BMC Immunol
· 2026 Apr · PMID 41942860
·
Full text
BACKGROUND: Endometrial cancer (EC) is a heterogeneous gynecologic malignancy with distinct histological subtypes and diverse etiological factors. While autoimmune diseases have been associated with cancer development, t...BACKGROUND: Endometrial cancer (EC) is a heterogeneous gynecologic malignancy with distinct histological subtypes and diverse etiological factors. While autoimmune diseases have been associated with cancer development, the causal relationship between Sjögren’s syndrome (SS) and EC remains unclear. In this study, we employed a Mendelian randomization (MR) approach to investigate this complex association. METHODS: We conducted a two-sample MR study using genome-wide association study summary statistics from European ancestry cohorts. Genetic instruments for SS were derived from the FinnGen consortium, and outcome data for EC, including its endometrioid and non-endometrioid subtypes, were obtained from a large-scale EC meta-analysis. Multiple MR methods and sensitivity analyses were applied to assess robustness and detect pleiotropy. RESULTS: Genetically predicted SS was causally associated with an increased risk of overall EC (OR = 1.1480, 95% CI: 1.0511–1.2537, P = 0.0155), particularly endometrioid EC (OR = 1.1603, 95% CI: 1.0442–1.2894, P = 0.0207). No causal association was observed with non-endometrioid EC (OR = 1.0844, 95% CI: 0.8018–1.4665, P = 0.4560). Sensitivity analyses revealed no significant heterogeneity or horizontal pleiotropy, supporting the robustness of the findings. CONCLUSIONS: This MR study provides genetic evidence for a causal relationship between SS and increased risk of endometrioid EC, but not non-endometrioid EC. These findings suggest subtype-specific immune mechanisms underlying EC development and may inform targeted screening strategies for women with SS. Future research should explore the immuno-hormonal pathways linking autoimmunity and endometrial carcinogenesis.
BMC Immunol
· 2026 Apr · PMID 41928099
·
Full text
OBJECTIVE: The incidence of pet allergies continues to rise. This study investigates the clinical distribution characteristics and changes of cat and dog dander allergens among all outpatients and inpatients treated at H...OBJECTIVE: The incidence of pet allergies continues to rise. This study investigates the clinical distribution characteristics and changes of cat and dog dander allergens among all outpatients and inpatients treated at Hangzhou First People’s Hospital from 2016 to 2024. It aims to provide data support for clinical allergen screening, individualized avoidance strategies, and precision diagnosis and treatment. METHODS: A retrospective cohort study was conducted. All outpatients and inpatients who underwent serum allergen-specific IgE (sIgE) antibody testing at Hangzhou First People’s Hospital from January 2016 to December 2024 were retrospectively included. The study analyzed each test individually, repeated tests performed at different time points for the same patient were included in the analysis. The characteristics and trends of cat and dog dander allergens were analyzed over a nearly 9-year period, encompassing a total of 141,165 test instances. Male cases numbered 70,904 (50.23%), while female cases numbered 70,261 (49.77%). Patients were categorized by age group: 0–3 years (infant group, 6,729 cases, 4.76%), 4–12 years (child group), 13–18 years (adolescent group), 19–65 years (adult group), and > 65 years (elderly group). This yielded 20,197 cases (14.31%) in the infant group, 55,280 cases (39.16%) in the child group, 6,729 cases (4.76%) in the adolescent group, 54,345 cases (38.50%) in the adult group, and 4,613 cases (3.27%) in the elderly group. Statistical analysis employed the χ² test. RESULTS: Among 141,165 test results, the sIgE positivity rate for cat dander allergen (3.76%) was higher than that for dog dander allergen (3.38%), with a statistically significant difference (χ²=11680.12, P < 0.001). The positive rates for cat dander sIgE from 2016 to 2024 were 1.45%, 0.64%, 0.66%, 1.74%, 2.54%, 4.37%, 5.66%, 6.74%, and 9.36%, respectively. The positive rates for dog dander allergen sIgE sensitization from 2016 to 2024 were 0.57%, 0.16%, 0.09%, 0.25%, 0.50%, 3.30%, 5.77%, 7.09%, and 11.48%, respectively; Since 2018, the positive rates for cat and dog dander allergen sIgE have shown a significant upward trend over time in both males and females. The positive rates for cat and dog dander allergen sIgE were consistently higher in males than in females, with statistically significant differences (χ² = 11.922, χ² = 67.499, p < 0.05). The positive rates for cat dander allergens (3.94%, 3.59%) were significantly higher than those for dog dander allergens (3.78%, 2.99%) in both males and females, with statistically significant differences (χ²=5121.29, χ²=6755.70, P < 0.001); The positive rates for cat dander allergens in the infant/child group (2.30%) and elderly group (0.59%) were significantly lower than those for dog dander allergens (4.05%, 0.89%), with both differences being statistically significant (χ²=615.55, χ²=55.43, P < 0.001); The positive rates for cat dander allergens in the children, adolescents, and adults groups (4.78%, 6.54%, 3.18%) were significantly higher than the dog dander allergen positive rates (4.75%, 4.64%, 1.81%), with all differences being statistically significant (χ²=2429.89, χ²=369.45, χ²=1191.82, P<0.001); The concordance rate for cat and dog dander allergies was 68.06%, with moderate correlations observed between sIgE levels for these allergens. When only one allergen showed positive sIgE, most positive results were low-level (levels 1–3); however, combined high-level positives also occurred. CONCLUSION: This study reveals the epidemiological characteristics of cat and dog dander allergens in Hangzhou over the past nine years, revealing patterns of overall increase, gender differences, and age clustering. These findings provide crucial data support for optimizing clinical allergen screening strategies, developing personalized avoidance plans, and advancing precision diagnosis and treatment.
Youssry S, Ghoneim H, Ammar Y
… +2 more, Magdy A, Maharem D
BMC Immunol
· 2026 Mar · PMID 41917814
·
Full text
BACKGROUND: Inflammation and alteration of the immune system play a key role in the pathogenesis of diabetes mellitus (DM). However, little is known about the underlying mechanisms involved in the inflammatory pathways o...BACKGROUND: Inflammation and alteration of the immune system play a key role in the pathogenesis of diabetes mellitus (DM). However, little is known about the underlying mechanisms involved in the inflammatory pathways of diabetic kidney disease (DKD). We aimed in this study to evaluate immunoglobulin A (IgA) subclasses/ratio and B cell lymphoma-6 (BCL-6) in relation to inflammasome adaptor protein ASC (apoptosis-associated speck-like protein containing a caspase activation and recruiting domain) in diabetic patients with and without kidney disease. The present study was conducted on 50 diabetic patients who were classified into 25 patients without kidney disease and 25 DKD patients, together with 25 age-matched healthy individuals. Enzyme-linked immunosorbent assay (ELISA) was used to assess ASC and BCL-6 levels in culture supernatants of peripheral blood mononuclear cells as well as to determine IgA1 and IgA2 levels in individuals' serum. RESULTS: The results revealed a significant increase in ASC levels together with a significant decrease in IgA1 and BCL-6 levels in DKD patients compared to other groups. A significant association was observed between the IgA1/ IgA2 ratio and improved disease markers in all patients. In addition, ASC levels were negatively correlated with both IgA2 and BCL-6 levels. CONCLUSIONS: It can be concluded that altered IgA subtypes and its ratio (IgA1/IgA2) as well as BCL-6 may be involved in the pathogenesis of DKD, suggesting their future therapeutic potential in DKD patients.
Kashyap H, Rathi B, Singh H
… +3 more, Kaur N, Sharda S, Sharma AK
BMC Immunol
· 2026 Mar · PMID 41888661
·
Full text
BACKGROUND: Gastrointestinal adenocarcinomas are a major cause of mortality globally, underpinning the desire for new approaches to immunotherapeutic strategies. SEPT9 is clinically validated as an FDA-approved colorecta...BACKGROUND: Gastrointestinal adenocarcinomas are a major cause of mortality globally, underpinning the desire for new approaches to immunotherapeutic strategies. SEPT9 is clinically validated as an FDA-approved colorectal cancer biomarker, suggesting its potential as a candidate antigen for vaccine development. METHODS: An immunoinformatic pipeline created a multi-epitope chimera vaccination using strict standards of high antigenicity, non-allergenicity, non-toxicity, and worldwide population coverage. Five epitopes (three MHC-I and two MHC-II) were ranked from SEPT9. Selected epitopes were concatenated with suitable linkers for MHC-I and MHC-II, connected to a human β-defensin adjuvant. The construct composed of 134 amino acids was built using the trRosetta algorithm, refined using the GalaxyRefine2.0 algorithm, and validate via PROCHECK, ERRAT and ProSA. Immune response prediction was conducted by performing docking studies against TLR2 and TLR4 (via ClusPro software), and performing C-ImmSim immune simulations. RESULTS: The designed construct demonstrated predicted favorable physicochemical properties (solubility: 0.89), safety, and immunogenicity potential in silico. Docking ΔG values (TLR2: –17.7 kcal/mol; TLR4: –23.9 kcal/mol) and immune simulation data indicated theoretical potential to trigger innate and adaptive immunity. CONCLUSION: The SEPT9-based multi-epitope vaccine construct demonstrated promising predicted immunogenic and structural properties in silico. However, these findings are computational and hypothesis-generating; experimental validation is required to assess immunogenicity, safety, and therapeutic efficacy in biological systems.
Lu S, Huang F, Zhang Q
… +4 more, Yang X, Sun H, Ji C, Long G
BMC Immunol
· 2026 Mar · PMID 41882536
·
Full text
BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by acute diffuse lung injury, with pulmonary fibrosis (PF) being a significant complication. The expression patterns and functional role of miR-548a...BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by acute diffuse lung injury, with pulmonary fibrosis (PF) being a significant complication. The expression patterns and functional role of miR-548a-3p in ARDS and associated PF remain unexplored. PURPOSE: This study aims to delineate the diagnostic and prognostic significance of miR-548a-3p in ARDS and elucidate its underlying molecular mechanisms. METHODS: Serum miR-548a-3p levels in ARDS patients were quantified using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Diagnostic value was evaluated via receiver operating characteristic (ROC) curves and binary logistic regression, and prognostic significance via Kaplan-Meier analysis and Cox regression. Interleukin-6 (IL-6)/Interleukin-8 (IL-8) levels were measured via enzyme-linked immunosorbent assay (ELISA). Potential targets were screened (NCBI/miRDB) and binding validated by dual-luciferase reporter assays. In lipopolysaccharide (LPS)-injured BEAS-2B cells, miR-548a-3p/Oncostatin M (OSM) regulation effects were examined via ELISA, Cell Counting kit-8 (CCK-8), and flow cytometry. RESULTS: ARDS patients exhibited decreased miR-548a-3p expression, which correlated negatively with IL-6 and IL-8. Furthermore, miR-548a-3p effectively discriminated between ARDS patients and healthy individuals and served as a predictor of ARDS. In LPS-injured BEAS-2B cells, miR-548a-3p overexpression promoted proliferation, suppressed apoptosis, and reduced inflammation. OSM was identified as a direct target of miR-548a-3p through database screening and experimental validation. OSM overexpression reversed the protective effects of miR-548a-3p on LPS-injured lung epithelial cells. CONCLUSIONS: This study is the first to reveal that miR-548a-3p exerts protective effects in ARDS by targeting OSM, underscoring its great potential as a novel diagnostic and prognostic biomarker.
Peripheral T cell lymphomas (PTCLs) are a diverse group of aggressive malignancies that arise from mature, post-thymic T cells. Recent genomic and mechanistic studies reveal that these cancers frequently 'hijack' signall...Peripheral T cell lymphomas (PTCLs) are a diverse group of aggressive malignancies that arise from mature, post-thymic T cells. Recent genomic and mechanistic studies reveal that these cancers frequently 'hijack' signalling pathways that normally govern T cell activation at the immunological synapse. Specifically, numerous gain-of-function alterations in TCR proximal regulators and mediators of antigen-induced NF-κB activation, as well as mutations or overexpression of co-stimulatory receptors and dysregulated cytokine receptor signalling, promote the constitutive proliferation and survival of malignant clones. Conversely, loss-of-function mutations in PDCD1 or disruption of PD1-mediated inhibitory control, coupled with altered metabolic and epigenetic reprogramming, have emerged as a major tumour-suppressor mechanism in PTCL pathogenesis. This framework conceptualizes PTCLs as 'cancers of aberrant immune synapse signalling pathways' and posits that genetic dissection of PTCL pathogenesis can uncover fundamental aspects of T cell biology to guide the design of safer, more effective next-generation T cell therapies.
BMC Immunol
· 2026 Mar · PMID 41877003
·
Full text
BACKGROUND: High mortality of pediatric acute respiratory distress syndrome (PARDS) demands new biomarkers. AIM: The study aims to clarify the clinical value of miR-192-5p in PARDS and its regulatory role in inflammatory...BACKGROUND: High mortality of pediatric acute respiratory distress syndrome (PARDS) demands new biomarkers. AIM: The study aims to clarify the clinical value of miR-192-5p in PARDS and its regulatory role in inflammatory responses. METHODS: Baseline data and serum samples were collected from healthy children, sepsis children, and sepsis-induced PARDS subjects. The receiver operating characteristic curve (ROC), Kaplan-Meier curve and multivariate Cox regression were used to assess miR-192-5p’s diagnostic and prognostic value for PARDS. The relationship between miR-192-5p and each index was evaluated by correlation analysis. The expression of miR-192-5p, inflammatory factors and ZEB2 in the subjects’ serum and human pulmonary microvascular endothelial cells (HPMECs) were detected by RT-qPCR. The cell viability and secretion of inflammatory factors were evaluated by CCK-8 and ELISA kit. Bioinformatic prediction combined with dual-luciferase reporter assay was used to verify the target genes. RESULTS: miR-192-5p was significantly low-expressed in PARDS patients’ serum. MiR-192-5p was a prognostic protective factor for PARDS, and low miR-192-5p indicated poor prognosis. MiR-192-5p was negatively correlated with TNF-α, IL-6, IL-1β, and APACHE II score. LPS treatment led to reduced HPMECs viability, excessive inflammatory factor production, and down-regulated miR-192-5p expression. Overexpression of miR-192-5p mimic could partially reverse the above phenomena, while knockdown could aggravate the above phenomena. ZEB2 was a downstream target gene of miR-192-5p. CONCLUSIONS: miR-192-5p serves as a diagnostic biomarker for PARDS and links to poor prognosis. Downregulation of miR-192-5p may promote LPS-induced inflammatory response and induce HPMECs cell viability by targeting ZEB2, thereby involving in the progression of PARDS.
Matsuda KM, Kawase Y, Iwadoh K
… +27 more, Kurano M, Yatomi Y, Okamoto K, Moriya K, Kotani H, Hisamoto T, Kuzumi A, Fukasawa T, Yoshizaki-Ogawa A, Kono M, Okamura T, Shoda H, Fujio K, Yamaguchi K, Okumura T, Ono C, Kobayashi Y, Sato A, Miya A, Uchino R, Murakami Y, Matsunaka H, Imai H, Sato S, Raymond R, Yoshizaki A, Goshima N
BMC Immunol
· 2026 Mar · PMID 41864890
·
Full text
UNLABELLED: This study presents “aUToAntiBody Comprehensive Database (UT-ABCD)”, a comprehensive catalog of autoantibody profiles in 284 human individuals. The subjects include patients diagnosed with Coronavirus disease...UNLABELLED: This study presents “aUToAntiBody Comprehensive Database (UT-ABCD)”, a comprehensive catalog of autoantibody profiles in 284 human individuals. The subjects include patients diagnosed with Coronavirus disease 2019 (COVID-19; = 73), systemic sclerosis (SSc; = 32), systemic lupus erythematosus (SLE; = 60), anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV; = 29), atopic dermatitis (AD; = 26), as well as healthy controls (HC; = 64). Our investigation employs proteome-wide autoantibody screening (PWAbS) that utilizes 13,352 autoantigens displayed on wet protein arrays (WPAs). Our WPAs display human proteins synthesized in vitro utilizing a wheat germ cell-free system, maintained in a hydrated state. Our findings demonstrated significant increases in the number of IgG autoantibodies in COVID-19, SSc, SLE, AAV, and AD compared to HCs, whereas the sum of IgG autoantibody levels was significantly higher in COVID-19, SSc, and SLE. Employing machine learning, we distinguished COVID-19 cases with high accuracy based on autoantibody profiles, notably identifying antibodies against proteins encoded by and as highly specific to COVID-19 (specificity: 87% and 97%, respectively). Our research highlights the effectiveness of integrating PWAbS and autoantigenomics in exploring immune responses in COVID-19 and other diseases. Although external validation and functional assays were not performed, the identified reactivities represent serological biomarkers and immune signatures associated with COVID-19 and provide a comprehensive resource for future biomarker discovery. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12865-026-00826-8.
Macrophages orchestrate inflammation, tissue repair and tumour surveillance, yet macrophage-targeted strategies such as CSF1R inhibition, CD47 blockade or TLR7/8 agonists have so far yielded only modest, context-restrict...Macrophages orchestrate inflammation, tissue repair and tumour surveillance, yet macrophage-targeted strategies such as CSF1R inhibition, CD47 blockade or TLR7/8 agonists have so far yielded only modest, context-restricted benefit. The C-type lectin CLEC10A (MGL/CD301) recognises a single terminal α-N-acetylgalactosamine (α-GalNAc) and couples this minimalist glycan cue to context-dependent inflammatory or reparative programmes, making it an attractive target for precision macrophage re-programming. This review synthesises mechanistic, pre-clinical and clinical data on Gc protein-derived macrophage-activating factor 2.0 (GcMAF2.0), a mono-α-GalNAc derivative of vitamin-D-binding protein that engages CLEC10A with high avidity. We summarise lessons from heterogeneous "GcMAF1.0" products, outline GMP workflows that yield EF-M1/EF-M2, and review CLEC10A-centred signalling and metabolic re-wiring, including SYK versus STAT6/PPARγ cascades and shifts in arginine, glucose and fatty-acid metabolism. Cross-species data from rodent inflammation models, human and canine myeloid cells, barrier-tissue and tumour models, and mesoscopic platforms indicate that α-GalNAc ligands and EF-M2 bias macrophage profiles and attenuate joint and barrier-tissue inflammation. A randomised double-blind placebo-controlled trial of EF-M2 in canine osteoarthritis links macrophage repolarisation to pain relief, gait restoration and serum ARG1/iNOS and IL-10/TNF-α shifts, providing disease-modifying proof of concept. We also review the small, uncontrolled human experience with analytically characterised GcMAF2.0 (≈120 patient-courses), noting favourable short-term tolerability but low certainty of benefit and a need for randomised, lot-traceable trials with mechanistic endpoints. Overall, we position the α-GalNAc-CLEC10A axis as a tunable handle on macrophage plasticity and outline the experimental and regulatory priorities needed to translate GcMAF2.0 into evidence-based immunotherapy.
BMC Immunol
· 2026 Mar · PMID 41851615
·
Full text
BACKGROUND: Gouty arthritis (GA) is caused by hyperuricemia and the articular deposition of urate crystals, for which current treatments remain suboptimal. Considering the anti-inflammatory properties of Dendrobium extra...BACKGROUND: Gouty arthritis (GA) is caused by hyperuricemia and the articular deposition of urate crystals, for which current treatments remain suboptimal. Considering the anti-inflammatory properties of Dendrobium extracts, especially Dendrophenol (Den), this study conducted an in-depth investigation into its effects on GA. METHODS: Through methylthiazolyldiphenyl-tetrazolium bromide (MTT) test, the impact of Den on bone marrow-derived primary macrophages (BMDMs) was assessed to ascertain its non-toxic dosage range. The GA cell model was established, subjected to Den (0.5 µM) treatment, and transfected with leucine rich repeat kinase 1 (LRRK1) overexpression plasmid, after which the pyroptosis and inflammatory indices were detected. Bioinformatics was applied to examine GA-associated target genes and LRRK1 interaction targets. Cells with phosphoinositide-3-kinase adaptor protein 1 (PIK3AP1) knockdown were generated to determine the mechanism by which Den improves GA. RESULTS: 0.5 µM Den significantly inhibited the expression of LRRK1 in GA cells, and down-regulated the pyroptosis level of cells and the contents of inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Overexpression of LRRK1 reversed these regulatory effects of Den. Bioinformatics analysis determined that PIK3AP1 was the downstream target of LRRK1. Den intervention reduced PIK3AP1 mRNA levels, and PIK3AP1 knockdown attenuated the effects of LRRK1 overexpression on pyroptosis and inflammatory factors. CONCLUSION: In our in vitro model, Den inhibits inflammation and pyroptosis by regulating the LRRK1/PIK3AP1 signaling pathway, highlighting this axis as a promising novel target for GA treatment. CLINICAL TRIAL NUMBER: Not applicable.
Over the past 20 years, the limited efficacy of CD8⁺ T cell-based vaccines against viruses in clinical trials has shifted attention away from such strategies. However, recent findings have brought renewed appreciation fo...Over the past 20 years, the limited efficacy of CD8⁺ T cell-based vaccines against viruses in clinical trials has shifted attention away from such strategies. However, recent findings have brought renewed appreciation for the central importance of CD8⁺ T cells in controlling both acute and chronic viral infections and in preventing severe or progressive disease. This work highlights shared features, such as effector functions and stemness properties, of effective CD8⁺ T cell responses against diverse viruses such as SARS-CoV-2 and HIV. A deeper understanding and simpler interpretation of the functional workings of CD8⁺ T cell-mediated immunity, combined with advances in immunological and biotechnological tools, are opening new avenues for eliciting optimal T cell responses, both for prophylactic and for therapeutic applications. Collectively, these developments revive optimism that vaccines and immunotherapies designed to harness robust CD8⁺ T cell responses could have a major role in combating emerging viral threats and in achieving long-term suppression of persistent infections such as HIV-1 to undetectable levels.
The function of innate immune sensors is intricately shaped by their spatial distribution within cells. cGAS (cyclic GMP-AMP synthase), a key cytosolic DNA sensor, illustrates this principle through its unexpected locali...The function of innate immune sensors is intricately shaped by their spatial distribution within cells. cGAS (cyclic GMP-AMP synthase), a key cytosolic DNA sensor, illustrates this principle through its unexpected localisation to diverse organelles-including the nucleus, micronuclei, mitochondria, and plasma membrane. In these compartments, cGAS assumes distinct regulatory states and executes specialised functions. For instance, chromatin-bound nuclear cGAS remains inactive under homeostasis but contributes to genome maintenance during genotoxic stress, whereas mitochondrial or micronuclear cGAS links damage signals to inflammation and cell death. This review synthesises recent advances in the spatial regulation of cGAS, focusing on mechanisms such as membrane interactions and post-translational modifications. We further reframe cGAS as a multifunctional regulator in infection, cancer, autoimmunity, and ageing, and introduce a unifying 'location code' framework. This framework proposes that the combined influence of PTMs, protein interactions, and membrane affinities dictates cGAS localisation, functional output, and pathological outcomes, thereby paving the way for spatially informed therapeutic interventions.
Biraro IA, Sitenda D, Ssekamatte P
… +11 more, Matovu S, Kasule V, Nakavuma R, Nakibuule M, Kyazze AP, Nabatanzi R, Kibirige D, Nakimuli A, Bongomin F, Baluku JB, Cose S
BMC Immunol
· 2026 Mar · PMID 41840476
·
Full text
BACKGROUND: Maternal tuberculosis (TB) remains a significant risk factor for compromising infant immune development in high-burden TB disease settings. The integrity of B-cells in early life is important for the developm...BACKGROUND: Maternal tuberculosis (TB) remains a significant risk factor for compromising infant immune development in high-burden TB disease settings. The integrity of B-cells in early life is important for the development of immediate and long-term immunity in infants. This study assessed circulating B-cell subset frequencies in babies born to mothers with and without active TB in Uganda. METHODS: A cohort of 46 mother-infant pairs (24 cases, 22 controls) was recruited between September 2021 and July 2022 from three health facilities in Kampala. Infant cases were born to mothers with active TB, whereas infant controls were born to mothers without active TB. Peripheral blood mononuclear cells (PBMCs) were collected and processed from infants at baseline (≤ 1 month of age), and at three months and six months. PBMCs were stained with a 15-marker B-cell panel for spectral flow cytometry. Data were analysed using FlowJo and R v4.4.3. Mixed-effects modelling was applied for statistical testing, with time point as a fixed effect and participant as a random effect. Post-hoc comparisons used estimated marginal means. RESULTS: At baseline, infant cases were associated with decreased mean circulating frequencies of total B cells (18.5 versus 30.2; p = 0.02), naïve B cells (55.1 versus 68.9; p = 0.01), and mature B cells (43.6 versus 66.5; p = 0.03) compared to infant controls. Additionally, the infant cases were associated with increased baseline immature (56.4 versus 33.4; p = 0.03) and antibody-secreting B cells (15.6 versus 10.5; p = 0.04) compared to infant controls. No differences were observed at three or six months, except for IgG-only memory B cells, which were increased among infant cases at six months (14.4 versus 8.3; p = 0.04). CONCLUSIONS: Exposure to Mycobacterium tuberculosis in utero may decrease the preimmune B-cell repertoire in early life, potentially increasing the risk of neonatal infections and altered responses to routine infant vaccines. Prompt diagnosis and treatment of TB during pregnancy are therefore crucial to prevent poor neonatal morbidity and mortality in our setting.
Yamazaki T, Minami A, Kitagawa K
… +3 more, Yanase S, Ueki H, Shirakawa T
BMC Immunol
· 2026 Mar · PMID 41840469
·
Full text
BACKGROUND: Immune checkpoint inhibitors (ICI) have improved outcomes in mismatch repair–deficient/microsatellite instability–high colorectal cancer (CRC), yet only a subset of patients achieve durable benefit. The gut m...BACKGROUND: Immune checkpoint inhibitors (ICI) have improved outcomes in mismatch repair–deficient/microsatellite instability–high colorectal cancer (CRC), yet only a subset of patients achieve durable benefit. The gut microbiota, particularly Enterococcus species, can modulate antitumor immunity and influence ICI efficacy. We investigated the probiotic potential of Enterococcus faecalis KU-EF-004, a non-antibiotic-resistant urinary isolate, as an adjunct to enhance ICI therapy in CRC. METHODS: MC38 tumor-bearing C57BL/6J mice received combination therapy with KU-EF-004 and anti-PD-1 or anti-CTLA-4 antibodies, and the therapeutic efficacy was compared with E. faecalis ATCC700802 strain and PBS-treated groups. Additionally, combination therapy with KU-EF-004 and either anti-PD-1 or anti-CTLA-4 antibodies was performed to evaluate which immune checkpoint inhibitor was associated with enhanced therapeutic effects. Dendritic cell activation in Peyer’s patches was assessed by flow cytometry, and gut microbiota changes were analyzed using 16S rRNA gene sequencing. RESULTS: KU-EF-004 markedly enhanced anti–CTLA-4 efficacy, reducing tumor growth and prolonging survival, whereas no benefit was observed with anti–PD-1. KU-EF-004 promoted dendritic cell activation and upregulated immune markers (CD80, CD86, IFN-γ, MHC II, IL-6, CD8a) in Peyer’s patches. 16S rRNA sequencing revealed increased microbial diversity and enrichment of Lactobacillus species following combined KU-EF-004 and anti–CTLA-4 treatment. CONCLUSION: These findings identify E. faecalis KU-EF-004 as a promising probiotic candidate to augment immune checkpoint blockade efficacy in colorectal cancer.