Frontiers in Immunology最新文献

{"title":"Neutrophils negatively control IL-17A-producing γδ T cell frequencies in a contact-dependent manner under physiological conditions.","authors":"Xinhua Yu, Xiaoyang Yue, Junie D Tchudjin Magatsin, Sebastian Marwitz, Jochen Behrends, Torsten Goldmann, Joseph T Opferman, Brigitte Kasper, Frank Petersen","doi":"10.3389/fimmu.2025.1542191","DOIUrl":"10.3389/fimmu.2025.1542191","url":null,"abstract":"<p><strong>Background: </strong>In addition to serving as the primary effector cells against infections, neutrophils have been implicated in the regulation of both innate and adaptive immunity. In this study, we aimed to investigate the role of neutrophils in the regulation of the immune system under physiological conditions.</p><p><strong>Methods: </strong>The <i>in vivo</i> effect of neutrophils on the immune system was examined using neutropenic mice. The interaction between neutrophils and γδ T cells was investigated using an <i>in vitro</i> co-culture system.</p><p><strong>Findings: </strong>Unexpectedly, we observed an accumulation of γδ T cells in the cervical lymph nodes of neutropenic mice. Transcriptomic analysis revealed that these γδ T cells exhibited unique expression profiles of cell surface molecules and genes involved in defense responses. Further characterization indicated that the accumulated γδ T cells were IL-17 producing CD44⁺CD62L^-CD27^- memory cells. Additionally, <i>in vitro</i> experiments demonstrated that neutrophils could inhibit the function of IL-17A producing γδ T cells by inducing cell death in a contact-dependent manner.</p><p><strong>Conclusion: </strong>This present study demonstrates that neutrophils negatively regulate IL-17 producing γδ T cells under physiological conditions. Given that IL-17A is a critical cytokine for the recruitment of neutrophils to peripheral tissues, our study suggests that the crosstalk between neutrophils and IL-17A producing γδ T cells is a crucial mechanism for maintaining immune homeostasis under physiological conditions.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1542191"},"PeriodicalIF":5.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transitioning from Lupus Low Disease Activity State to remission in systemic lupus erythematosus: real-world evidence.","authors":"Dai Gao, Lanlan Ji, Xiaohui Zhang, Yanjie Hao, Wenhui Xie, Yong Fan, Zhuoli Zhang","doi":"10.3389/fimmu.2025.1546306","DOIUrl":"10.3389/fimmu.2025.1546306","url":null,"abstract":"<p><strong>Objectives: </strong>To identify predictors and barriers to achieving remission in systemic lupus erythematosus (SLE) patients after attaining Lupus Low Disease Activity State (LLDAS).</p><p><strong>Methods: </strong>This study included patients from the Sle to TARget (STAR) cohort who did not fulfill LLDAS at baseline. The Kaplan-Meier method was used to estimate the cumulative probabilities of remission or flare after LLDAS attainment. Univariate and multivariable Cox proportional hazards models were employed to identify predictors of time to remission. Barriers impeding remission achievement were also investigated.</p><p><strong>Results: </strong>Of 586 enrolled patients, 480 achieved LLDAS within 20.4 months (IQR 13.4-37.1). Among these, 369 patients who did not achieve remission simultaneously with LLDAS attainment and had ongoing follow-up were included in further analysis. Subsequently, 297 (80.5%) patients achieved remission, with median times to remission and flare of 12.4 and 24.4 months, respectively. Independent predictors of a shorter time to remission included older age at disease onset (HR 1.012, 95%CI=1.004-1.020, <i>P</i>=0.002), arthritis (HR 1.481, 95%CI=1.113-1.969, <i>P</i>=0.007), and gastrointestinal involvement (HR 1.994, 95%CI=1.230-3.232, <i>P</i>=0.005). Conversely, anemia (HR 0.564, 95%CI=0.428-0.743, <i>P</i><0.001) was a risk predictor. Higher disease activity defined by SLE Disease Activity Index 2000 (HR 0.691, 95%CI=0.632-0.757, <i>P</i><0.001) or the Physician's Global Assessment (HR 0.062, 95%CI=0.031-0.127, <i>P</i><0.001) and the presence of rash (HR 0.156, 95%CI=0.049-0.499, <i>P</i>=0.002), anti-dsDNA positivity (HR 0.513, 95%CI=0.403-0.654, <i>P</i><0.001), hypocomplementemia (HR 0.468, 95%CI=0.346-0.632, <i>P</i><0.001), or thrombocytopenia (HR 0.138, 95%CI=0.051-0.377, <i>P</i><0.001) at the time of LLDAS attainment also demonstrated negative associations with remission. Patients maintaining hydroxychloroquine (HR 1.662, 95%CI=1.115-2.477, <i>P</i>=0.013) or cyclophosphamide (HR 3.468, 95%CI=1.959-6.141, <i>P</i><0.001) regimens at LLDAS exhibited a shorter time to remission. Moreover, 68.7% of patients failed to achieve remission at the visit preceding remission solely due to prednisone doses of ≥5 mg/day, while other criteria impeded only 5.7-8.4% of cases.</p><p><strong>Conclusions: </strong>Achieving rapid remission after LLDAS attainment remains challenging for most SLE patients, mainly due to difficulties in reducing prednisone dosage to ≤5 mg/day.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1546306"},"PeriodicalIF":5.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircRNAs: a novel potential strategy to treat breast cancer.","authors":"Pangzhou Chen, Jinhui Zhang, Song Wu, Xiaoyu Zhang, Wen Zhou, Ziyun Guan, Hailin Tang","doi":"10.3389/fimmu.2025.1563655","DOIUrl":"10.3389/fimmu.2025.1563655","url":null,"abstract":"<p><p>Breast cancer is among the most prevalent malignant tumors worldwide, with triple-negative breast cancer (TNBC) being the most aggressive subtype and lacking effective treatment options. Circular RNAs (circRNAs) are noncoding RNAs that play crucial roles in the development of tumors, including breast cancer. This article examines the progress of research on circRNAs in breast cancer, focusing on four main areas: 1) breast cancer epidemiology, classification, and treatment; 2) the structure, discovery process, characteristics, formation, and functions of circRNAs; 3) the expression, mechanisms, clinical relevance, and recent advances in the study of circRNAs in breast cancer cells and the immune microenvironment, particularly in TNBC; and 4) the challenges and future prospects of the use of circRNAs in BC research.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1563655"},"PeriodicalIF":5.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>CXCR2P1</i> enhances the response of gastric cancer to PD-1 inhibitors through increasing the immune infiltration of tumors.","authors":"Xinchun Wu, Sen Hou, Yingjiang Ye, Zhidong Gao","doi":"10.3389/fimmu.2025.1545605","DOIUrl":"10.3389/fimmu.2025.1545605","url":null,"abstract":"<p><strong>Background: </strong>Recent years, immunotherapy has emerged as a pivotal approach in cancer treatment. However, the response of gastric cancer to immunotherapy exhibits significant heterogeneity. Therefore, the early identification of gastric cancer patients who are likely to benefit from immunotherapy and the discovery of novel therapeutic targets are of critical importance.</p><p><strong>Materials and methods: </strong>We collected data from European Nucleotide Archive (ENA) and Gene Expression Omnibus (GEO) databases. In project PRJEB25780, we performed WGCNA analysis and Lasso regression and chose <i>CXCR2P1</i> for the subsequent analysis. Then, we compared the expression difference of <i>CXCR2P1</i> among different groups. Kaplan-Meier curve was used to analyze the prognostic value of <i>CXCR2P1</i>, which was validated by project IMvigor210 and GEO datasets. ESTIMATE and CIBERSORT algorithm were used to evaluate the reshaping effect of <i>CXCR2P1</i> to immune microenvironment of tumor. Differentially expressed genes (DEG) analysis, enrichGO analysis, Gene Set Enrichment Analysis (GSEA) and co-expression analysis were used to explore the cell biological function and signaling pathway involved in <i>CXCR2P1.</i></p><p><strong>Results: </strong>WGCNA identified <i>CXCR2P1</i> as a hub gene significantly associated with immune response to PD-1 inhibitors in gastric cancer. <i>CXCR2P1</i> expression was elevated in responders and correlated with better prognosis. Functional analysis revealed its role in reshaping the tumor immune microenvironment by promoting immune cell infiltration, including M1 macrophages, activated <i>CD4</i>+ T cells, and follicular helper T cells. <i>CXCR2P1</i> enhanced antigen presentation via the MHC-II complex, influenced key immune pathways, such as Toll-like receptor signaling and T-cell activation, which led to the up-regulation of expression of PD-L1. GSEA showed <i>CXCR2P1</i> were correlated with microRNAs. Through DEG analysis and expression analysis, <i>MIR215</i> was identified as a potential direct target of <i>CXCR2P1</i>.</p><p><strong>Conclusion: </strong>High expression of CXCR2P1 is correlated with better response to PD-1 inhibitor. It reshapes the immune microenvironment by increasing immune infiltration and changing the fraction of immune cells. In tumor immune microenvironment, <i>CXCR2P1</i> can promote inflammation, enhance antigen presentation and activate the PD-1/PD-L1-related signaling pathway, which might be achieved by <i>CXCR2P1</i>-<i>MIR215</i> axis.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1545605"},"PeriodicalIF":5.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain injury, endocrine disruption, and immune dysregulation in HIV-positive men who have sex with men with late HIV diagnosis.","authors":"Yihui He, Hao Liu, Meixin Ren, Gaungqiang Sun, Yundong Ma, Miaotian Cai, Rui Wang, Lei Wang, Tong Zhang, Yang Zhang","doi":"10.3389/fimmu.2025.1436589","DOIUrl":"10.3389/fimmu.2025.1436589","url":null,"abstract":"<p><strong>Background: </strong>In the realm of public health, late human immunodeficiency virus (HIV) diagnosis remains prevalent and is associated with neuropsychiatric adverse events. However, there is limited documentation regarding the impact of late HIV diagnosis (LD) on brain integrity, neurotrophic factors, endocrine function, and immunity in HIV-positive men who have sex with men (MSM).</p><p><strong>Methods: </strong>Participants (38 LD and 34 non-LD of MSM) underwent comprehensive infectious disease and psychiatric assessments, multimodal magnetic resonance imaging (MRI) scans, neurotrophic factors, endocrine, and immunological evaluations. Immune cell levels, along with peripheral plasma concentrations of neurotrophic factors and hormones, were measured using enzyme-linked immunosorbent assays and flow cytometry, respectively. T1-weighted images along with resting-state functional MRI were applied to assess brain function and structure while also examining correlations between imaging alterations and clinical as well as peripheral blood variables. The data for this study originated from a subset of the cohort in HIV-associated neuropsychiatric disorders research.</p><p><strong>Results: </strong>Compared to participants in the non-LD group, those in the LD group showed a lower total gray matter volume (GMV), with reduced GMV primarily observed in the left supramarginal gyrus. Participants in the LD group exhibited differences in brain function with certain regions and decreased functional connectivity between these altered regions and connected structures. A two-way factorial analysis of variance examining the main effects and interactions between groups and neuropsychiatric disorders revealed significant main effects of LD on specific brain regions. Furthermore, we found that individuals in the LD group had higher levels of cortisol, a lower frequency of central memory T cells, and elevated expression levels of perforin in double-negative T cells. These imaging findings were significantly correlated with endocrine, immune, and clinical variables.</p><p><strong>Conclusion: </strong>This study suggests that LD may contribute to brain injury, endocrine disruption, and immune dysregulation in HIV-positive MSM. Consequently, there is an urgent need to develop public health strategies targeting late diagnosis, with a focus on strengthening screening and early detection for high-risk populations, as well as monitoring brain injury, endocrine, and immune functions in individuals with LD, and formulating precise, individualized intervention strategies to reduce the long-term impact of LD on the health of HIV-positive MSM.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1436589"},"PeriodicalIF":5.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Successful treatment of refractory systemic lupus erythematosus-associated immune thrombocytopenia with drug-induced liver injury with telitacicept: a case report and review.","authors":"Xuefei Li, Yao Fu, HaiQin Yin, Huiling Zhu","doi":"10.3389/fimmu.2025.1473190","DOIUrl":"10.3389/fimmu.2025.1473190","url":null,"abstract":"<p><p>Immune thrombocytopenia(ITP)is a common clinical manifestation of systemic lupus erythematosus(SLE). Drug therapy includes glucocorticoids(GCs),disease-modifying anti-rheumatic drugs (DMARDs) and biologics. Refractory thrombocytopenia can be life-threatening, and the use of effective medications plays a crucial role in disease improvement. Here, we report a case of ITP secondary to SLE. The use of dexamethasone(DEX), cyclosporine A(CsA), and hetrombopag resulted in drug-induced liver injury. Subsequently, telitacicept was chosen and successfully controlled the patient's condition. It suggests that telitacicept may be a new treatment option for refractory SLE-ITP.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1473190"},"PeriodicalIF":5.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amelioration of aging-induced muscular decline by black soybean (<i>Rhynchosia nulubilis</i>) and black rice (<i>Oryza sativa</i> L.) extracts.","authors":"Hyejeong Park, Seungmin Yu, Wooki Kim","doi":"10.3389/fimmu.2025.1554941","DOIUrl":"10.3389/fimmu.2025.1554941","url":null,"abstract":"<p><p>Aging leads to a decline in the mass and function of skeletal muscles, a condition known as sarcopenia. It was previously reported that aging-related alterations in protein degradation, chronic inflammation, and deterioration of mitochondrial metabolism affect the acceleration of muscle atrophy in the elderly. However, the detailed mechanism or substantial causes for age-related muscle loss are still lacking, yet exercise or an increment in dietary protein intake are suggested as effective approaches to mitigate muscle atrophy. This study aims to investigate the regulatory effect of black soybean (<i>Rhynchosia nulubilis</i>) and black rice (<i>Oryza sativa</i> L.) mixture extract (BBME), which are rich in protein and bioactive compounds, in 12-month-old aged mice and L6 myotubes. BBME was orally administered at 300 and 600 mg/kg/day (low and high doses) for 12 weeks, and its effects on systemic glucose homeostasis and skeletal muscle metabolism were evaluated. Consequently, BBME at a high dose marginally ameliorated muscle loss and significantly improved glucose metabolism. BBME also reduced cellular senescence markers and enhanced mitochondrial biogenesis in aged skeletal muscles. Additionally, BBME exerted insulin-like activity by promoting glucose metabolism in L6 myotubes. These findings suggest the potential of BBME as a functional food ingredient in alleviating aging-induced muscle loss by modulating mitochondrial activity and glucose metabolism.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1554941"},"PeriodicalIF":5.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is a rare <i>CXCL8</i> gene variant a new possible cause or curse factor of inflammatory bowel disease?","authors":"Marcin Gabryel, Oliwia Zakerska-Banaszak, Karolina Ladziak, Katarzyna Anna Hubert, Alina Baturo, Joanna Suszynska-Zajczyk, Magdalena Hryhorowicz, Agnieszka Dobrowolska, Marzena Skrzypczak-Zielinska","doi":"10.3389/fimmu.2025.1562618","DOIUrl":"10.3389/fimmu.2025.1562618","url":null,"abstract":"<p><strong>Introduction: </strong>The pathogenesis of inflammatory bowel diseases (IBD) involves genetic, environmental, immunological, and microbial factors; however, it remains unclear. Pro-inflammatory interleukin 8 (IL-8), encoded by the <i>CXCL8</i> gene, assumes a crucial chemotactic role in leukocyte migration.</p><p><strong>Methods: </strong>This study aimed to investigate whether an association exists between IBD and two <i>CXCL8</i> variants, namely, c.-251A>T (rs4073) and c.91G>T (rs188378669), and IL-8 concentration. We analyzed the distribution of both variants among 353 Polish IBD patients and 200 population subjects using pyrosequencing, competitive allele-specific PCR and Sanger sequencing.</p><p><strong>Results: </strong>The c.91T stop-gained allele was significantly more frequent in IBD patients (2.12%) than in controls (0.25%) (<i>p</i> = 0.0121), while the c.-251T allele frequencies were similar (54% vs. 51.5%, <i>p</i> = 0.4955). Serum IL-8 concentrations, measured using ELISA, were higher in IBD patients with the c.91 GG genotype compared to healthy controls (mean, 70.02 vs. 51.5 pg/ml, <i>p</i><0.01) and patients with c.91 GT (mean, 61.73 pg/ml). Moreover, clinical data indicated that carriers of the c.91T variant need more often corticosteroids and surgical treatment of the disease than GG homozygous IBD patients.</p><p><strong>Conclusion: </strong>This suggest that the <i>CXCL8</i> c.91T allele may influence IBD manifestation and the course of the disorders in Polish patients, potentially serving as a novel target for future studies and therapeutic approaches.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1562618"},"PeriodicalIF":5.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"sCD40 and sCD40L as candidate biomarkers of rheumatic diseases: a systematic review and meta-analysis with meta-regression.","authors":"Angelo Zinellu, Arduino A Mangoni","doi":"10.3389/fimmu.2025.1479904","DOIUrl":"10.3389/fimmu.2025.1479904","url":null,"abstract":"<p><p>There is an ongoing search for novel biomarkers to enhance diagnosing and monitoring patients with rheumatic diseases (RDs). We conducted a systematic review and meta-analysis to investigate the potential role of the soluble cluster of differentiation 40 (sCD40) and sCD40 ligand (sCD40L), involved in humoral and cellular immune response, as candidate biomarkers of RDs. We searched PubMed, Web of Science, and Scopus from inception to 30 June 2024 for studies investigating circulating sCD40 and sCD40L concentrations in RD patients and healthy controls. We assessed the risk of bias using the Joanna Briggs Institute Critical Appraisal Checklist for analytical studies and the certainty of evidence using the Grades of Recommendation, Assessment, Development and Evaluation Working Group system. Compared to controls, RD patients had significantly higher sCD40L (31 studies; standard mean difference, SMD=0.87, 95% CI 0.60 to 1.13, p<0.001; low certainty of evidence) and sCD40 (five studies; SMD=1.32, 95% CI 0.45 to 2.18, p=0.003; very low certainty of evidence) concentrations. In meta-regression and subgroup analysis, the effect size of the between-group differences in sCD40L was significantly associated with sample size, mean RD duration, specific RD, biological matrix assessed, and analytical method used. By contrast, there were no associations with age, sex, C-reactive protein, erythrocyte sedimentation rate, use of disease-modifying antirheumatic drugs or glucocorticoids, or geographical location. There were no significant differences in sCD40L concentrations between RD patients with and without active disease (eight studies; SMD=0.12, 95% CI -0.09 to 0.33, p=0.26; very low certainty). By contrast, sCD40 concentrations were significantly higher in RD patients with active disease (three studies; SMD=0.36, 95% CI 0.08 to 0.84, p=0.013; very low certainty). Our systematic review and meta-analysis suggests the potential role of sCD40 and sCD40L as candidate biomarkers to detect the presence of RDs (sCD40 and sCD40L) and monitor disease activity (sCD40). Large, appropriately designed prospective studies in a wide range of RDs are warranted to investigate whether measuring sCD40 and sCD40L can significantly improve the performance of currently available diagnostic criteria and serological biomarkers. (PROSPERO registration number: CRD42024577430).</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/PROSPERO/view/CRD42024577430, identifier PROSPERO CRD42024577430.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1479904"},"PeriodicalIF":5.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: Successful immune checkpoint inhibitor rechallenge after sintilimab-induced Guillain-Barré syndrome.","authors":"Lin Ye, Wan Rong Yue, Hao Shi, Jian Ren Li, Yu Ya Qun","doi":"10.3389/fimmu.2025.1546886","DOIUrl":"10.3389/fimmu.2025.1546886","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have revolutionized hepatocellular carcinoma (HCC) treatment, while immune-related adverse events (IRAEs) pose significant challenges. We report a 60-year-old male with unresectable HCC who developed Guillain-Barré syndrome (GBS), a rare but severe neurologic complication, after three cycles of sintilimab plus bevacizumab biosimilar and conventional transarterial chemoembolization (c-TACE). The patient presented with progressive ascending weakness, reaching symmetric quadriparesis with proximal muscle strength of 2/5 in upper limbs and 1/5 in lower limbs. Following sintilimab discontinuation, treatment with intravenous immunoglobulin (2 g/kg) and oral prednisone (30 mg/day) achieved complete neurological recovery within one month. Given the patient's favorable initial tumor response and strong request, immunotherapy was cautiously reinstated using tislelizumab after thorough clinical evaluation. Following four cycles of treatment, significant tumor response enabled successful conversion surgery with major pathological response (necrosis rate >70%). With 26-month survival and no evidence of recurrence, this case demonstrates the potential feasibility of ICI rechallenge with an alternative PD-1 inhibitor following sintilimab-induced GBS. Our experience suggests that ICI-related neurological adverse events may be drug-specific rather than class-specific, potentially providing valuable treatment options for patients showing favorable tumor response despite experiencing severe IRAEs, though larger studies are needed for validation.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1546886"},"PeriodicalIF":5.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}