Shifei Sun, Zhiyong Lu, Qing Yang, Wenchang Xu, Fengjun Zhang, Gongchang Yu, Bin Shi
{"title":"Predictive Value of the Systemic Immune-Inflammation Index for the Clinical Efficacy of Acupuncture and Exercise Rehabilitation in Knee Osteoarthritis: A Retrospective Study.","authors":"Shifei Sun, Zhiyong Lu, Qing Yang, Wenchang Xu, Fengjun Zhang, Gongchang Yu, Bin Shi","doi":"10.1002/iid3.70430","DOIUrl":"10.1002/iid3.70430","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the predictive value of the systemic immune-inflammation index (SII) for clinical efficacy of acupuncture combined with exercise rehabilitation in patients with knee osteoarthritis (KOA).</p><p><strong>Methods: </strong>In this retrospective observational study, 151 patients with radiographically confirmed Kellgren-Lawrence Grade II or III KOA who completed an 8-week standardized protocol of acupuncture and exercise rehabilitation were enrolled. Clinical efficacy was defined as the attainment of minimal clinically important improvement (MCII) in both the 11-point Numeric Rating Scale (NRS) for pain (≥ 2-point reduction) and the 68-point WOMAC function subscale (≥ 6-point improvement, Likert version 3.1). Baseline demographic, clinical, and hematological data were collected, and SII was subsequently calculated from baseline hematological parameters. Uni- and multivariate logistic regression analyses were used to identify independent predictors of treatment response. Receiver operating characteristic (ROC) curves were constructed to assess the discriminative ability of SII, body mass index (BMI), and lymphocyte count, individually and in combination.</p><p><strong>Results: </strong>Of the 151 patients, 73 were classified as responders and 78 as nonresponders. Baseline BMI and SII were significantly lower, while lymphocyte count was higher in the effective group (all p < 0.001). Multivariate logistic regression identified BMI (OR = 0.596, 95% CI: 0.472-0.753), lymphocyte count (OR = 34.597, 95% CI: 3.234-370.131), and SII (OR = 0.912, 95% CI: 0.873-0.953) as independent predictors of treatment response. ROC analysis showed that SII demonstrated only moderate predictive power (AUC = 0.749, 95% CI: 0.670-0.828), with improved but still moderate accuracy when combined with BMI and lymphocyte count (AUC = 0.858, 95% CI: 0.799-0.917).</p><p><strong>Conclusion: </strong>Although SII is an independent and accessible biomarker for predicting clinical efficacy, its discriminative ability is moderate. A combined model incorporating SII, BMI, and lymphocyte count may provide better, though not strong, predictive performance and could support clinical decision-making and individualized treatment planning. However, the retrospective single-center design may introduce selection bias and limit generalizability. Residual confounding from unmeasured variables cannot be excluded, and the absence of longitudinal SII measurements limits evaluation of temporal changes. Future multicenter prospective studies are warranted to validate these findings.</p>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 5","pages":"e70430"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836957","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}
{"title":"Impact of Early COVID-19 Antiviral Therapy on the Incidence of Uveitis: A Retrospective Cohort Study Using the TriNetX Database.","authors":"Hou-Ting Kuo, Alan Y Hsu, De-Yi Liu, Bing-Qi Wu, James Cheng-Chung Wei, Ning-Yi Hsia, Yi-Ching Shao, Chun-Ting Lai, Chun-Chi Chiang, Chun-Ju Lin, Huan-Sheng Chen, Yu-Hsun Wang, Hsin Tseng, Ho-Che Hsu, Yi-Yu Tsai","doi":"10.1002/iid3.70455","DOIUrl":"10.1002/iid3.70455","url":null,"abstract":"<p><strong>Objective: </strong>To assess whether antivirals are associated with a reduced incidence of uveitis following COVID-19.</p><p><strong>Methods: </strong>We conducted a multi-institutional, population-based retrospective cohort study of adults (≥ 18 years) diagnosed with COVID-19 between 2022 and 2024. Patients who received antiviral agents (Paxlovid, Molnupiravir, or Remdesivir) within 5 days of diagnosis were matched 1:1 with untreated controls using propensity score matching. Patients with pre-existing uveitis, early-onset uveitis within 5 days of the index date, or underlying systemic inflammatory or infectious diseases were excluded. The primary outcome was new-onset uveitis, with hazard ratios (HRs) calculated across follow-up intervals.</p><p><strong>Results: </strong>After matching, 438,455 patients were included in both the antiviral and non-antiviral groups. Antiviral therapy was associated with a significantly lower risk of uveitis at 3 months (HR = 0.62, 95% CI: 0.45-0.87), 6 months (HR = 0.68, 95% CI: 0.54-0.87), 1 year (HR = 0.76, 95% CI: 0.64-0.91), 3 years (HR = 0.80, 95% CI: 0.70-0.92), and all duration (HR = 0.81, 95% CI: 0.71-0.93). Subgroup analysis revealed consistent benefit across all age groups, with females experiencing greater protection than males. Significant reductions in uveitis risk were observed among patients with diabetes (HR = 0.68, 95% CI: 0.52-0.89), hyperlipidemia (HR = 0.78, 95% CI: 0.65-0.95), and heart failure (HR = 0.52, 95% CI: 0.30-0.90). Among the antivirals, Paxlovid was associated with a significant risk reduction (HR = 0.83, 95% CI: 0.71-0.96), whereas Molnupiravir and Remdesivir showed no statistically significant effect. CEV classification did not show significant improvement. Besides, the risk reduction was evident regardless of prior COVID-19 vaccination status.</p><p><strong>Conclusions: </strong>Early antiviral treatment for COVID-19 such as Paxlovid, is associated with a reduced risk of uveitis. These findings suggest that, in addition to mitigating systemic disease progression, antiviral therapy may confer ocular protective effects, which could be especially meaningful for high-risk populations.</p>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 5","pages":"e70455"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836686","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}
Nima Javanmehr, Asal Moazzami Ashtyani, Robabehbeygom Ghafelehbashi, Fateme Mousavi, Hossein Teimouri
{"title":"Nanotechnology Meets Immunotherapy: Crosstalks Against Cancer.","authors":"Nima Javanmehr, Asal Moazzami Ashtyani, Robabehbeygom Ghafelehbashi, Fateme Mousavi, Hossein Teimouri","doi":"10.1002/iid3.70437","DOIUrl":"10.1002/iid3.70437","url":null,"abstract":"<p><strong>Background: </strong>The convergence of nanotechnology and immunotherapy has ushered in a transformative era in cancer treatment, offering new strategies to overcome pharmacokinetic limitations and immune evasion associated with conventional therapies. While immunotherapy, spanning checkpoint inhibitors, adoptive cell transfer, and cancer vaccines, has revolutionized oncology, its efficacy remains constrained by the immunosuppressive tumor microenvironment (TME), off-target toxicity, and poor biodistribution of therapeutic agents.</p><p><strong>Objective: </strong>This review elucidates how engineered nanoparticles (NPs) are redefining immune-oncology by enabling the precise delivery of immunomodulators, antigens, and genetic payloads to target cells, while reprogramming the TME to convert \"cold\" tumors into immunogenic \"hot\" landscapes.</p><p><strong>Methods: </strong>A literature search was conducted using PubMed, Scopus, and Google Scholar. The review was performed in a narrative and non-systematic manner, focusing on studies addressing nanotechnology-enhanced cancer immunotherapy.</p><p><strong>Results: </strong>We dissect the physicochemical and functional versatility of NPs, emphasizing size-, charge-, and ligand-dependent strategies to enhance lymph node targeting, APC activation, and sustained cargo release. Innovations in metallic, lipid-based, and biomimetic NPs are highlighted, including gold and lipid-based NPs for enhanced immune responses. Furthermore, we explore combinatorial approaches, such as NP-mediated co-delivery of checkpoint inhibitors and chemotherapeutics, which amplify cytotoxic T-cell responses and mitigate systemic toxicity. Clinical advancements, including Nab-Paclitaxel and mRNA-loaded lipid NPs, underscore the translational potential of these platforms, with trials demonstrating improved survival and manageable adverse profiles.</p><p><strong>Conclusion: </strong>However, challenges persist in optimizing targeting precision, scalability, and long-term safety. Integrating breakthroughs in material science, immunology, and bioengineering, this review charts a roadmap for next-generation nano-immunotherapies, advocating patient-specific designs and multimodal regimens. As the field strides toward clinical maturity, nanotechnology is poised to unlock the full potential of immunotherapy, paving the way for adaptive, immune-guided, and potentially curative cancer therapies.</p>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 5","pages":"e70437"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13150694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837013","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}
{"title":"Peripheral Blood Biomarkers Predict Outcomes in Advanced Cancers Treated With Anti-PD-1 Therapy.","authors":"Chunxia Feng, Ping Li, Qianhui Gu, Minbin Chen, Jinhua Gu","doi":"10.1002/iid3.70402","DOIUrl":"10.1002/iid3.70402","url":null,"abstract":"<p><strong>Objective: </strong>PD-1 inhibitors are increasingly used in advanced cancers, but reliable biomarkers for predicting treatment response remain limited.</p><p><strong>Methods: </strong>In this retrospective cohort study, we analyzed 335 patients with stage IV cancers treated with anti-PD-1 therapy (The First People's Hospital of Kunshan, 2019-2025). A predictive model integrating peripheral blood markers and clinical factors was developed using logistic and Cox regression.</p><p><strong>Results: </strong>Histologic subtype, dNLR ≤ 3.18, AMC ≤ 0.48, and IL-6 ≤ 12.35 were independent prognostic factors for OS and PFS (multivariate HRs reported). Patients with ≥ 3 favorable factors had significantly better outcomes. The model showed high accuracy for 1-year survival prediction (AUC = 0.83) but limited performance beyond 3 years.</p><p><strong>Conclusion: </strong>This study proposes a clinically feasible biomarker-based tool to stratify PD-1 inhibitor responders, though further validation in prospective cohorts is needed.</p>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 5","pages":"e70402"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837021","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}
{"title":"Expression of Programmed Death-Ligand 1 in Cervical Cancer: Correlation With Histologic Subtypes and Clinicopathological Features.","authors":"Zahra Vahedpoor, Amirhasan Matini, Habibollah Rahimi, Majid Lotfinia, Hossein Motedayyen, Leyla Sadat Hejazi","doi":"10.1002/iid3.70464","DOIUrl":"10.1002/iid3.70464","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer remains a significant global health challenge, with squamous cell carcinoma (SCC) and adenocarcinoma representing its predominant histologic types. Programmed death-ligand 1 (PD-L1) expression in cervical cancer has been implicated in tumor immune evasion, yet its prognostic significance remains unclear. This study aimed to evaluate PD-L1 expression in cervical cancer and its association with clinicopathological features and patient survival.</p><p><strong>Methods: </strong>This study included formalin-fixed, paraffin-embedded tissue samples from forty-seven patients with cervical cancer. PD-L1 expression was assessed by immunohistochemistry (IHC) and correlated with clinical data, HPV status (determined by p16 IHC and HPV DNA PCR/genotyping), and 2-year survival outcomes. Statistical analyses included Fisher's exact test and Kaplan-Meier survival analysis.</p><p><strong>Results: </strong>PD-L1 was expressed in 61.2% of cases, predominantly in keratinizing SCC (p = 0.006) and tumors with diffuse HPV positivity (p < 0.001). PD-L1 expression significantly correlated with advanced FIGO stage (p = 0.03) but not with age, vascular invasion, and 2-year survival. No significant survival difference was observed between PD-L1 positive and negative groups.</p><p><strong>Conclusions: </strong>PD-L1 is frequently expressed in cervical carcinoma, especially keratinizing SCC and HPV-diffuse tumors, but its expression was not associated with 2-year survival. The heterogeneous expression and complex tumor-immune interactions suggest that PD-L1 alone is insufficient as a prognostic biomarker. Future research integrating additional immune and molecular markers is needed to improve prognostication and therapeutic stratification.</p>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 5","pages":"e70464"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837431","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}
{"title":"LL-37: Biological Mechanisms and Emerging Therapeutic Applications in Intestinal Disease.","authors":"Qichao Liu, Peng Xu, Cheng Zhang","doi":"10.1002/iid3.70451","DOIUrl":"10.1002/iid3.70451","url":null,"abstract":"<p><p>Human cathelicidin peptide LL-37 is encoded by the CAMP gene and plays a key role in innate immunity. It maintains intestinal homeostasis through antibacterial, immunomodulation, and tissue repair functions. This paper reviews the multiple functions of LL-37 in the intestinal-immune axis and its contribution to intestinal immune homeostasis. A large amount of evidence shows that the biological effect of LL-37 is highly dependent on the environmental background, and its effects vary with peptide concentration, receptor binding status, disease stage, and local microenvironment. This article reviews the latest findings of the dual role of LL-37 in inflammatory bowel disease (IBD) and colorectal cancer (CRC), and focuses on the conditional mechanism of the transformation of its activity from protective to pathogenic. We also discuss the interaction between LL-37 and intestinal microbiota, focusing on how microbial signals and host peptides can coordinate to regulate mucosal immunity. At the same time, this article examines the key obstacles to the therapeutic application of LL-37 and its clinical promotion: cytotoxicity, rapid degradation by proteases, and drug resistance. We have further explored new strategies to overcome these challenges in the near future, including peptide engineering, nanocarrier delivery systems, and combined therapy. These findings together position LL-37 at the intersection of intestinal immunity and microbial ecology, providing a theoretical basis for its therapeutic application in IBD, CRC and infectious colitis.</p>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 5","pages":"e70451"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13150692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836954","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}
Xinyan Zhang, Huan Li, Xueqing Zhou, Shangwen Qi, Songwei Li
{"title":"Trends and Research Hotspots in Biomarkers of Sjögren's Syndrome Over the Past Two Decades: A Data-Driven Atlas Analysis.","authors":"Xinyan Zhang, Huan Li, Xueqing Zhou, Shangwen Qi, Songwei Li","doi":"10.1002/iid3.70462","DOIUrl":"10.1002/iid3.70462","url":null,"abstract":"<p><strong>Background: </strong>Sjögren's syndrome (SS) is a chronic, systemic inflammatory disorder primarily characterized by dry eyes and dry mouth, often involving multiple organ systems. The disease's heterogeneous clinical presentation and the absence of non-invasive, specific biomarkers complicate its diagnosis and prognostic assessment.</p><p><strong>Methods: </strong>Literature was sourced from the Web of Science Core Collection, and a bibliometric network was constructed using VOSviewer, CiteSpace, and Bibliometrix. This analysis covered countries/regions, institutions, journals, authors, citations, and keywords, offering an overview of SS biomarker research and identifying future directions.</p><p><strong>Results: </strong>A total of 1118 articles on SS biomarkers were analyzed. Publication trends fluctuated over the years, with China and the United States leading in volume and citation frequency. The Assistance Publique-Hôpitaux de Paris was the most prolific institution. Among researchers, Xavier Mariette dominated the field, with leading positions in volume of publications, h-index, and total citations. Annals of the Rheumatic Diseases emerged as the most influential journal. Over the past two decades, research has expanded significantly, with emerging themes including \"DNA methylation,\" \"genes,\" \"interstitial lung disease,\" and \"data-driven,\" indicating future focus areas such as epigenetics, severe complication biomarkers, and multi-omics studies.</p><p><strong>Conclusion: </strong>This bibliometric analysis provides a comprehensive view of SS biomarker research, highlighting recent trends and future research directions, offering valuable insights for ongoing studies.</p>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 5","pages":"e70462"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837123","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}
Robert J Samuels, Nell G Bond, Ibrahim Sumah, Donald S Grant, Mohamed S Kamara, Lydia Bazzano, Camilo Fernandez, Rodrigo Borrega, Sruti Chandra, Celia R Glezer, John S Schieffelin, Troy D Moon
{"title":"Widespread SARS-CoV-2 Transmission Despite Limited Reported Cases and Clinical Disease: Exploring the Role of Pre-Existing Humoral Immunity to SARS-CoV-2 in Eastern Sierra Leone.","authors":"Robert J Samuels, Nell G Bond, Ibrahim Sumah, Donald S Grant, Mohamed S Kamara, Lydia Bazzano, Camilo Fernandez, Rodrigo Borrega, Sruti Chandra, Celia R Glezer, John S Schieffelin, Troy D Moon","doi":"10.1002/iid3.70463","DOIUrl":"10.1002/iid3.70463","url":null,"abstract":"<p><strong>Background: </strong>Since December 2019, SARS-CoV-2 has infected over 700 million people and caused > 7 million deaths. While much of the global north was severely affected, sub-Saharan Africa was relatively spared. Possible reasons include a younger population, fewer comorbidities, and pre-existing immunity. Here, we expand on previous work through a cohort of 306 subjects, with samples drawn pre-pandemic, intra-pandemic, and post-vaccination.</p><p><strong>Methods: </strong>We assessed antibody reactivity to seasonal coronaviruses, emerging coronaviruses, and SARS-CoV-2 spike (S), nucleoprotein (N), and receptor binding domain (RBD) proteins in a longitudinal cohort. Antibody neutralization was measured using a pseudovirus neutralization assay.</p><p><strong>Results: </strong>Our data show that 16%-20% of pre-pandemic samples had reactivity to SARS-CoV-2 N protein. Further, we noted relatively high reactivity to SARS-CoV-2 RBD (~31%), and low, but notable, seropositivity to SARS-CoV-2 S protein (3.3%-3.4%). We additionally found a significant jump in seropositivity to all SARS-CoV-2 proteins by March 2022 (intra-pandemic), and high levels of neutralization in the intra-pandemic samples compared to pre-pandemic samples. A boosting effect on SARS-CoV-2 Spike was observed after vaccination.</p><p><strong>Conclusions: </strong>We report widespread circulation of SARS-CoV-2 in eastern Sierra Leone by March 2022 despite low national reporting. Furthermore, we provide evidence of pre-existing humoral immunity to SARS-CoV-2 as compared to US controls. This may have resulted in less severe disease, less COVID-19 testing and the apparent lack of clinical cases. Finally, we show boosting of SARS-CoV-2 Spike following vaccination. Studies comparing HLA type between symptomatic and asymptomatic cases are being planned. Studies to better characterize cellular immunity from pre-pandemic timepoints should also be prioritized.</p>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 5","pages":"e70463"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837115","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}
Sheng Zhao, Yuejiao Li, Wenchuan Li, Lan Dong, Rong Lian, Qingqing Luo, Xingji Lian, Jianbo Li, Feng He
{"title":"Characterization of NLRP3 Inflammasome-Associated Hub Genes in the Progression of Diabetic Nephropathy","authors":"Sheng Zhao, Yuejiao Li, Wenchuan Li, Lan Dong, Rong Lian, Qingqing Luo, Xingji Lian, Jianbo Li, Feng He","doi":"10.1002/iid3.70424","DOIUrl":"https://doi.org/10.1002/iid3.70424","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diabetic nephropathy (DN) is widely recognized as the primary cause of end-stage renal disease. However, the underlying mechanisms and pathogenesis of DN remain incompletely understood. Exploring novel biomarkers aiding in tracking the progression of DN has important clinical implications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Human renal transcriptomic datasets (GSE142025 and GSE96804) from the Gene Expression Omnibus (GEO) were analyzed. Differentially expressed genes (DEGs) were identified using a staged analysis, which involved sequential comparisons between normal controls and early-stage DN, as well as between early DN (eDN) and advanced DN (aDN). Enrichment analysis of DEGs was performed using R software. WGCNA was utilized to construct gene co-expression networks and to identify the key genes. Then, Venn diagrams were generated using DEGs and key genes from both datasets to determine the final hub genes. ROC curves were then used to assess the diagnostic accuracy of hub genes for DN disease progression. Finally, we cross-validated the hub genes using the clinical kidney specimens.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After analyzing the datasets, we identified 22 and 43 hub genes using the WGCNA and DEGs at the eDN and aDN stages. Further investigation of the literature on the hub genes led to the discovery of their association with the activity of NLRP3 inflammasome, including <i>ZFP36</i>, <i>CLEC2D</i>, and <i>HCK</i>, which were identified as NLRP3 inflammasome-associated hub genes (NIAHGs). We found that the AUC of all the NIAHGs can indicate their potential diagnostic value. Then, we validated the expression levels of NIAHGs in human renal tissues, which were consistent with those in both data sets. Importantly, immunoblot analysis indicated that NIAHGs expression was associated with NLRP3 inflammasome activation. Furthermore, NLRP3 inflammasome was significantly activated, leading to the release of large amounts of IL-1β and IL-18 in eDN, further initiating the inflammatory response in the diabetic kidney.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings identify critical hub genes associated with DN progression and NLRP3 inflammasome activity, providing a theoretical basis and candidate targets for subsequent research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70424","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147668504","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}
{"title":"Safety and Efficacy of Obinutuzumab in Treating Lupus Nephritis: A Systematic Review","authors":"Zainab Arif, Hafsa Ali, Erum Siddiqui, Shorrem Naeem, Mohammed Hammad Jaber Amin","doi":"10.1002/iid3.70439","DOIUrl":"https://doi.org/10.1002/iid3.70439","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus (SLE), often leading to end-stage renal disease. Despite current immunosuppressive therapies, complete renal remission remains limited. Obinutuzumab, a type II anti-CD20 monoclonal antibody, offers enhanced B-cell depletion compared to type I antibodies and may improve renal outcomes in LN. This systematic review evaluates the efficacy and safety of obinutuzumab in treating adult patients with proliferative LN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review was registered with PROSPERO (CRD420251074418) and conducted in accordance with the PRISMA guidelines. A comprehensive search of PubMed, Cochrane, Embase, Scopus, and clinical trial registries was conducted through June 2025. Eligible studies were randomized controlled trials (RCTs) comparing obinutuzumab vs. placebo in adult patients with biopsy-confirmed active LN. Primary outcomes included complete renal response (CRR), proteinuria, and estimated glomerular filtration rate (eGFR). Secondary outcomes included immunological markers and adverse events. Data were synthesized qualitatively due to the limited available trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Two RCTs (REGENCY 2025 and NOBILITY 2022) with 396 patients met the inclusion criteria. Obinutuzumab significantly improved CRR (46.4% in REGENCY at week 76; 41% in NOBILITY at week 104) and reduced proteinuria (UPCR < 0.5 in 62% vs. 37% in controls). Improvements in eGFR, complement levels (C3 and C4), and anti-dsDNA titers were also noted. Adverse events occurred at similar rates across groups, although serious infections and infusion reactions were somewhat higher in one trial. No significant increase in mortality was observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Obinutuzumab appears to be a promising therapy for proliferative LN, offering enhanced renal response and immunological benefits. Its potential for long-term renal protection and steroid-sparing effects supports further investigation through large-scale comparative trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70439","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147668394","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}