assessment and cost-effectiveness analysis of inactivated influenza vaccination among HCWs. The study objective was to evaluate the quality-adjusted life day (QALD) loss due to adverse events following immunization (AEFI) among HCWs.
Methods
This study used a questionnaire survey with the EuroQol-5 dimension-5 level (EQ-5D) for HCWs to evaluate the impact of reactogenicity on QALD loss following inactivated seasonal influenza vaccination. Participants were asked to answer a questionnaire survey regarding their health status once daily from the day before vaccination until 7 days after vaccination (a total of 9 times). QALD loss was calculated as the cumulative difference between the mean EQ-5D scores following vaccination (Days 0–7) and the mean EQ-5D score before vaccination (Day −1).
Results
During the study period, 213 participants completed the surveys for 5 days or more, and 122 participants completed the surveys for all days. The mean QALD losses among the participants who completed the surveys for five or more days and those who completed the surveys on all days were 0.040 and 0.054, respectively. The mean QALD losses among those by grade (the maximal grade of any AEFIs) were 0.021 (grade 0), −0.018 (grade 1), 0.089 (grade 2), and 0.299 (grade 3), respectively.
Conclusion
We measured the magnitude of QALD loss in HCWs following inactivated influenza vaccination. These results support a more accurate health technology assessment of seasonal influenza vaccination in this population.
{"title":"Impact of Inactivated Influenza Vaccination on Health-Related Quality of Life Among Japanese Healthcare Workers","authors":"Taito Kitano, Sayaka Yoshida","doi":"10.1002/iid3.70266","DOIUrl":"10.1002/iid3.70266","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Influenza vaccinations are recommended for healthcare workers (HCWs). Quantification of the personal risks of vaccination compared to vaccine benefits can help guide more accurate benefit-risk assessment and cost-effectiveness analysis of inactivated influenza vaccination among HCWs. The study objective was to evaluate the quality-adjusted life day (QALD) loss due to adverse events following immunization (AEFI) among HCWs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study used a questionnaire survey with the EuroQol-5 dimension-5 level (EQ-5D) for HCWs to evaluate the impact of reactogenicity on QALD loss following inactivated seasonal influenza vaccination. Participants were asked to answer a questionnaire survey regarding their health status once daily from the day before vaccination until 7 days after vaccination (a total of 9 times). QALD loss was calculated as the cumulative difference between the mean EQ-5D scores following vaccination (Days 0–7) and the mean EQ-5D score before vaccination (Day −1).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During the study period, 213 participants completed the surveys for 5 days or more, and 122 participants completed the surveys for all days. The mean QALD losses among the participants who completed the surveys for five or more days and those who completed the surveys on all days were 0.040 and 0.054, respectively. The mean QALD losses among those by grade (the maximal grade of any AEFIs) were 0.021 (grade 0), −0.018 (grade 1), 0.089 (grade 2), and 0.299 (grade 3), respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We measured the magnitude of QALD loss in HCWs following inactivated influenza vaccination. These results support a more accurate health technology assessment of seasonal influenza vaccination in this population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086033","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}
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