BMC Immunology最新文献

{"title":"G protein-coupled receptor autoantibody expression patterns in adults with decelerated biological aging mirror pediatric profiles.","authors":"Krystallenia Paniskaki, Ulrik Stervbo, Sarah Goretzki, Doreen Hufnagel, Moritz Anft, Harald Heidecke, Timm H Westhoff, Hana Rohn, Ursula Felderhoff-Mueser, Oliver Witzke, Christian Dohna-Schwake, Nina Babel","doi":"10.1186/s12865-026-00862-4","DOIUrl":"10.1186/s12865-026-00862-4","url":null,"abstract":"<p><strong>Background: </strong>G protein-coupled receptors (GPCRs) represent the largest and most diverse family of membrane proteins. In addition to their endogenous ligands, functional natural autoantibodies (Aab) have also been shown to bind and modulate GPCRs. Aab concentration is known to increase with chronological age, and several studies demonstrated an association of certain GPCR-binding Aab with chronic inflammation, concretely with specific autoimmune diseases in adults. However, prevalence of GPCR-Aab in pediatric population is not known so far.</p><p><strong>Methods: </strong>In this descriptive study, we investigated the levels of Aab targeting 14 distinct GPCRs across individuals (pediatric, n = 83, adults n = 198) taking into consideration chronological and biological age, as defined by PhenoAge clock.</p><p><strong>Results: </strong>Our findings suggest, that anti-GPCR Aab are present from childhood through adulthood; however, their expression patterns undergo significant changes over the course of life. Specifically, we observed a significant increase in Aab targeting ACE2, CXCR3, and BDKRB1 in adults and older individuals. Conversely, concentrations of Aab against ATR1, ADRA1A, ADRB2, and ETAR were significantly higher in children compared to adults. We also assessed the impact of age acceleration on Aab levels, defined by a positive Δ age score based on the PhenoAge clock. Distinct GPCR Aab expression signatures correlated with accelerated aging, differing notably from patterns seen in pediatric and adult cohorts. Concretely, the expression profile of GPCR Aab in -Δage adults exhibits similarity to that observed in the pediatric cohort. Furthermore, we found a concordant presence of CXCR3-Aab and expansion of CXCR3 + T cells with increased chronological age.</p><p><strong>Conclusions: </strong>Because systemic chronic inflammation is a known driver of accelerated aging, we hypothesize that the altered Aab expression profiles observed in biologically older adults may reflect this underlying inflammatory state. Although future research will be essential to evaluate the therapeutic potential of targeting these GPCRs in the context of inflammaging and autoimmune pathophysiology, chronological as well as biological age should be considered when assessing GPCR-Aab patterns.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"27 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13235001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155286","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":"Thyroid nodule and autoimmune thyroid disease frequency in adults with inborn errors of immunity: a case-control study.","authors":"Zeliha Yarar, Mehmet Emin Gerek, Fatih Çölkesen, Şevket Arslan, Feridun Karakurt","doi":"10.1186/s12865-026-00863-3","DOIUrl":"10.1186/s12865-026-00863-3","url":null,"abstract":"<p><strong>Background: </strong>Inborn errors of immunity (IEIs) are defined by impaired immune function and abnormal immune system development. The recognition of significant interactions between the immune and endocrine systems has emerged as an area of growing clinical interest. The study aimed to evaluate the frequency of thyroid nodules and autoimmune thyroid diseases in patients with IEIs.</p><p><strong>Materials and methods: </strong>This study included 40 IEI patients and 65 healthy subjects as control group. Demographic and clinical data were collected from medical records. All participants underwent thyroid ultrasound and biochemical evaluation for thyroid function tests and autoantibody levels. The diagnosis of autoimmune thyroid disease (AITD) diagnosis was based on thyroid specific autoantibody levels, thyroid function tests, and/or ultrasonographic features consistent with thyroiditis.</p><p><strong>Results: </strong>Thyroid nodules were detected in 5 patients (12.5%) in the IEI group and in 14 subjects (21.5%) in the control group, with no statistically significant difference in thyroid nodule frequency between the two groups (p = 0.243). AITD was significantly more prevalent in the IEI group compared to controls (45.0% vs. 23.1%; p = 0.019). Mean total thyroid volume was significantly smaller in IEI patients than in controls (6.85 ± 2.92 mL vs. 10.52 ± 5.44 mL; p < 0.05).</p><p><strong>Conclusions: </strong>Our findings demonstrated that AITD is significantly more prevalent in IEI patients. Thyroid nodule frequency did not differ between groups. These findings support the routine incorporation of thyroid ultrasonography and autoantibody screening into IEI follow-up protocols. Larger multicenter prospective studies are warranted to confirm these observations across diverse IEI subtypes.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101027","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 LncRNA MIAT acts as a sponge for miR-942-5p to exacerbate the inflammation and oxidative stress in macrophages during sepsis-associated liver injury.","authors":"Juanjuan Shi, Zhiyuan Liu, Juan Liu, Enming Shi","doi":"10.1186/s12865-026-00860-6","DOIUrl":"10.1186/s12865-026-00860-6","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-associated liver injury (SALI) is a risk factor for high mortality in patients with sepsis. However, the pathological mechanism and treatment strategies of SALI remain unclear. This study aims to explore the influence of lncRNA MIAT expression on SALI.</p><p><strong>Results: </strong>The MIAT and TXNIP levels in the serum of SALI patients, RAW264.7 stimulated by LPS, and AML-12 co-cultured with RAW264.7 were increased, while miR-942-3p expression was decreased. The secretion level of inflammatory factors, the ROS positive rate, and the MDA content were increased, while the GSH levels and SOD enzymatic activity were reduced in LPS-stimulated RAW264.7. The activity of AML-12 was decreased, and the LDH level was increased. When the MIAT was inhibited, the above results showed opposite trends. MIAT was a molecular sponge for miR-942-5p and represses its activity. After inhibiting miR-942-5p, the inflammatory response and the oxidative stress level were enhanced in LPS-stimulated RAW264.7 and the damage of AML-12 was worsened.</p><p><strong>Conclusions: </strong>The silence of MIAT alleviated the inflammatory response and oxidative stress in LPS-induced RAW264.7 and alleviated the damage of AML-12 cells by adsorbing miR-942-5p.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101012","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":"Correlation analysis of positive Alzheimer's disease plasma biological markers with plasma immune cell and clinical characteristics in mild cognitive impairment patients in China.","authors":"Lingling Wang, Penghui Zhang, Song Gao, Huiqin Liu, Xiaoting Qiu, Shuo Yang, Li Wei, Yanxia Li, Yijun Cai, Juan Yang","doi":"10.1186/s12865-026-00843-7","DOIUrl":"10.1186/s12865-026-00843-7","url":null,"abstract":"<p><strong>Objective: </strong>The aim of the present work was to investigate the correlation between positive Alzheimer's disease (AD) plasma biological markers and plasma immune cell content as well as clinical characteristics in mild cognitive impairment (MCI) patients.</p><p><strong>Methods: </strong>A total of 176 patients aged ≥ 65 years with MCI were followed up for two years. At baseline, AD plasma biomarkers (Aβ42, Aβ40, Aβ42/40, P-tau181 and PTau217) and immune cells (Treg cells, TH17 cells, lymphocytes) in MCI patients were detected, and their relevant clinical characteristics were recorded. Finally, the correlation between positive AD plasma biomarkers and immune cells, relevant clinical characteristics of MCI patients, and whether they would progress was analyzed.</p><p><strong>Results: </strong>Plasma Aβ42/40 levels are negatively correlated with age, a history of hypertension, constipation symptoms, and the TGF-β/Treg cell ratio. They are positively correlated with the TIM3+/Treg cell ratio, the number of CD19-positive cells, the CD4/CD8 ratio, and the number of CD8-positive cells. Plasma PTau217 levels are positively correlated with age, the proportion of B cells, and the proportion of NK cells, and negatively correlated with visual-spatial executive function and attention cognitive domain scores. Dual abnormalities of Aβ42/40 and PTau217 are positively correlated with age and the proportion of B cells, and negatively correlated with cognitive domain scores for executive ability, attention, and language ability.</p><p><strong>Conclusion: </strong>Abnormalities in AD plasma biomarkers are associated with immune activation (particularly B cells and NK cells), aging, cardiovascular and gastrointestinal risk factors, and cognitive decline. The concurrent abnormalities of multiple biomarkers may exacerbate these associations, although some immune regulatory pathways do not show significant effects.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13430910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052487","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":"MiR-100-5p is involved in severe pneumonia in children by targeting MTOR.","authors":"Lun Zhang, Qing Wang, Shoushan Mo","doi":"10.1186/s12865-026-00848-2","DOIUrl":"10.1186/s12865-026-00848-2","url":null,"abstract":"<p><strong>Background: </strong>Severe pneumonia in children is a life-threatening respiratory condition that can lead to severe complications and even mortality. We confirmed the possibility of miR-100-5p as a biomarker in severe pneumonia in children.</p><p><strong>Methods: </strong>A total of 200 children were included. The expression of miR-100-5p from serum was detected. WI-38 cells were treated with 10 µg/mL LPS for 24 h. miR-100-5p was overexpressed or inhibited by transfection. In addition, proliferation and inflammatory factors were measured. TargetScan was utilized to forecast the downstream of miR-100-5p. The targeting relationship between miR-100-5p and MTOR was confirmed by the dual-luciferase reporter system. miR-100-5p and MTOR were co-overexpressed to detect the function of both in severe pneumonia in children.</p><p><strong>Results: </strong>miR-100-5p expression was decreased and had a high diagnostic value in severe pneumonia in children. The miR-100-5p level was closely related to clinical indicators. In WI-38 cells treated with LPS, overexpression of miR-100-5p increased proliferation and reduced inflammatory factors, while inhibition of miR-100-5p reduced proliferation and increased inflammatory factors. MTOR expression was negatively associated with miR-100-5p expression in severe pneumonia in children.</p><p><strong>Conclusions: </strong>miR-100-5p may participate in severe pneumonia in children by negatively regulating MTOR, proving that it might be a biomarker of severe pneumonia in children.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13430885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052610","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":"Clinical role of miR-1271-5p in severe pediatric pneumonia and its prognostic value.","authors":"Junlin Chen, Li Wang","doi":"10.1186/s12865-026-00851-7","DOIUrl":"10.1186/s12865-026-00851-7","url":null,"abstract":"<p><strong>Background: </strong>As a predominant driver of pediatric mortality, severe pediatric pneumonia (SPP) is an important complication to be solved. The miR-1271-5p is universally engaged in pulmonary infection. This study focused on miR-1271-5p for the first time and aimed to reveal its role in SPP.</p><p><strong>Methods: </strong>The study enrolled 268 children aged 2-10 years, comprising 81 healthy individuals and 187 with pneumonia. The expression level of serum miR-1271-5p was assessed by qRT-PCR. The receiver characteristic (ROC) curve was employed to distinguish pneumonia children from healthy controls. Multivariate logistic regression analyzed factors associated with progression from mild-moderate pneumonia to SPP. Multivariate Cox regression assessed the association of miR-1271-5p expression with poor prognosis, and the Kaplan-Meier survival curve was subsequently generated based on miR-1271-5p levels.</p><p><strong>Results: </strong>Serum miR-1271-5p levels were remarkably elevated in children with pneumonia, especially SPP. Importantly, miR-1271-5p showed high diagnostic value of SPP, with the AUC of 0.877, the sensitivity of 74.9% and specificity of 87.8%. The results of multivariate logistic analysis demonstrated that miR-1271-5p was an independent risk factor for progression to SPP. Elevated serum miR-1271-5p levels were associated with poor prognosis in children with pneumonia and possessed predictive value for patients' adverse outcomes.</p><p><strong>Conclusion: </strong>Elevated serum miR-1271-5p was demonstrating superior diagnostic and prognostic specificity in severe pediatric pneumonia, providing a potential biomarker.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052456","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":"A conserved capsid-based multi-epitope vaccine targeting dengue virus serotypes (DENV1-4): an integrated computational and in vivo study.","authors":"Elham Mohammed Khatrawi, Syed Luqman Ali, Awais Ali, Syed Mudasser Ali, Hind Althagafi","doi":"10.1186/s12865-026-00857-1","DOIUrl":"10.1186/s12865-026-00857-1","url":null,"abstract":"<p><strong>Background: </strong>Dengue virus (DENV), comprising four antigenically distinct serotypes (DENV1-4), continues to pose a major global health burden. The lack of a universally protective vaccine capable of inducing balanced immunity against all serotypes remains a critical challenge, largely due to antigenic diversity and the risk of antibody-dependent enhancement (ADE). Conserved capsid proteins represent promising targets for epitope-based vaccine development because of their structural stability and immunogenic potential.</p><p><strong>Methods: </strong>An integrated reverse vaccinology and immunoinformatics strategy was employed to design a conserved capsid-based multi-epitope vaccine (MEV-DV) targeting DENV1-4. B-cell, cytotoxic T-lymphocyte (CTL), and helper T-lymphocyte (HTL) epitopes were screened for antigenicity, non-allergenicity, non-toxicity, and sequence conservancy. Selected epitopes were assembled using appropriate linkers with β-defensin as an adjuvant and a PADRE sequence. The construct was evaluated for physicochemical properties, 3D structure modeling and validation, solubility, disulfide engineering, molecular docking with TLR4 and TLR8, molecular dynamics simulation, and immune simulation. Experimental validation was performed in albino mice using an alum-adjuvanted formulation, and humoral responses were assessed by hemagglutination inhibition (HI) assay.</p><p><strong>Results: </strong>The finalized MEV-DV construct exhibited high antigenicity (0.8559), favorable physicochemical properties, and structural stability, with 97.6% of residues located in favored Ramachandran regions. Docking studies demonstrated strong binding affinity with TLR4 and TLR8, and molecular dynamics simulations confirmed stable receptor-vaccine interactions over 50 ns. Immune simulations predicted robust humoral and cellular immune responses with sustained memory formation. In vivo immunization induced detectable antibodies by day 7, with peak HI titers at day 21. Antibody levels were statistically comparable to those elicited by a commercial inactivated dengue vaccine (p > 0.05), and no adverse effects were observed.</p><p><strong>Conclusion: </strong>This study demonstrates that a conserved capsid-based multi-epitope vaccine designed through reverse vaccinology and immunoinformatics is structurally stable, immunogenic, and safe in a murine model. The combined computational and experimental findings support the potential of MEV-DV as a promising broadly protective dengue vaccine candidate and warrant further evaluation through neutralization assays and viral challenge studies.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027000","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":"Immunoinformatic design of a multi-epitope vaccine candidate targeting multidrug-resistant Pseudomonas aeruginosa.","authors":"Maryam Babaei, Behzad Shahbazi, Parisa Sarkoohi, Abolfazl Azadi, Kimia Jafari Ranjbar, Khadijeh Ahmadi","doi":"10.1186/s12865-026-00853-5","DOIUrl":"10.1186/s12865-026-00853-5","url":null,"abstract":"<p><strong>Background: </strong>Pseudomonas aeruginosa, a World Health Organization (WHO) priority pathogen, causes severe multidrug-resistant (MDR) infections in immunocompromised and hospitalized patients, highlighting the critical need for effective vaccines. To this end, we designed a novel multi-epitope vaccine by integrating immunodominant domains from three key virulence proteins (PcrV, OprE, and CupC2) with the cholera toxin B subunit (CTB) as a mucosal adjuvant.</p><p><strong>Methods: </strong>Immunoinformatics was used to predict epitopes and construct a vaccine with EAAAKEAAAK linkers. In silico assessments included antigenicity, allergenicity, solubility, molecular docking with TLR2/TLR4, 150 ns MD simulations, PDBsum interaction analysis, and C-ImmSim immune profiling.</p><p><strong>Results: </strong>Both the adjuvanted and non-adjuvanted candidates were predicted to be non-allergenic, with antigenicity scores of 0.6557 and 0.7338, respectively, indicating strong immunogenic potential. Both constructs were also predicted to exhibit high solubility, with scores exceeding the threshold (0.927 and 0.729). Each vaccine candidate showed robust interactions with TLR2 and TLR4; however, the adjuvanted construct demonstrated superior binding affinity to both receptors. Molecular docking of the adjuvanted vaccine candidate followed by 150 ns molecular dynamics (MD) simulations confirmed stable and strong interactions with TLR2 and TLR4, as evidenced by RMSD values of 0.64 nm and 0.73 nm, and binding energies of ΔG = - 15.9 kcal/mol and - 12.7 kcal/mol, respectively further supporting their high immunogenic potential. Moreover, in silico immune simulation data predicted rapid induction of protective antibodies and cytokines and revealed that adjuvant-enhanced responses substantially improved the stability of the TLR2 complex.</p><p><strong>Conclusion: </strong>These computational results suggest that our multi-antigen vaccine candidate may have potential against Pseudomonas aeruginosa infections. Further validation through gene synthesis, murine immunogenicity studies (e.g., BALB/c models), and challenge experiments is required.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013297","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":"Dynamic immune profiling enables early distinction between gastrointestinal GVHD and viral diarrhea after hematopoietic stem cell transplantation.","authors":"Man Chen, Xue-Qiao Wang, Jing Long, Min-Jing Fu, Hui Wang, Wei Zhao","doi":"10.1186/s12865-026-00850-8","DOIUrl":"10.1186/s12865-026-00850-8","url":null,"abstract":"<p><strong>Background: </strong>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is curative for hematologic malignancies, yet diarrhea after allo-HSCT-mainly due to gastrointestinal graft-versus-host disease (GI-GVHD) or viral infection-remains a major clinical challenge. Early etiological differentiation is essential for appropriate management.</p><p><strong>Aims: </strong>This study aimed to develop an immune-based predictive model by dynamically monitoring lymphocyte subsets and cytokines after allo-HSCT.</p><p><strong>Results: </strong>Among 232 patients who underwent allo-HSCT at Beijing Lu Daopei Hospital between 2021 and 2024, 58 developed biopsy-confirmed post-transplant (post-HSCT) diarrhea, comprising 34 cases of GI-GVHD and 24 cases of viral enteritis. Immune profiles were measured one week prior to diarrhea onset, as well as at weeks 4 and 5 post-HSCT. Predictive features were selected using LASSO and logistic regression to construct single- and multi-time-point models, which were validated using nomogram, calibration, and decision curve analyses. At the pre-diarrhea point, patients with aGVHD had higher Reg3α, CD3⁺T%, CD8⁺T%, naive CD4⁺/CD4⁺T%, and Th2/CD4⁺T%, but lower NK count and NK% (all P < 0.05). The single-time-point model achieved good discrimination (AUC = 0.799), while the multi-time-point model integrating nine dynamic parameters showed superior accuracy (AUC = 0.908).</p><p><strong>Conclusions: </strong>Dynamic immune profiling may aid in the early distinction between GI-GVHD and viral enteritis, highlighting its potential as a tool for immunological surveillance to guide intervention after allo-HSCT.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013375","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":"Deficient TRPM3-linked mitochondrial Ca²⁺ influx in natural killer cells associated with myalgic encephalomyelitis/chronic fatigue syndrome.","authors":"Chandi Tabeth Magawa, Natalie Eaton-Fitch, Katsuhiko Muraki, Sonya Marshall-Gradisnik","doi":"10.1186/s12865-026-00849-1","DOIUrl":"10.1186/s12865-026-00849-1","url":null,"abstract":"<p><strong>Introduction: </strong>Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystemic illness, commonly associated with dysregulation of the immune system including reduced cytotoxicity of natural killer (NK) cells and post-exertional neuroimmune exhaustion. Previously, transient receptor potential melastatin 3 (TRPM3) ion channel impairment associated with reduced Ca²⁺ mobilisation in NK cells from ME/CFS patients was reported. To further explore the pathomechanisms involved in ME/CFS, we investigated the downstream impact of TRPM3 ion channel dysfunction on mitochondrial Ca²⁺ mobilisation in NK cells.</p><p><strong>Method: </strong>Fluorescence live-cell imaging was used to investigate Ca²⁺ mobilisation in NK cells of (N = 10) ME/CFS, classified using Canadian Consensus Criteria, and (N = 10) healthy control (HC) participants. Cytoplasmic and mitochondrial Ca²⁺ entry was determined using Fluo-8 AM and Rhod-2 AM Ca²⁺ indicators, respectively. The effect of TRPM3 modulation on Ca²⁺ mobilisation ex vivo, was examined using pregnenolone sulfate and ononetin to activate and inhibit the channel, respectively.</p><p><strong>Results: </strong>Cytosolic Ca²⁺ influx amplitude and slope were significantly reduced (p < 0.001), with a significantly shorter T_1/2 response (p = 0.001) in ME/CFS compared to HC. Ca²⁺ influx amplitude (p < 0.001) and slope (p < 0.041) into the mitochondria were significantly higher in ME/CFS compared to HC. TRPM3 activation triggered pronounced cytosolic response (P < 0.001) accompanied by mitochondrial Ca²⁺ increase in HC. TRPM3-dependent cytosolic and mitochondrial Ca²⁺ mobilisation (P < 0.015) were significantly reduced with a shorter T_1/2 response (p < 0.02) in ME/CFS compared to HC.</p><p><strong>Conclusion: </strong>The results demonstrate that altered TRPM3-mediated cytosolic Ca²⁺ influx may significantly impact Ca²⁺ mobilisation into the mitochondria of people with ME/CFS. Alterations that interfere with the optimal function of Ca²⁺ permeable channels may cumulatively impact downstream signalling, leading to detrimental cellular consequences. Collectively these findings provide an avenue for further studies on the physiological functions of TRPM3 ion channel and its role in ME/CFS.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004590","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}