Immunologic Research最新文献

{"title":"Transcriptomic analysis of lncRNA-miRNA-mRNA competing endogenous RNA regulatory networks in radiation-induced mouse thymic degeneration.","authors":"Fei Wang, Qing-Hua Yu, Xin-Ming Fan, Cun-Yang Guo, Si-Guang Xu, Wen-Bo Zhang, Ping Xu","doi":"10.1007/s12026-026-09805-y","DOIUrl":"10.1007/s12026-026-09805-y","url":null,"abstract":"<p><p>Excessive or inappropriate radiation can seriously harm organisms. Radiation-induced thymus injury (RITI) is a severe complication driven by dysregulated RNA networks. However, current studies have mostly focused on single non-coding RNAs or late pathological stages, and a complete competing endogenous RNA (ceRNA) regulatory network had not been constructed. The thymus tissues of C57BL/6 mice exposed to 6 Gy X-ray radiation for 24 h were analyzed by RNA-sequencing (RNA-seq) with library construction. We functionally annotated target messenger RNAs (mRNAs) and predicted long non-coding RNA (lncRNA) -targeted microRNAs (miRNAs) and miRNA-targeted mRNAs post-irradiation, to construct the lncRNA-miRNA-mRNA ceRNA regulatory axis. Furthermore, multiple experimental approaches including quantitative real-time PCR (qRT-PCR), western blotting, flow cytometry and CCK-8 cell viability assays were utilized to validate the involvement of the phosphatidylinositol 3-kinase (PI3K)-Protein Kinase B (PKB or AKT) pathway. The results revealed that after irradiation, 6214 mRNAs, 160 miRNAs, and 1999 lncRNAs were significantly upregulated while 2676 mRNAs, 165 miRNAs, and 941 lncRNAs were considerably downregulated. The most significantly altered Gene Ontology (GO) terms were angiogenesis and ameboid cell migration (Biological Process, BP), actin cytoskeleton and cell-cell junctions (Cellular Component, CC), as well as actin binding and phospholipid binding (Molecular Function, MF). A total of 333 cellular functions mediated by phosphatase and tensin homologue deleted on chromosome ten (PTEN) exhibited significant alterations, whereas 175 cellular functions regulated by 3-phosphoinositide-dependent protein kinase 1 (PDPK1) showed substantial changes. Key biological pathways, including cancer-associated pathways, the PI3K-AKT signaling pathway, the human papillomavirus infection pathway, the focal adhesion pathway, the Rap1 signaling pathway, and the cardiomyocyte calcium signaling pathway, were uncovered through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Based on the results of both GO enrichment analysis and KEGG pathway analysis, a consistent conclusion was drawn that RITI was closely associated with the PI3K-AKT signaling pathway. So the PI3K-AKT pathway was selected for experimental validation, which confirmed that it was a key regulatory pathway for thymic degeneration in RITI. A lncRNA-miRNA-mRNA ceRNA axis of RITI was successfully developed in a mouse model after irradiation. The PI3K-AKT pathway contributes to preventing radiation-induced cell death in RITI, and the differentially expressed RNAs in the initial stage of this injury may result in serious consequences.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging target antigen landscape for CAR T-cell therapy in solid tumors: current advances and future directions.","authors":"Debolina Chakraborty, Subhadip Kundu, Sudhir Kumar Rawal, Samson Mani","doi":"10.1007/s12026-026-09806-x","DOIUrl":"10.1007/s12026-026-09806-x","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T-cell therapy has achieved remarkable clinical success in hematologic malignancies but remains largely ineffective in solid tumors due to antigen heterogeneity, immune evasion, and dose-limiting toxicities. A central challenge is the identification of optimal target antigens that balance tumor specificity with therapeutic efficacy. In this review, we define the emerging antigenic landscape for CAR T-cell therapy in solid tumors through integrative curation and systems-level analysis. We reviewed 58 candidate targets spanning tumor-associated surface molecules, stromal and angiogenic components, immune checkpoints, and regulatory signaling nodes. Pathway enrichment reveals convergence on key oncogenic and immune regulatory circuits, including cell adhesion, receptor tyrosine kinase signaling, and PD-1/PD-L1 mediated immune suppression, underscoring their roles in tumor progression and immune escape. Notably, most prioritized targets localize to the plasma membrane and cell-cell interfaces, reinforcing their accessibility for CAR-based interventions. We further highlight advances in multi-antigen targeting, logic-gated CAR designs, and engineered resistance to immunosuppressive cues that collectively address tumor heterogeneity and functional exhaustion. By integrating antigen biology with emerging engineering strategies, this review provides a conceptual framework for rational target selection and combinatorial design. These insights advance the development of next-generation CAR T-cell therapies with improved precision and durability against solid tumors.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148436530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emapalumab plus conventional therapy with or without ruxolitinib for pediatric hemophagocytic lymphohistiocytosis: a single center retrospective study.","authors":"Meiling Liao, Li Xiao, Min Gu, Jie Yu","doi":"10.1007/s12026-026-09801-2","DOIUrl":"10.1007/s12026-026-09801-2","url":null,"abstract":"<p><strong>Background: </strong>Hemophagocytic lymphohistiocytosis (HLH) is a rare, highly fatal hyperinflammatory syndrome characterized by an uncontrolled cytokine cascade. Traditional chemotherapy leaves 30% of patients unresponsive, and its side effects are significant. Precise targeted therapies are highly anticipated. Emapalumab is a monoclonal antibody targeting interferon-γ, while ruxolitinib is a JAK1/2 inhibitor, and their application in HLH treatment is gaining attention.</p><p><strong>Methods: </strong>We retrospectively collected clinical data from pediatric HLH patients who received emapalumab added to conventional therapy, with or without ruxolitinib, at our hospital between June 1, 2022, and June 1, 2024. Treatment efficacy, safety, improvement in clinical parameters, and causes of death were analyzed.</p><p><strong>Results: </strong>A total of 10 pediatric patients were included: 7 with refractory disease, 2 with relapsed disease, and 1 with newly diagnosed disease. EBV-associated HLH was observed in 6 of the 10 patients. All patients received emapalumab added to conventional therapy, and 7 patients additionally received ruxolitinib. The median follow-up duration was 164 days (range, 19-473 days). Among the 10 patients, 5 achieved remission. The response rates for fever, hypofibrinogenemia, neutropenia, hyperbilirubinemia, and elevated transaminases were 6/6, 5/5, 8/9, 4/7, and 6/10, respectively. Among patients with relapsed/refractory disease, the remission rate was 2/3 with emapalumab plus conventional therapy alone and 2/6 with the further addition of ruxolitinib. In patients with non-EBV-associated HLH, the corresponding remission rates were 1/2 and 2/2, respectively. In patients with EBV-associated HLH, the rates were 1/1 and 1/5, respectively.</p><p><strong>Conclusions: </strong>In this small-sample retrospective study, emapalumab showed a more pronounced trend toward alleviating fever, hypofibrinogenemia, and neutropenia than toward improving liver function among pediatric HLH patients. Adding ruxolitinib to the combination of emapalumab and conventional therapy did not demonstrate a clear additional clinical benefit, particularly in the EBV-associated HLH and relapsed/refractory subgroups. These findings are constrained by the study design and sample size and necessitate validation in larger, prospective studies.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunological spectrum in patients with thymoma: beyond good syndrome.","authors":"Ezgi Sönmez, Fikriye Kalkan, Yasemin Balaban, Mustafa İlker İnan, Fevzi Demirel, Sait Yeşillik, Özgür Kartal","doi":"10.1007/s12026-026-09802-1","DOIUrl":"10.1007/s12026-026-09802-1","url":null,"abstract":"<p><p>Thymoma is associated with various immunological abnormalities, most notably Good syndrome; however, the full spectrum of immune dysfunction in these patients remains unclear. To evaluate the clinical and immunological characteristics of patients with thymoma and to identify occult immunodeficiency as well as associated autoimmune, infectious, and allergic conditions. In this retrospective single-center study, 37 adult patients with thymoma who had undergone thymectomy were evaluated at least one year after surgery. Clinical data, autoimmune and allergic comorbidities, infection history, and immunological parameters including immunoglobulin levels and lymphocyte subsets were analyzed. Good syndrome was identified in 2 patients (5.4%). However, additional immunological abnormalities were observed, including NK cell deficiency (16.2%), B cell lymphopenia (5.4%), isolated IgM deficiency (5.4%), and IgG subclass deficiency in 1 patient (2.7%). Recurrent infections were reported in 67.6% of patients. Autoimmune diseases were present in 86% and allergic diseases in 43.2% of patients. Patients with immunological abnormalities tended to have a higher frequency of recurrent infections. Our findings suggest that immune dysfunction in patients with thymoma may extend beyond classical Good syndrome and may involve a broader spectrum of immunological abnormalities. Systematic and long-term immunological evaluation may be important for the early detection and management of these conditions.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiome immune crosstalk in Sjögren's syndrome: mechanistic insights and translational perspectives.","authors":"Xiang-Yu Qi, Meng-Yuan Wang, Tian-Chi Wei, Fu-Biao Shao, Shu-Han Liu, Ding Han, Jing-Wen Cheng, Yun-He Zhao, Lei Shi, Jing Luo, Ting Cheng, Sheng-Xiao Zhang","doi":"10.1007/s12026-026-09800-3","DOIUrl":"10.1007/s12026-026-09800-3","url":null,"abstract":"<p><p>Sjögren's syndrome (SS) is a systemic autoimmune disorder driven by interactions among genetic susceptibility, environmental factors, and alterations in mucosal microbial ecosystems. Emerging evidence from studies of the gut, oral cavity, and ocular surface indicates that microbial dysbiosis is closely associated with SS. Patients frequently exhibit reduced beneficial commensals and expansion of potentially pathogenic taxa, accompanied by epithelial barrier disruption, imbalance of T helper 17 and regulatory T cells, abnormal B-cell responses, and sustained activation of type I interferon signaling. Several mechanisms may contribute to disease development, including molecular mimicry, exosome-mediated immune communication, and alterations in microbiota-derived metabolites. Integrated multi-omics approaches, particularly high-throughput sequencing and metabolomics, have revealed SS-associated microbial signatures and metabolic pathway changes, offering insights for biomarker discovery and therapeutic targeting. Microbiota-directed strategies, such as probiotic supplementation, fecal microbiota transplantation, and investigations of drug-microbiome interactions, have shown potential to restore immune homeostasis. However, current evidence remains limited by small cohort sizes, methodological heterogeneity, and insufficient clarification of causal relationships. This review summarizes microbial alterations in SS, their roles in immune dysregulation, and the therapeutic potential of microbiome-based interventions within the framework of personalized medicine.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune checkpoint inhibitor-induced myasthenia gravis and myocarditis: a fatal immune-related adverse event.","authors":"Whitney Main Allen, Mark Megaly, Pamrai Sharma","doi":"10.1007/s12026-026-09798-8","DOIUrl":"10.1007/s12026-026-09798-8","url":null,"abstract":"<p><p>Checkpoint inhibitors, a class of immunotherapeutic agents, have transformed the oncology landscape by targeting immune checkpoints - regulatory pathways that modulate immune cell activity. By inhibiting proteins such as programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), these agents enhance the immune response against cancer cells. However, their efficacy comes at the cost of a range of immune-related adverse events (irAEs), including autoimmune reactions such as colitis, hepatitis, and endocrinopathies, which can range in severity from mild to life-threatening. We present the case of a 76-year-old man with cholangiocarcinoma on durvalumab, a PD-L1 inhibitor, who presented to the emergency department with shortness of breath, cough, and weakness. Workup led to the diagnosis of immune-related myasthenia gravis and a non-ST-elevation myocardial infarction (NSTEMI), the latter believed to be secondary to durvalumab-induced myocarditis. Initial treatment with intravenous immunoglobulin (IVIG) produced brief, partial symptomatic improvement but failed to resolve respiratory weakness or other bulbar manifestations. His condition deteriorated rapidly, progressing to respiratory failure within weeks of onset. Given the refractory nature of his disease course, he was subsequently treated with a repeat dose of IVIG and prednisone, then transferred to an outside facility for plasma exchange. Despite these interventions, the patient ultimately succumbed to his illness. This case highlights the rare but potentially fatal concurrent occurrence of immune-related myasthenia gravis and myocarditis as irAEs in a patient receiving durvalumab for cholangiocarcinoma. While checkpoint inhibitors have revolutionized outcomes across many solid tumor malignancies, this case underscores the diagnostic and management challenges posed by severe, refractory irAEs, and the importance of early recognition and aggressive treatment in this patient population.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM28 and TRIM32: multifaceted regulators of innate immunity and antiviral defence.","authors":"Sreya Sherin Biju, Ravi Prakash Arya, Anismrita Lahon","doi":"10.1007/s12026-026-09799-7","DOIUrl":"10.1007/s12026-026-09799-7","url":null,"abstract":"<p><p>As versatile E3 ubiquitin ligases, Tripartite Motif (TRIM) proteins are essential elements of the innate immune response. The antiviral roles of TRIM28 and TRIM32 have been well documented, and they function in different ways. TRIM28 regulates the transcriptional expression of antiviral genes, while TRIM32 ubiquitinates host or viral proteins and directs their proteasomal breakdown. When taken together, they represent complementary transcriptional and post-translational host defence mechanisms. While TRIM28 primarily acts as a transcriptional repressor and TRIM32 as an E3 ubiquitin ligase, both proteins also play opposing roles in cell differentiation and immunity. Given the large number of TRIM family members, focusing on these two allows us to present representative transcriptional and ubiquitination-mediated regulatory mechanisms in depth. This review focuses on the regulatory differences in TRIM28 and TRIM32 in RIG-like receptor (RLR) signalling, Stimulator of Interferon Genes (STING) pathways, Toll-like receptor (TLR) signalling, and NOD-like receptors (NLR)-mediated inflammation, which are key to the host's immune response. These protein interactomes exhibit a significant interaction with other cellular pathways, broadening their significance beyond antiviral responses to encompass broader genetic and therapeutic implications.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding PANoptosis: Crosstalk of cell death pathways in immunity and inflammation.","authors":"K Subashree, Kannan Harithpriya, Goutham V Ganesh, Kunka Mohanram Ramkumar","doi":"10.1007/s12026-026-09796-w","DOIUrl":"10.1007/s12026-026-09796-w","url":null,"abstract":"<p><p>PANoptosis is an emerging regulated cell death that integrates the molecular machinery of apoptosis, necroptosis, and pyroptosis into a combined, highly coordinated process. Defined as a distinct, integrative form of cell death, PANoptosis simultaneously engages these three pathways through a multiprotein scaffold known as the PANoptosome, ensuring robust elimination of infected, damaged, or transformed cells. Initially described in response to viral infections, PANoptosis is now recognized as a critical regulator of immune defense, inflammation, and tissue homeostasis, with broad implications for infectious diseases, cancer, autoimmune disorders, neurodegeneration, and ischemia-reperfusion injury. This review provides a comprehensive overview of the molecular composition of the PANoptosome, key triggers of PANoptosis, and its morphological and biochemical hallmarks. We further discuss its dual roles as both a protective and pathogenic mechanism, highlighting context-dependent contributions to host defense and disease progression. Finally, we examine therapeutic opportunities, including small-molecule inhibitors and gene-editing approaches, and outline current challenges, such as the identification of reliable biomarkers and the need for precision-targeted strategies. By integrating recent advances, this review highlights PANoptosis as a conceptual shift in cell death biology and a promising avenue for novel interventions in inflammation-driven diseases.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on \"Anti-neutrophil cytoplasmic antibodies in interstitial lung disease: results from a cross-sectional study and meta-analysis\".","authors":"Shaheer Tahir, Zoha Chaudhary, Noor Un Nisa","doi":"10.1007/s12026-026-09797-9","DOIUrl":"https://doi.org/10.1007/s12026-026-09797-9","url":null,"abstract":"","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between COVID-19 booster vaccination and influenza mortality: a nationwide retrospective cohort study using the SIVEP-Gripe database in Brazil.","authors":"Daniele Melo Sardinha, Natália Melazo Machado Neves, Tamires de Nazaré Soares, Marcos Jessé Abrahão Silva, Lidiane Assunção de Vasconcelos, Luany Rafaele da Conceição Cruz, Karina Faine Freitas Takeda, Natasha Cristina Oliveira Andrade, Suziane do Socorro Dos Santos, Felipe Costa Soares, Neiva José da Luz Dias Júnior, Yan Corrêa Rodrigues, Ilma Pastana Ferreira, Mônica Custódia do Couto Abreu Pamplona, Ivonete Vieira Pereira Peixoto, Luana Nepomuceno Gondim Costa Lima","doi":"10.1007/s12026-026-09792-0","DOIUrl":"10.1007/s12026-026-09792-0","url":null,"abstract":"<p><p>To identify clinical and epidemiological predictors of mortality among patients hospitalized with laboratory-confirmed influenza in Brazil during 2024, and to evaluate the association of vaccination and antiviral therapy with clinical outcomes. We conducted a nationwide retrospective cohort study using the Brazilian SIVEP-Gripe surveillance database. All hospitalized patients with RT-PCR-confirmed influenza and known outcomes were included. Multivariable logistic regression was initially performed to explore predictors of mortality. To more rigorously assess the association between COVID-19 booster vaccination and mortality, a propensity score-based inverse probability of treatment weighting (IPTW) approach was applied, with weights truncated at 10. E-values were calculated to assess robustness to unmeasured confounding. A total of 15,995 hospitalized influenza cases were included, with an overall case fatality rate of 12.1%. Influenza A predominated (88.0%) and was associated with higher mortality than Influenza B. In IPTW-weighted models, COVID-19 booster vaccination remained independently associated with reduced mortality (OR 0.90, 95% CI 0.84-0.97; p = 0.007). Additional risk factors included dyspnea, respiratory distress, and low oxygen saturation, as well as comorbidities such as obesity, diabetes, liver disease, and immunosuppression. Protective factors included influenza vaccination (OR 0.77) and oseltamivir use (OR 0.81). The model demonstrated good discrimination (AUC = 0.81, 95% CI 0.80-0.82). The E-value for the booster association was 1.46, indicating moderate robustness to unmeasured confounding. Influenza mortality in Brazil is primarily driven by age, comorbidities, and clinical severity at presentation, but is significantly mitigated by vaccination and antiviral therapy. The observed association between COVID-19 booster vaccination and reduced mortality suggests a possible heterologous immune effect, although causality cannot be established. These findings support integrated immunization strategies targeting multiple respiratory pathogens.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13284014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294801","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}