BMC Immunology最新文献

{"title":"Prognostic value of systemic immune-inflammation index to albumin ratio (SAR) for long-term all-cause mortality in sepsis survivors: evidence from a multicenter cohort with up to 6 years of follow-up.","authors":"Yanni Tan, Minghui Wu, Zhenwei Zhai, Quan Lu, Haolun Wang, Jingxia Sun, Qiu Wang, Junyu He, Jinming Yu, Jianhao Huang, Wenxin Chu, Wensheng Lu","doi":"10.1186/s12865-026-00799-8","DOIUrl":"10.1186/s12865-026-00799-8","url":null,"abstract":"<p><p>OBJECTIVES: Patients recovering from sepsis still face a higher long-term mortality risk. This study aims to explore the association between the systemic immune-inflammation index-to-albumin ratio (SAR) and the risk of long-term all-cause mortality (up to 6 years) in sepsis survivors. METHODS: Between January 2017 and December 2022, 461 participants with sepsis recurrence-free status for at least 3 months following the first-episode sepsis cure from Nanning Third People’s Hospital, Guangxi Medical Sciences Academy and the People’s Hospital of Guangxi Zhuang Autonomous Region, were enrolled. Participants were categorized into three groups based on SAR tertiles: low-level (< 32.15, n = 153), moderate-level (32.15–80.57, n = 154), and high-level (> 80.57, n = 154). All participants were followed up every 3 months for a median of 36 months up to 6 years. The relationships between SAR and all-cause mortality risk were analyzed. RESULTS: Of the 461 participants, 177 (38.4%) died. Multivariable Cox regression analysis showed that the high-level SAR group had a higher risk of all-cause mortality in model III (P = 0.014). Subgroup stratification analysis revealed that when grouped by SAR level tertiles (with the lowest tertile as the reference baseline for all-cause mortality, a hazard ratio (HR) = 1), each subsequent tertile increase in SAR level was associated with a 21.9% higher risk of all-cause mortality in patients aged ≥ 65 years (HR = 1.219, 95% CI = 0.954–1.558, P for interaction < 0.001), and a 26.1% higher risk in those with cardiovascular and cerebrovascular complications (HR = 1.261, 95% CI: 0.925–1.719, P for interaction < 0.001), respectively. Kaplan-Meier analysis indicated that higher SAR levels were associated with lower survival probability (log-rank, P = 0.00025). The restricted cubic spline (RCS) model identified an inverted J-shaped dose-dependent relationship between SAR level and all-cause mortality risk (P for overall < 0.0001). Receiver operating characteristic (ROC) analysis demonstrated an optimal SAR cutoff value of 113.561 for predicting all-cause mortality. Decision curve analysis (DCA) confirmed that SAR provided a greater net clinical benefit than existing indicators, such as the systemic immune-inflammation index (SII), red blood cell distribution width (RDW), and lymphocyte to high-density lipoprotein cholesterol ratio (LHR). CONCLUSION: The findings suggest that SAR may serve as a potential cofactor, alongside age and cardiovascular comorbidities, in clinical decision-making regarding long-term all-cause mortality risk in sepsis survivors.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":" ","pages":"8"},"PeriodicalIF":2.9,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12860170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970570","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":"Upregulation of miR-223 by SIRT1 attenuates the inflammatory response in neonatal sepsis.","authors":"Anjian Yan, Chang Lu, Xuening Wang","doi":"10.1186/s12865-025-00793-6","DOIUrl":"10.1186/s12865-025-00793-6","url":null,"abstract":"<p><strong>Background: </strong>The diversity of clinical symptoms of neonatal sepsis leads to difficulties in diagnosis, and the treatment is limited. This study aims to investigate the role of the SIRT1/miR-223 signaling axis in neonatal sepsis.</p><p><strong>Methods: </strong>100 neonates with sepsis and 100 healthy infants were included in this study. The RT-qPCR was used to detect RNA and inflammatory factor levels in serum. Peripheral blood neutrophils were isolated by gradient centrifugation. LPS-stimulated neutrophils were detected for MPO activity and inflammatory factor expression. Neutrophils were transfected with miR-223 oligonucleotide and SIRT1-related plasmid to detect changes in neutrophil-related parameters.</p><p><strong>Results: </strong>Neonates with sepsis had a significantly stronger inflammatory response than healthy infants, and the expression of miR-223 and SIRT1 in the serum was remarkably reduced. ROC curves showed that miR-223 had a diagnostic value for neonatal sepsis. The expression of miR-223 and SIRT1 was notably reduced in the model cells, and overexpression of miR-223 attenuated the inflammatory response in the LPS-induced neutrophil. Overexpression of SIRT1 could alleviate the enhanced inflammatory response due to inhibition of miR-223.</p><p><strong>Conclusion: </strong>Overexpression of SIRT1 upregulated miR-223 expression, which attenuated the LPS-induced neutrophil activity and inflammatory response. The SIRT1/miR-223 signaling axis provides a potential therapeutic target for the clinical management of neonatal sepsis.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":" ","pages":"11"},"PeriodicalIF":2.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12882404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145942279","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":"Retrospective, single-center analysis of autoimmune hepatitis in Yemeni adults: clinical features, treatment, and outcomes.","authors":"Alariqi Reem, Al-Shami Abdulsalam, Afrah Al-Asbahy, Khalid Aldhorae, Wadee Abdullah Al-Shehari","doi":"10.1186/s12865-025-00796-3","DOIUrl":"10.1186/s12865-025-00796-3","url":null,"abstract":"<p><strong>Background: </strong>Autoimmune hepatitis (AIH) is a chronic liver disease in which the immune system of the body unintentionally targets liver cells, resulting in inflammation, liver damage, and cirrhosis if treatment is not received. Although the precise origin of AIH remains unknown, experts believe that environmental and genetic factors play significant roles in its pathogenesis. This study describes the clinical, biochemical, and long-term outcomes of patients with autoimmune hepatitis (AIH) at the Science and Technology Hospital in Sana'a, Yemen.</p><p><strong>Methodology: </strong>This was a retrospective, single-center study.</p><p><strong>Participants: </strong>All patients with AIH diagnosed at the Science and Technology Hospital between 2019 and 2024 were included.</p><p><strong>Results: </strong>Most patients were male (18 of 25, 72%). All patients displayed common signs and symptoms of AIH, including hepatomegaly, vomiting, jaundice, and abdominal distention. In addition to positive antinuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), the majority of individuals showed increased AST levels. The most prevalent hematological abnormalities were thrombocytopenia (64%) and anemia (56%). Regarding the outcome after hospital admission, 60% of cases improved, 12% were discharged against medical advice, 8% died, and 20% had unknown outcomes.</p><p><strong>Conclusion: </strong>Autoimmune hepatitis affects patients of Yemeni descent. The most common symptom is jaundice. Only Type I AIH was observed in this cohort, and the mortality rate reached 8%.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":" ","pages":"9"},"PeriodicalIF":2.9,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12870425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916842","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":"Lactate dehydrogenase to albumin ratio as a convenient parameter for predicting the severity of Behçet disease: a cross-sectional study.","authors":"Erdal Pala, Mustafa Bayraktar","doi":"10.1186/s12865-025-00706-7","DOIUrl":"10.1186/s12865-025-00706-7","url":null,"abstract":"<p><strong>Background: </strong>We investigated whether the ratio of lactate dehydrogenase (LDH) to albumin could be used as a diagnostic marker for Behçet's disease compared to the healthy population and as a marker to assess the severity and activity of the disease.</p><p><strong>Methods: </strong>The research was conducted as a cross-sectional study. Patients aged 18-69 years presenting to the Behçet's disease Outpatient Clinic over a three-year period and healthy individuals with a similar age and gender distribution formed the two study groups. LDH and albumin levels, and the LDH/albumin ratio were compared between the groups.</p><p><strong>Results: </strong>The study was conducted in 349 people, 160 patients with Behçet's disease and 189 healthy controls. The LDH/albumin ratio was significantly higher in the Behçet's group than in the control group. This ratio was significantly different according to the severity of the disease, the presence of genital ulcers, papulopustular lesions and joint involvement (p < 0.05). Duration of symptoms was positively correlated with LDH/albumin ratio values (r = 0.259, p = 0.001). ROC analysis of the LDH/albumin ratio in the severe versus not severe groups based on Behçet's disease severity showed an area under the curve (AUC) of 0.704 (95% CI: 0.586-0.821) and a cut-off value of 57.46, with a sensitivity of 57.7% and specificity of 72.4%.</p><p><strong>Conclusion: </strong>The LDH/albumin ratio is a promising parameter in patients diagnosed with Behçet's disease compared to healthy controls, with a cut-off value of 57.46 for distinguishing severe from non-severe disease.</p><p><strong>Trial registration: </strong>This study was registered under ID number NCT06276829 (Study Record Dates:18.02.2024).</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"27 1","pages":"1"},"PeriodicalIF":2.9,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12781827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916811","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":"TZ1391: a computationally designed circular mRNA multi-epitope vaccine candidate against Mycobacterium tuberculosis via TLR3 immunomodulation.","authors":"Awais Ali, Abdulaziz Alamri, Vipin Kumar Mishra, Aigul Utegenova, Gulsum Askarova, Aliya Baiduissenova, Aigul Dusmagambetova","doi":"10.1186/s12865-025-00795-4","DOIUrl":"10.1186/s12865-025-00795-4","url":null,"abstract":"<p><p>Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major global health burden due to latent infection, multidrug resistance, and the limited efficacy of the BCG vaccine. To address this challenge, we computationally designed and evaluated a circular mRNA-based multi-epitope vaccine candidate, TZ1391. Five experimentally validated M. tuberculosis antigens (ESAT-6, CFP-10, Ag85B, PPE18, and HspX) were used to predict immunodominant cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B-cell epitopes. Three vaccine constructs (MTB-C1, MTB-C2, and MTB-C3) were assembled by integrating 20 CTL, 20 HTL, and 20 B-cell epitopes with appropriate linkers, PADRE sequence, and innate immune adjuvants. Structural modeling using AlphaFold2 and GalaxyRefine confirmed stable, native-like conformations for all constructs, with MTB-C3 showing the highest structural quality (GDT-HA = 0.8782; RMSD = 0.646 Å) and the greatest number of stabilizing disulfide bonds. Molecular docking against TLR3, TLR4, and TLR8 identified two top-performing candidates. MTB-C3 exhibited the strongest interaction with TLR3, achieving the lowest HDock score (− 480.53) and highest confidence score (0.9987), while MTB-C2 showed optimal binding to TLR4 (ClusPro score − 1488.6; confidence 0.9700). Despite favorable TLR4 engagement by MTB-C2, MTB-C3 was prioritized as the lead candidate (TZ1391) due to its superior structural stability, reduced conformational fluctuations during molecular dynamics simulations, and stronger TLR3 binding free energy (ΔG_bind = − 173.25 ± 7.9 kcal/mol). Immune simulations further predicted that TZ1391 elicits a robust Th1-biased response, characterized by sustained IgG production, strong IFN-γ and IL-2 induction, and durable immune memory. Overall, the strong TLR3-mediated interaction, combined with enhanced structural stability and favorable immunogenic profiles, establishes TZ1391 as a promising multi-epitope vaccine candidate for further experimental validation against tuberculosis.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12930736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896169","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":"Investigating monoclonal antibody against cytokeratin 19 tumor marker.","authors":"Mohammad Amin Momeni-Moghaddam, Javad Mohammadnejad, Hossein Ghahremani, Shahnaz Khaghani, Nariman Moradi, Amin Daemi, Gülüzar Özbolat, Yusuf Döğüş, Seyyedeh Touran Hosseini","doi":"10.1186/s12865-025-00792-7","DOIUrl":"10.1186/s12865-025-00792-7","url":null,"abstract":"<p><p>Cytokeratin 19 (CK 19) is a member of the intermediate filaments that are widely expressed in thyroid, breast, colon, small and non-small cell lung, and prostate cancer cells. This paper aims to produce the monoclonal antibody against CK 19. Recombinant CK 19 was used to immunize of two 6–8 weeks old female Balb/c mice. For the first injection, recombinant antigen was mixed with the complete Freund′s Adjuvant, and for the second and third injections, mixed with the Incomplete Freund′s Adjuvant. Injections were performed at intervals of 15 days. Four days after the third injection, titration of mice serum was determined using indirect ELISA and better-immunized mice selected for fusion. Intravenous (IV) injection was performed 4 days before the fusion. The spleen cells of the mice were fused with sp2/0 cells using 50% v/v polyethylene glycol (PEG) and cells were suspended in HAT (Hypoxanthine-Aminopterin-Thymidine) medium. Supernatants of hybridoma cells were screened for antibody secretion by indirect ELISA. Two stable hybridomas were obtained among 78 hybridoma clones that reacted with the recombinant CK 19 by indirect ELISA. These hybridoma cells were monoclonal twice by limiting dilution. Besides, immunization by recombinant CK 19 led to the obtaining of two stable monoclonal antibodies against this antigen. Western blotting with HT-29 cell line demonstrated a band of upper than 43 kDa. Result of HepG2 indicated a band of lower than 45 kDa while MCF7 bands of 45 kDa and higher were observed for MCF7. A431 cell line was epidermoid carcinoma, as CK 19 did not exist in the epidermis, therefore no band was observed in A431 cell line.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":" ","pages":"7"},"PeriodicalIF":2.9,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12860061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846213","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":"The relationship between the biological biomarker lnc-DC and female patients with Sjögren's disease.","authors":"Beibei Zu, Yu Fu, Feng Gu, Peng Wang, Shixing Wang, Yan Liu, Jiao Zhang, Yanhong Chen","doi":"10.1186/s12865-025-00787-4","DOIUrl":"10.1186/s12865-025-00787-4","url":null,"abstract":"<p><p>OBJECTIVE: Laboratory diagnostic markers and clinical presentations of Sjögren’s disease (SjD) may vary by sex. This study aimed to investigate the association between lnc-DC expression and female SjD and to evaluate its potential as a diagnostic biomarker in female SjD patients. METHODS: 599 SjD patients were retrospectively analyzed in this cohort, additionally 337 healthy adults without autoimmune diseases served as the healthy control group (HC). Adjusted p - values are reported for all exploratory analyses. Associations between diverse clinical parameters and SjD occurrence among female SjD patients were assessed using Cox proportional hazards models. To account for multiple hypothesis testing across 40 comparisons, we applied the Benjamini-Hochberg false discovery rate (FDR) correction with q = 0.05. Subsequently, receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic performance of lnc-DC expression levels in distinguishing female SjD patients. RESULTS: After a retrospective observation for median 44 months (Interquartile Range (IQR): 35–55 months), symptoms such as dry mouth, joint pain, reduced tear flow, elevated IgM concentrations, increased ESSDAI scores, and higher detection rates of rheumatoid factor (RF), anti-Ro52 antibody, and anti-SSA antibody were significantly more prevalent among female patients (all p < 0.05). Moreover, female participants exhibited substantially increased levels of lnc-DC expression (p < 0.001). In contrast, males displayed a higher prevalence of parotid gland enlargement and interstitial lung disease (ILD) (both p < 0.001). Cox proportional hazards models identified elevated lnc-DC expression as an independent predictor for SjD development in females (p < 0.001). After FDR correction, elevated lnc-DC remained significantly associated with SjD status (adjusted p < 0.001). Other biomarkers did not survive correction (adjusted p > 0.05). Additionally, ROC curve analysis demonstrated that elevated lnc-DC levels effectively distinguished female SjD patients, with an area under the curve (AUC) of 0.83, sensitivity of 78.64%, and specificity of 73.61%, p < 0.001. CONCLUSIONS: Female SjD patients exhibited significantly elevated lnc-DC expression. When integrated with conventional serological markers, lnc-DC enhanced SjD diagnostic accuracy. These findings suggest lnc-DC as a sex-specific adjunct biomarker for SjD clinical diagnosis.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":" ","pages":"6"},"PeriodicalIF":2.9,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12849065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843282","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":"Identification of potential characteristic genes in sepsis utilizing RNA sequencing and gene silence.","authors":"Hongying Cao, Nianying Qin, Yiling Zhai, Chunyang Dong, Zhou Huang, Dongling Huang, Jincheng Li, Jie Yang, Fan Wang, Wanxia Wei, Wei Wang","doi":"10.1186/s12865-025-00778-5","DOIUrl":"10.1186/s12865-025-00778-5","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Sepsis represents a serious condition involving organ dysfunction that can be life-threatening, posing a significant threat to human health. The mortality rate associated with sepsis ranges from 10% to 40%, with severe cases or those involving septic shock exhibiting mortality rates exceeding 50%.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Gene sequencing took place on the blood samples that were collected both healthy volunteers and septic patients in this study. Advanced methodologies, including bioinformatics analysis, quantitative PCR (qPCR), meta-analysis, and single-cell localization analysis, were employed to identify potential biomarkers associated with the immunomodulation of sepsis. The identified molecular markers were further validated through the establishment of a sepsis cell model, gene silence techniques, and an ELISA test experiments to assess inflammatory factors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this study, 23 individuals with sepsis and 10 healthy volunteers as controls, and peripheral blood samples were collected. The blood specimens were processed with the assistance of BGI for comprehensive gene sequencing. Post-sequencing, the data underwent quality control measures and were subsequently analyzed using the online platform iDEP 2.01 ( http://bioinformatics.sdstate.edu/idep/ ) to identify differentially expressed genes. Conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses on the identified differentially expressed genes.To elucidate core genes from multiple perspectives, a PPI network was created with the help of the STRING database ( https://cn.string-db.org/),facilitatin g the examination of gene interactions in terms of protein. Following the recognition of core genes, sepsis-associated data sets were obtained from the Gene Expression Omnibus (GEO) public database. Specifically, the transcriptional expression of the gene S100A11 was analyzed using meta-analysis techniques, and its survival curve was subsequently evaluated.The S100A11 gene, identified through screening, was analyzed using an online visualization system to determine its single-cell localization. Initial findings indicated that the gene is predominantly expressed in macrophages. (THP-1 cells) are known as a human monocytic cell line utilized in studies.We cultured THP-1 cells and differentiated into macrophages, followed by stimulation and transfection with the S100A11 gene. The interference effect of S100A11 was assessed using quantitative fluorescence PCR (qPCR). Subsequently, THP-1 cells were cultured to establish a septic cell model, and S100A11 gene silence experiments were conducted, categorizing the samples into control, sepsis, and gene silence sepsis groups. ELISA was employed to assess the concentrations of the inflammatory cytokine IL-1β, TNF-α, and IL-6.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Results demonstrated that S100A11 is highly expressed in sepsis and is primarily l","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"99"},"PeriodicalIF":2.9,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12729154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145826897","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":"T cell immunometabolic dysfunction in a mouse model of cecal ligation and puncture-induced sepsis.","authors":"Xiaoju Liu, Mai Liting, Peiyu Li, Zhong Chen, Zhijian Yu","doi":"10.1186/s12865-025-00790-9","DOIUrl":"10.1186/s12865-025-00790-9","url":null,"abstract":"<p><strong>Background: </strong>T lymphocyte dysfunction is closely associated with immunosuppression in sepsis, whereas the underlying mechanisms are not fully understood.</p><p><strong>Results: </strong>In this study, we established a mouse model of cecal ligation and puncture (CLP)-induced sepsis and observed immunometabolic alterations in splenic T cells. Serum energy metabolites related to glycolysis and the tricarboxylic acid (TCA) cycle were imbalanced. Splenic T cells from septic mice showed a shift in subset distribution, with decreased naïve T cells and increased effector populations, along with concurrent activation and exhaustion phenotypes. Notably, mitochondrial mass and mitochondrial membrane potential were significantly diminished in both CD4⁺ and CD8⁺ T cell, correlated with increased programmed cell death protein 1 (PD-1) expression. Transmission electron microscopy further confirmed mitochondrial morphological alterations in CLP-derived CD3⁺ T cells. Furthermore, seahorse assays demonstrated impaired metabolic reprogramming capacity in activated CLP splenic CD3⁺ T cells, with suppressed glycolytic and oxidative phosphorylation responses. This impairment was coupled with reduced fold-increases in mitochondrial mass and mitochondrial membrane potential levels upon activation in both CD4⁺ and CD8⁺ T cell compared to controls. Clinically, peripheral T cells from septic patients showed elevated CD69 and PD-1 expression, a significant increase in CD39 and a decrease in CD73, increased mitochondrial mass and decreased mitochondrial membrane potential, particularly in those with septic shock.</p><p><strong>Conclusions: </strong>Our findings provide several layers of T cell dysfunction in sepsis, linking subset redistribution, an exhausted phenotype, mitochondrial impairment, and reduced proliferative capacity, suggesting that future therapeutic interventions aiming to reverse sepsis-induced immunosuppression may require a combinatorial approach.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":" ","pages":"3"},"PeriodicalIF":2.9,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12802186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145713265","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":"Mp1p antigen as a sensitive diagnostic marker for early detection and treatment monitoring of Talaromyces Marneffei infection.","authors":"Jinding Zheng, Cheng Zhang, Liulu Zhang, Xiaofeng Wang, Yinxue Lu, Yisi Lei, Ke Liang, Rongrong Yang, Xiaoping Chen, Xinhua Luo, Xien Gui","doi":"10.1186/s12865-025-00775-8","DOIUrl":"10.1186/s12865-025-00775-8","url":null,"abstract":"<p><p>BACKGROUND: Talaromyces marneffei (TM) is a life-threatening opportunistic fungal pathogen, particularly in individuals with advanced HIV/AIDS. Early and accurate diagnosis remains challenging due to the limited sensitivity and specificity of conventional microbiological and antigen-based tests. Mp1p, a secreted TM-specific virulence protein, has emerged as a promising target for serological diagnosis. This study aimed to evaluate the diagnostic performance of Mp1p antigen and antibody detection using ELISA in sera from HIV infected patients with confirmed TM infection. METHODS: A total of 36 confirmed TM-infected patients (including fungemia and non-fungemia cases), 269 HIV/AIDS patients with fever but without TM infection, 37 cryptococcosis patients, and 218 healthy blood donors were enrolled from two tertiary hospitals in China (2020–2024). Recombinant Mp1p protein was expressed and purified to develop Mp1p antigen and antibody ELISAs. Diagnostic sensitivity and specificity were calculated. Serial samples before and after antifungal therapy were evaluated to determine the utility of Mp1p antigen and antibody levels in treatment monitoring and recurrence detection. Results were compared with established diagnostic tools, including galactomannan (GM) and cryptococcal antigen (CrAg) assays. RESULTS: Mp1p antigen ELISA demonstrated high sensitivity (94.4%) and specificity (98.5%) for TM infection. In contrast, Mp1p antibody ELISA had lower sensitivity (25.0%) but equally high specificity (98.5%). Mp1p antigen levels significantly declined after amphotericin B (AMB) treatment (mean OD₄₅₀: 1.654 ± 0.723 pre-treatment vs. 0.355 ± 0.488 post-treatment; p < 0.0001), supporting its role in treatment monitoring. Antigen levels were significantly higher in fungemic versus non-fungemic patients (p = 0.001). Among initially antibody-negative patients, 56.3% seroconverted within one year, suggesting delayed antibody response. Mp1p antigen levels rebounded in one relapsed patients before clinical deterioration, while antibody levels did not change, highlighting the antigen's potential for early relapse detection. CONCLUSIONS: Mp1p antigen ELISA is a highly sensitive and specific tool for early diagnosis and therapeutic monitoring ofTM infection in HIV-infected patients. Its performance exceeds current serological assays and is especially valuable in identifying fungemia and potential relapse. In contrast, Mp1p antibody detection is limited in early-stage diagnosis due to delayed seroconversion. Incorporating Mp1p antigen testing into clinical workflows may significantly improve patient outcomes through earlier intervention.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"98"},"PeriodicalIF":2.9,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12690885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145713243","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}