Frontiers in Immunology最新文献

{"title":"Glutamine metabolic reprogramming in acute and chronic kidney diseases: mechanistic insights and therapeutic implications.","authors":"Ruotong Xu, Jin Zhao, Minna Liu, Yifan Qiao, Xiaoxuan Ning, Shiren Sun","doi":"10.3389/fimmu.2026.1939528","DOIUrl":"10.3389/fimmu.2026.1939528","url":null,"abstract":"<p><p>Acute kidney injury (AKI) and chronic kidney disease (CKD) are common clinical disorders that have high incidence and mortality. Their pathogenesis and the mechanisms underlying AKI-to-CKD progression remain unclear. Metabolic reprogramming has emerged as a core mechanism driving the onset and progression of kidney diseases. Glutamine (Gln) metabolism, a central component of renal energy metabolism, not only maintains acid-base balance and cellular homeostasis but also actively participates in pathophysiological processes including ischemic injury, oxidative stress, inflammatory regulation and fibrosis. Multi-omics studies have revealed stage-specific alterations in Gln metabolism-associated signatures during kidney injury. In AKI, altered Gln levels and redox-related metabolites may suggest disturbances in metabolic pathways, whereas in CKD, elevated glutaminase 1 (GLS1) expression and glutaminolysis-associated metabolic reprogramming are associated with fibrosis. Gln, as an immunonutrient, also serves as a critical energy substrate to sustain the proliferation, activation, and effector functions of immune cells. Gln metabolism may reshape the immune microenvironment within the injured kidney, thereby modulating disease progression. Targeting the Gln metabolic axis may offer new therapeutic insights for AKI and CKD. However, the changes in Gln metabolism and its consequent immunometabolic effects during the AKI-to-CKD transition remain poorly understood. This narrative review aims to provide a comprehensive overview of the dynamic changes in Gln metabolism during acute and chronic kidney diseases, its stage-specific mechanisms, and its potential as a therapeutic target. We also seek to provide a theoretical basis for developing novel biomarkers and targeted therapies based on Gln metabolic reprogramming.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1939528"},"PeriodicalIF":7.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13700215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265821","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":"Cerebrospinal fluid metagenomic next-generation sequencing for culture-negative anaerobic central nervous system infection involving <i>Prevotella oris</i>: attribution challenges in low-biomass specimens.","authors":"Yan Li, Minghua Fan, Yuyuan Hu, Yuhang Yang, Wenyuan Li, Wei Zhang, Yanhong Wang","doi":"10.3389/fimmu.2026.1896093","DOIUrl":"10.3389/fimmu.2026.1896093","url":null,"abstract":"<p><p>Anaerobic central nervous system (CNS) infections are uncommon but diagnostically difficult because fastidious organisms may be suppressed by empirical antimicrobial therapy and conventional cultures may remain negative. Cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) can recover microbial nucleic acids in this setting, but low microbial biomass creates a central attribution problem: a detected organism may represent active infection, introduced commensal DNA, laboratory background, or bioinformatic misclassification. This narrative Mini Review uses <i>Prevotella oris</i> as a representative oral anaerobe to examine that problem. We synthesize evidence on low-biomass CSF specimen processing and sequencing strategies, including nanopore sequencing, whole-genome amplification, and targeted approaches, alongside contamination control, sequence-level and taxonomic credibility, host-response immunology, neuroimaging and source concordance, antimicrobial timing, and discordant clinical scenarios. We then organize these established principles into an expert-informed two-step pathway that separates technical signal credibility from clinical attribution and explicitly preserves an indeterminate state when evidence conflicts. <i>P. oris</i> is positioned as a useful model of the plausible contaminant paradox rather than as a pathogen with a unique CNS phenotype. We also outline syndrome-based management, source control, and treatment-duration principles. The framework is conceptual and non-validated; its purpose is transparent reasoning and reporting, not diagnostic scoring or probability estimation.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1896093"},"PeriodicalIF":7.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149266048","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":"Donor-recipient Hepatitis B serological patterns and post-transplant HBV events in pediatric living donor liver transplantation: a single-center retrospective cohort with a nested case series.","authors":"Ying Le, Haifeng Tang, Quanhai Zhang, Jiajun Weng, Lianbin Huang, Xiaoke Dai, Mingman Zhang","doi":"10.3389/fimmu.2026.1977829","DOIUrl":"10.3389/fimmu.2026.1977829","url":null,"abstract":"<p><strong>Background: </strong>The combined effects of donor hepatitis B core antibody (anti-HBc) status and recipient pre-transplant hepatitis B surface antibody (anti-HBs) levels on post-transplant HBV events remain unclear in pediatric living donor liver transplantation (LDLT).</p><p><strong>Methods: </strong>We retrospectively analyzed pediatric LDLT recipients transplanted between May 2018 and June 2023. The primary outcome was the first post-transplant hepatitis B surface antigen (HBsAg)-positive result, with death treated as a competing event. Recipients were stratified by donor anti-HBc status and recipient anti-HBs level (≥100 vs <100 mIU/mL). Antiviral prophylaxis with entecavir (0.015 mg/kg once daily) was given only to recipients of anti-HBc-positive grafts, and hepatitis B immune globulin was not used. Cumulative incidence was compared using Gray's test, and associated factors were evaluated using Fine-Gray regression.</p><p><strong>Results: </strong>Among 229 recipients, 14 (6.1%) developed HBV events. Events occurred in 0 of 97 recipients with an anti-HBc-negative donor and anti-HBs ≥100 mIU/mL (G1), 3 of 67 with an anti-HBc-negative donor and anti-HBs <100 mIU/mL (G2), 2 of 29 with an anti-HBc-positive donor and anti-HBs ≥100 mIU/mL (G3), and 9 of 36 with an anti-HBc-positive donor and anti-HBs <100 mIU/mL (G4); the corresponding 5-year cumulative incidences were 0%, 4.5%, 6.9% and 25.0% (global Gray's test, P<0.001). Donor anti-HBc positivity (sHR, 8.28; 95% CI, 2.27-30.28; P = 0.001) and recipient anti-HBs <100 mIU/mL (sHR, 6.02; 95% CI, 1.32-27.55; P = 0.021) were independently associated with HBV events, although the wide confidence intervals reflect the small number of events (n = 14) and the magnitude of these estimates should be interpreted with caution.</p><p><strong>Conclusions: </strong>Donor anti-HBc positivity and low recipient pre-transplant anti-HBs were independently associated with post-transplant HBV events after pediatric LDLT. Combined donor-recipient serological stratification identified a clear risk gradient and may support risk-adapted HBV surveillance and prevention.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1977829"},"PeriodicalIF":7.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265810","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":"Hypoxia-inducible factor-1α-mediated metabolic reprogramming in sepsis-associated organ dysfunction: organ-specific metabolic mismatch and therapeutic perspectives.","authors":"Yuge Wu, Jiantao Lu, Yue Mo, Yaoqi Xu, Xiaoxi Yan, Caifen Yan, Yingzhen Wang","doi":"10.3389/fimmu.2026.1998563","DOIUrl":"10.3389/fimmu.2026.1998563","url":null,"abstract":"<p><p>Sepsis-associated organ dysfunction arises from immune dysregulation, heterogeneous microcirculatory perfusion, impaired oxygen utilization, and cellular metabolic disturbances. Hypoxia-inducible factor-1α (HIF-1α) links oxygen sensing and inflammatory signaling to substrate use and mitochondrial function, but its effects vary with cell type, organ energy demand, and disease stage. This review uses metabolic flexibility and organ-specific metabolic mismatch to integrate these differences. Metabolic flexibility denotes the capacity to adjust energy-producing pathways during stress and restore efficient oxidative metabolism after stress subsides; mismatch develops when cellular energy production no longer meets immediate organ function or repair requirements. HIF-1α-related glycolysis supports early antimicrobial responses in myeloid cells and short-term hypoxic tolerance in some parenchymal cells. Persistent glycolysis combined with restricted pyruvate and fatty acid oxidation and impaired mitochondrial renewal may instead prolong inflammation and limit barrier repair, tubular transport, myocardial contraction, hepatic clearance, and neurological recovery. Differences among the lungs, kidneys, heart, intestine, liver, and brain indicate that global HIF activation or inhibition is unlikely to produce uniform benefit. Cell type-resolved localization, dynamic metabolic flux, mitochondrial function, and organ-level endpoints are therefore required to distinguish adaptive reprogramming from persistent bioenergetic dysfunction and to guide phase-matched metabolic intervention.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1998563"},"PeriodicalIF":7.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13697615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265846","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":"Early dynamics of eosinophils and the neutrophil-to-lymphocyte ratio are associated with severe immune-related adverse events during nivolumab therapy for metastatic renal cell carcinoma.","authors":"Ondřej Fiala, Jan Králíček, Jindřich Kopecký, Michal Vočka, Tomas Buchler, Hana Študentová, Jana Obertová, Beáta Rondzíková, Martin Matějů, Dominik Šafčák, Matej Hrnčár, Peter Priester, Martina Spisarová, Anežka Zemánková, Radka Lohynská, Michaela Tkadlecová, Lucie Grmelová, Petr Stránský, Bohuslav Melichar, Patrik Palacka, Alexandr Poprach","doi":"10.3389/fimmu.2026.1944728","DOIUrl":"10.3389/fimmu.2026.1944728","url":null,"abstract":"<p><strong>Background: </strong>Reliable biomarkers for characterization of the risk of severe immune-related adverse events (irAEs) during immune checkpoint inhibition remain lacking. We hypothesized that early dynamics of complementary complete blood count (CBC)-based immune biomarkers may be associated with severe immune toxicity. We therefore evaluated longitudinal changes in absolute eosinophil count (AEC) and neutrophil-to-lymphocyte ratio (NLR) in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab.</p><p><strong>Methods: </strong>This multicenter retrospective study included 503 patients with mRCC receiving nivolumab monotherapy in the second or later treatment line. Biomarker analyses were performed using a prespecified 28-day landmark design. AEC and NLR were evaluated at baseline, month 1, and as dynamic Low→High phenotypes, defined as transition from below the baseline upper-quartile threshold to the highest month-1 quartile. Multivariable logistic regression adjusted for age, sex, ECOG performance status, IMDC risk group, and treatment line.</p><p><strong>Results: </strong>Among 501 toxicity-evaluable patients, 57 (11.4%) developed grade 3-4 irAEs. Baseline AEC and NLR were not associated with severe irAEs. In contrast, the AEC Low→High phenotype was associated with severe irAEs after multivariable adjustment (adjusted odds ratio [aOR] 2.25, 95% confidence interval [CI] 1.02-4.97; P = 0.045), as was the NLR Low→High phenotype (aOR 2.77, 95% CI 1.25-6.17; P = 0.012). In a prespecified combined multivariable model, NLR remained independently associated with severe irAEs (aOR 2.81, 95% CI 1.25-6.30; P = 0.012), whereas the AEC association was attenuated (aOR 2.08, 95% CI 0.90-4.80; P = 0.085).</p><p><strong>Conclusions: </strong>Early dynamics of eosinophils and NLR, rather than baseline biomarker values, were associated with severe irAEs during nivolumab therapy. These findings suggest that eosinophil expansion and inflammatory remodeling may reflect aspects of early immune activation associated with clinically significant immune toxicity. Longitudinal assessment of routinely available CBC-based immune biomarkers therefore warrants prospective validation in cohorts with time-resolved toxicity assessment.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1944728"},"PeriodicalIF":7.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265791","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":"Metabolic stress and macrophage efferocytosis in osteoarthritis: mechanisms and therapeutic implications.","authors":"HaoYang Wu, DeChao Yuan, RenJian He, ShiWei Liu","doi":"10.3389/fimmu.2026.1999085","DOIUrl":"10.3389/fimmu.2026.1999085","url":null,"abstract":"<p><p>Metabolic disturbances contribute to osteoarthritis through mechanisms that extend beyond increased mechanical loading, yet their effects on inflammatory resolution remain incompletely understood. Macrophage efferocytosis-the recognition, engulfment, and degradation of apoptotic cells-provides a potential link between metabolic stress and persistent synovitis. This Mini Review examines how obesity and hyperglycemia disrupt synovial macrophage clearance and evaluates the rationale for therapeutic restoration. Human observations and experimental osteoarthritis studies implicate reduced growth arrest-specific 6 signaling and hyperglycemia-associated CD11b lactylation in defective apoptotic-cell recognition and uptake. Complementary evidence from other inflammatory conditions identifies membrane trafficking, mitochondrial adaptation, and lysosomal cargo processing as additional determinants of clearance competence. Importantly, glycolysis and lactate have context-dependent effects: although lactylation can impair recognition, adaptive lactate signaling supports repeated engulfment and expansion of pro-resolving macrophages. This distinction challenges indiscriminate glycolytic inhibition and favors interventions matched to the affected clearance step. Defective efferocytosis may amplify synovitis through persistence of cellular debris and loss of resolution-promoting signals, thereby creating an environment unfavorable to cartilage homeostasis. Emerging receptor-directed, metabolic, and intra-articular delivery strategies offer opportunities to restore clearance, but clinical validation remains necessary. Translation will require identification of susceptible macrophage populations, functional assessment of the complete efferocytic process, and demonstration that clearance recovery mediates meaningful improvements in joint structure and symptoms.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1999085"},"PeriodicalIF":7.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265806","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":"Gut microbiota-mediated tryptophan metabolic dysregulation in the comorbidity of inflammatory bowel disease and autism spectrum disorder: mechanisms and research progress.","authors":"Mingyu Lu, Yuxuan Chen, Hengli Zhou, Yingzhuo Lin","doi":"10.3389/fimmu.2026.1950055","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1950055","url":null,"abstract":"<p><p>The \"microbiota-gut-brain axis\" represents a critical link connecting various aspects of intestinal physiology, brain function, and behavioral performance. Among these, tryptophan metabolism abnormalities mediated by gut microbes through the gut-brain axis (GBA) have garnered widespread attention in the study of IBD-ASD comorbidity. This article reviews the current state of research on tryptophan metabolism abnormalities in IBD-ASD comorbidity, with a particular focus on the connection between peripheral and central tryptophan metabolic derangements mediated by gut microbes via the GBA. Furthermore, we summarize and analyze potential therapeutic targets and intervention strategies in this comorbid condition, integrating recent mechanistic studies and clinical evidence to provide a conceptual framework for understanding the potential mechanisms underlying IBD-ASD comorbidity. However, direct evidence from patients with confirmed IBD-ASD comorbidity remains limited at present, and further clinical studies are still needed to test this hypothesis.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1950055"},"PeriodicalIF":7.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265811","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":"Context dependent interactions between protozoan infections and cancer biology-a retrospective review.","authors":"Fanglei Yu, Zheng Wu, Yaru Huang, Xiaochen Qi, Jun Wu, Yuanhua Qin","doi":"10.3389/fimmu.2026.1968151","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1968151","url":null,"abstract":"<p><p>Protozoan infections can influence tumor biology through immune modulation, effects on tumor cells and vasculature, and changes in mucosal homeostasis. The supporting evidence, however, differs substantially among organisms and experimental settings. Selected studies of Toxoplasma gondii, Plasmodium species, and Trypanosoma cruzi demonstrate tumor suppression in cell and animal models, including immune activation, altered myeloid-cell function, and inhibition of angiogenesis. Associations between intestinal or urogenital protozoa and human cancers are mainly observational and do not establish carcinogenesis. Malaria associated with Plasmodium falciparum in holoendemic areas provides a distinct cancer-associated context that cannot be equated with experimental antitumor interventions. This narrative review distinguishes population associations, mechanistic observations, causal evidence within experimental models, and human therapeutic investigation. It evaluates strain or subtype, infection burden and duration, tissue tropism, host immune status, and observation timing as candidate modifiers rather than universally validated determinants. Direct tumor-cell effects, vascular effects, and host-immune-mediated effects are considered separately. Particular attention is given to inconsistent Trichomonas vaginalis and Blastocystis findings, limitations of murine models, confounding and reverse causation, and the safety of live-organism approaches in immunocompromised patients. Registered Plasmodium-based oncology studies demonstrate clinical investigation, but registration does not establish therapeutic benefit. Most engineered parasites and parasite-derived platforms discussed remain preclinical. The proposed framework organizes heterogeneous evidence and identifies testable questions for safer translational research; it does not imply that natural protozoan infection provides a predictable clinical benefit.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1968151"},"PeriodicalIF":7.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13691939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265795","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":"Acute lung injury: an integrated view of molecular drivers, immune dysregulation, and emerging therapeutic strategies.","authors":"Aihua Wang, Haizhao Liu, Chengfen Yin, Yawen Song, Yue Jin, Lei Xu, Siwei Wang, Jiaxin Li, Xiping Guo, Yongli Ma, Yutong Jin, Wei Liu, Ximo Wang","doi":"10.3389/fimmu.2026.1937966","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1937966","url":null,"abstract":"<p><p>Acute lung injury (ALI, a term widely used in preclinical animal studies, while the clinical definition of ALI was eliminated in the Berlin criteria) and its severe human clinical counterpart, acute respiratory distress syndrome (ARDS), constitute life-threatening clinical syndromes characterized by diffuse alveolar damage, pulmonary edema, and severe hypoxemia. These conditions are associated with dismal mortality rates and significantly impair patient survival and recovery. Over the past decades, advancements in critical care medicine and molecular biology have deepened our understanding of the pathological mechanisms underlying ALI and ARDS. Aberrantly activated signaling pathways and molecular and cellular events have emerged as key elements to decipher core pathogenic processes, identify early biomarkers, and develop novel therapeutic strategies. This review aims to provide a comprehensive overview of ALI and ARDS, encompassing their definition, historical context, epidemiology, and common etiological factors, with a focus on recent advances in pathological mechanisms, signaling pathways, epigenetic regulation, and therapeutic interventions. Treatment approaches include lung-protective ventilation, fluid management, targeted pharmacotherapy, mesenchymal stromal cell therapy, and nanomaterial-based delivery systems. These developments offer valuable insights into the complex mechanisms of preclinical ALI and human ARDS and contribute to the advancement of clinical diagnosis and treatment.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1937966"},"PeriodicalIF":7.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13693559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265867","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":"Integrated proteomic and metabolomic profiling characterizes tryptophan metabolic disturbance associated with mortality in ICU-admitted SFTS patients.","authors":"Li Chen, Puhui Liu, Chuanzhen Niu, Chenxiao Hao, Fengxue Zhu, Guangjie Wang, Huiying Zhao","doi":"10.3389/fimmu.2026.1898053","DOIUrl":"10.3389/fimmu.2026.1898053","url":null,"abstract":"<p><p>Severe fever with thrombocytopenia syndrome (SFTS), caused by Dabie bandavirus, is associated with high mortality among intensive care unit (ICU) patients; however, the integrated proteomic-metabolomic mechanisms underlying fatal outcomes remain poorly characterized. This prospective cohort study enrolled 68 patients with SFTS, who were admitted to the ICU and classified them as survivors (n = 33) or non-survivors (n = 35) according to their 28-day clinical outcomes. Untargeted metabolomic profiling using ultra-high-performance liquid chromatography-tandem mass spectrometry and quantitative proteomic profiling using data-independent acquisition mass spectrometry were performed on plasma samples collected at ICU admission. Multivariable analysis, pathway enrichment analysis, correlation analysis, and receiver operating characteristic (ROC) curve analysis were used to identify potential prognostic biomarkers and characterize molecular associations. Non-survivors exhibited more severe multi-organ injury and systemic inflammation. Metabolomic profiling revealed marked disruption of tryptophan metabolism: L-tryptophan levels were decreased, whereas kynurenine and its downstream metabolites (kynurenic acid [KA], 3-hydroxyanthranilic acid [3-HAA], xanthurenic acid [XA], and 5-hydroxyindolepyruvate [5-HIP]) were increased, suggesting activation of the kynurenine pathway. The four core tryptophan metabolites yielded a combined area under the curve (AUC) of 0.934 for predicting 28-day mortality and were correlated with indicators of renal function and coagulation. Proteomic profiling identified 200 differentially expressed proteins: proteins upregulated in survivors were enriched in the proteasome pathway, whereas those upregulated in non-survivors were enriched in the IL-17 pathway and other inflammatory and immune pathways. Integrated analysis revealed that the four tryptophan metabolites were associated with 20 differentially expressed proteins, six of which showed robust associations within outcome subgroups. Collectively, tryptophan metabolic disturbances coupled with inflammatory proteomic features may characterize fatal severe SFTS, and the identified metabolite-protein signatures may serve as promising prognostic biomarkers and potential therapeutic targets in critically ill patients.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1898053"},"PeriodicalIF":7.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13690963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244249","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}