Search Results (987)

Environmental, genetic, immunological and metabolic factors are involved in renal cell carcinoma development. Clear cell renal carcinoma (ccRCC) is the most frequent renal cancer, with a complex metabolic physiopathology. The present study focuses on the characterization of chemical changes in glutathione redox homeostasis induced by oxidative damage and their relevance to ccRCC. We developed a prospective, case–control study that included 92 subjects diagnosed with ccRCC by histopathological exam and 40 healthy subjects. In each subject, we evaluated the chemical changes in glutathione redox homeostasis, antioxidative capacity, nitrosative stress, carbonyl stress, inflammation (IL-12 family members, albumin), angiogenesis factors and apoptosis. Compared to the control, in ccRCC subjects, we detected high levels of oxidative/electrophile stress, of hypoxia, and of inflammatory- and angiogenesis-related factors and low levels of anti-inflammatory-, anti-oxidative- and apoptosis-related factors. In ccRCC, positive correlations between glutathione redox homeostasis members expression and electrophile metabolites levels, respectively, angiogenesis markers and inflammatory parameters detected. Negative relations with anti-inflammatory and antioxidant markers were assessed. Glutathione redox homeostasis was altered in ccRCC, functioning as an active redox mechanism, with an essential role in the development and progression of ccRCC. Full article

Endovascular therapies have transformed cardiovascular medicine, yet restenosis, thrombosis, and device failure remain common and poorly predictable complications. Increasing evidence suggests that immunothrombotic processes critically shape vascular recovery after device implantation. This includes neutrophil extracellular trap (NET) formation, innate immune polarization, and endothelial damage responses. Concurrently, advances in artificial intelligence (AI) are increasingly enabling continuous multimodal monitoring and adaptive clinical decision-making throughout the medical device life cycle. Here, we propose the concept of immunologically adaptive endovascular devices: a closed-loop paradigm in which patient immune status informs device selection, device–tissue interactions are interpreted via mechanistic biomarkers, and real-world monitoring dynamically updates risk and management. The study introduces (i) an immune–device interaction phenotype taxonomy linking device design features to measurable thrombo-inflammatory trajectories, (ii) a mechanistic framework defining interface signaling processes that enhance or resolve NET-driven responses, (iii) a minimum evidence model encompassing preclinical testing, clinical validation, and post-market surveillance, and (iv) a reference AI architecture for risk prediction, drift detection, and safety monitoring. This study also outlined testable predictions and a translational roadmap toward precision endovascular intervention and next-generation adaptive cardiovascular devices. Full article

RCC remains a therapeutically challenging malignancy, particularly in its metastatic stage, in which treatment resistance and limited response durability persist despite recent advances in immunotherapy and targeted therapies. Although immune checkpoint inhibitors (ICIs) have significantly improved outcomes for a subset of patients, reliable prognostic and predictive biomarkers to guide therapy selection are still lacking. Current clinical models, such as the International Metastatic RCC Database Consortium (IMDC) risk score, offer only limited insight into the molecular and immunologic complexity of RCC. Emerging molecular biomarkers implicated in resistance mechanisms reflect the underlying heterogeneity of RCC and may inform future therapeutic strategies. Kidney Injury Molecule-1 (KIM-1), a transmembrane protein that is up-regulated in RCC and detectable in circulation, has demonstrated potential as a non-invasive biomarker for diagnosis, prognosis, and treatment monitoring. Liquid-biopsy approaches, including the analysis of circulating tumour DNA (ctDNA), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs), are also gaining traction due to their minimally invasive nature and potential for real-time disease monitoring. This review aims to provide a structured overview of emerging biomarkers in metastatic RCC, critically evaluate their current clinical applicability, and propose a biologically informed framework for their integration into clinical decision-making. In addition, we propose a conceptual IMDC-Plus framework that integrates clinical, biological, and early dynamic markers to improve risk stratification in the era of immunotherapy (IO). Full article

Currently, the B-cell response patterns induced by viral antigens in avian disease models and their detailed immunological characteristics still require comprehensive elucidation at the single-cell level. In this study, we employed single-cell sequencing (scRNA-seq) and B cell library technology to conduct an in-depth analysis of B cells in the spleens of mice with inactivated duck hepatitis A virus type 1 (DHAV-1) as model antigen. This study aimed to investigate the immunological characteristics of the virus antigen in the mouse model and characteristics of B-Cell Receptors. The results showed that the DHAV-1 group had distinct changes in splenic B cell subset counts, proportions, and intercellular communication. Additionally, an increased trend in communication strength between Gm26917+B and Gm11837+B cells was observed, with enriched expression of C-X-C motif chemokine ligand (CXCL) and lymphotoxin (LT) detected in the DHAV-1 group. Furthermore, the DHAV-1 group exhibited a prominent combination of the IGHV1 family and IGHV3-1/IGHJ3 in the heavy (H) chain variable region. Compared with the CK group (negative control group), the amino acid sequence length and diversity of the CDR3 region in the DHAV-1 group exhibited a decreasing trend. In summary, our findings characterize the immunological features of splenic B cells in mice after immunization with inactivated DHAV-1, and provide a preliminary characterization of DHAV-1-induced B cell transcriptional states and BCR repertoire features, generating testable hypotheses for subsequent mechanistic investigations of B cell-mediated immune responses to viral antigens. Full article

Background: Renal allograft rejection remains a major challenge in transplantation. Current diagnostic approaches, including biopsies, are invasive and may fail to detect subclinical immune activation, potentially contributing to progressive graft dysfunction. Reliable, non-invasive biomarkers capable of monitoring immune activation and distinguishing rejection phenotypes are therefore needed. Methods: In this retrospective study, we evaluated serum neopterin as a biomarker of immune activation and graft status over 12 months following transplantation. Associations between neopterin levels and immune parameters, including natural killer (NK)-to-CD3⁺CD16/CD56⁺ T cell ratios, cytokines (IFN-γ and IL-10), and CD4⁺CD25⁺FoxP3⁺ T cell frequencies, were assessed. A total of 211 first renal allograft recipients were followed longitudinally, including patients with acute rejection (AR) and matched stable graft (SG) recipients. Serum neopterin was quantified by enzyme immunoassay, and immunophenotyping, mRNA expression, and cytokine profiling were performed on peripheral blood samples. Results: Serum neopterin levels were significantly elevated in AR compared to SG recipients, with a threshold of 57 nmol/L distinguishing AR with 81% sensitivity and 80% specificity. While IFN-γ demonstrated higher diagnostic performance in cross-sectional analysis, neopterin showed a more sustained elevation over time, remaining increased in AR recipients even at later post-transplant time points. Neopterin correlated positively with IFN-γ, but not IL-10, and inversely with CD4⁺CD25⁺FoxP3⁺ T cell frequency. NK cells were enriched during rejection, whereas CD3⁺CD16/CD56⁺ T cells were more prominent in graft stability. The NK-to-CD3⁺CD16/CD56⁺ T cell ratio was highest during acute cellular rejection. Conclusions: Neopterin reflects Th1-associated immune activation in renal allograft recipients and provides a temporally stable, non-invasive marker of immune status. Although it does not outperform IFN-γ levels at the time of rejection, its stability and sustained elevation suggest a complementary role in longitudinal monitoring. Integration of neopterin with immune parameters, including cytokine profiles and cellular subsets, may enhance the assessment of graft immunological status and support clinical decision-making. Full article

Kidney transplant recipients (KTRs) remain vulnerable to infectious complications and malignancies due to chronic immunosuppression, both of which may contribute to allograft dysfunction and adverse clinical outcomes. This study aimed to evaluate the prevalence of viral infections and post-transplant malignancies among hospitalized KTRs and to identify factors associated with acute kidney injury (AKI) and chronic graft dysfunction. We conducted a prospective observational study including 215 adult KTRs admitted to a tertiary transplant center over a one-year period. Clinical data, malignancy history, and viral detection for BK polyomavirus (BKV), cytomegalovirus (CMV), Epstein–Barr virus (EBV), and parvovirus B19 were analyzed. AKI occurred in 65.6% of patients, while chronic graft dysfunction was present in 21.4%. Viral positivity was detected in 16.7% of the cohort, most frequently BKV and CMV. Infectious etiologies represented the most common cause of AKI. Viral positivity was significantly associated with infectious mechanisms of AKI and was independently associated with AKI in multivariable analysis (adjusted OR 3.01, p = 0.02). In a separate multivariable model, malignancy history (aOR 9.30), viral positivity (aOR 3.33), and concurrent AKI (aOR 3.42) were independently associated with chronic graft dysfunction. These findings suggest that viral reactivation and malignancy history cluster with clinical states of increased graft vulnerability in hospitalized KTRs. Integrated evaluation of infectious, immunologic, and clinical factors may improve risk stratification and management of transplant recipients presenting with acute illness. Full article

Peritoneal dialysis (PD)-associated peritonitis in children represents a complex interplay between microbial virulence, host immune activation and progressive peritoneal membrane remodeling. It should not be viewed solely as an acute infectious episode, but as a process unfolding within a chronically conditioned immune environment shaped by prolonged exposure to glucose-based dialysis solutions, oxidative stress and persistent biofilm formation on the Tenckhoff catheter. Mesothelial cells act as immunologically active sentinel cells, recognizing pathogen-associated molecular patterns through Toll-like receptors and related innate pathways. Subsequent activation of nuclear factor kappa B, inflammasome signaling and neutrophil extracellular trap formation further amplifies local inflammatory responses. Repeated inflammatory stimulation promotes mesothelial–mesenchymal transition, angiogenesis and extracellular matrix deposition driven by transforming growth factor beta 1 and interconnected profibrotic networks. In pediatric patients, prolonged PD vintage during critical stages of growth may intensify cumulative structural injury and increase the risk of ultrafiltration failure or encapsulating peritoneal sclerosis. Emerging strategies targeting inflammation, fibrosis and biofilm persistence, together with earlier molecular risk detection, may support preservation of the peritoneal membrane. A unified host–pathogen framework may therefore deepen pathophysiological insight and facilitate more individualized therapeutic strategies in pediatric PD. Full article

Bronchoscopic cryotherapy is routinely used for endobronchial tumor debulking, but may also exert systemic immunologic effects that could interact with immune checkpoint blockade. We investigated peripheral blood T-cell dynamics following bronchoscopic cryotherapy and subsequent pembrolizumab-based first-line therapy in metastatic non-small-cell lung cancer (NSCLC). In this prospective, randomized, controlled single-center study, patients with metastatic NSCLC were randomized into treatment groups of bronchoscopic cryotherapy performed 7 (±1) days before standard-of-care pembrolizumab (with or without platinum-based chemotherapy) or to standard-of-care therapy alone. Peripheral blood mononuclear cells were analyzed by flow cytometry at baseline, week 3, and week 6. Radiologic response was assessed using RECIST 1.1. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan–Meier test and Cox regression. Flow cytometry was performed on 34 cryotherapy and 42 control patients. The cryotherapy group demonstrated a decrease in circulating CD4+ T cells (p = 0.002) and an increase in circulating CD8+ T cells (p = 0.013) by week 6. CD25+FOXP3+CD4+ Tregs decreased from baseline to week 3 (p = 0.024) and remained reduced through week 6. Overall response rate was higher in the cryotherapy group (41.2% vs. 16.7%; p = 0.022), while PFS and OS were numerically longer, although not statistically different (median PFS 9.5 vs. 5.3 months; median OS 17.6 vs. 14.8 months). The decrease in Tregs at week 3 was observed to predict better PFS. In patients with metastatic NSCLC receiving first-line pembrolizumab with or without chemotherapy, the addition of bronchoscopic cryotherapy was associated with a detectable peripheral immune remodeling and a higher objective response rate, whereas PFS and OS were numerically longer but not statistically different. Full article

Cell-based immuno-biosensors are novel platforms for studying immune responses of biological cells, with real-time insights more similar to physiological and pathological conditions. These systems utilize living immune cells as their main components, enabling them to detect disease-related biomarkers and cellular traits in a way that is often highly sensitive and label-free. Integration with microfluidics and organ-on-chip technologies has facilitated precise manipulational control over the cellular microenvironment. Not only has this resulted in high-throughput screening, but it also enabled smaller, more portable systems which can be used at the point of care. In this work, we review the recent advance in microfluidic cell-based immuno-biosensing associated with immune cells such as neutrophils, macrophages, T cell and dendrite cells. Some of the exciting developments include fusion with methods such as advanced imaging, electrical impedance sensing and application of machine learning to phenotyping. We will also elaborate on the issues related to the standardization of these systems, cell heterogeneity, and the challenges for translating these technologies for clinical application. Taken together, such integrated platforms have potential to fill the gap left in-between cellular immunology with biosensor engineering. Full article

Myasthenia gravis (MG) is a prevalent autoimmune disorder affecting neuromuscular junctions, typically characterized by muscle weakness due to autoantibodies targeting acetylcholine receptors (AChR) or muscle-specific kinase (MuSK). Generalized MG is a more severe form of the condition than ocular MG. Although MG can strike at any age, young adult women are typically affected, especially in their reproductive years. MG is rare during pregnancy, with the first trimester and the postpartum period being the most common times for exacerbations. The influence of MG on pregnancy outcomes remains ambiguous, with some studies finding larger prevalence of issues such as preterm birth and small-for-gestational-age babies, while others indicate results similar to the general population. Management of MG during pregnancy necessitates careful monitoring and drug adjustments. Teratogenic concerns make several immunosuppressive drugs, such mycophenolate mofetil and methotrexate, contraindicated. In contrast, medications like prednisolone and pyridostigmine are generally recognized as safe. Women with MG may have flare-ups after giving birth, and infants may have transient neonatal myasthenia gravis. Comprehensive prenatal treatment and multidisciplinary assistance are crucial for promoting maternal and fetal health during pregnancy in women with MG. This paper examines the relevance of immunological biomarkers, RNAs, and other novel biomarkers in myasthenia gravis (MG). It emphasizes the need for more investigation to determine their role in the pathogenesis of MG, evaluate biomarker profiles across subgroups, and look at changes after treatment. The study also underlines the significance of high-throughput investigations to detect new biomarkers and reveal genetic variables impacting MG pathogenesis. Full article

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease in which renal involvement is a major determinant of prognosis and is classically dominated by amyloid A (AA) amyloidosis. Non-amyloid renal manifestations are uncommon and poorly characterized. We report a case of clinically overt FMF associated with anti-phospholipase A2 receptor (PLA2R) antibody-positive membranous nephropathy (MN). A 46-year-old man with recurrent febrile episodes fulfilling Tel Hashomer criteria for FMF developed progressive proteinuria with detectable anti-PLA2R antibodies. Genetic testing identified a heterozygous missense MEFV variant in exon 10 (p.Lys695Arg), a mutation with variable penetrance and conflicting pathogenic classification. Kidney biopsy demonstrated PLA2R-positive MN, excluding amyloidosis. After initial conservative management, the patient progressed to nephrotic syndrome complicated by renal vein thrombosis, requiring immunosuppressive therapy according to the Ponticelli regimen in addition to colchicine and anticoagulation, resulting in clinical and immunological remission. In parallel, we performed a systematic review of the literature, identifying only isolated reports of biopsy-proven MN in FMF patients. This case highlights the diagnostic importance of kidney biopsy in FMF patients with proteinuria and illustrates that immune-mediated glomerular disease may occur even in association with non-founder or variably penetrant MEFV mutations, requiring disease-specific management beyond standard autoinflammatory control. Full article

Escherichia coli O157:H7 (E. coli O157:H7) is a highly virulent foodborne pathogen with an extremely low infectious dose, making its rapid and accurate detection in food and environmental samples critically important. In recent years, significant progress has been made in immunological techniques for the rapid identification of E. coli O157:H7. This review systematically summarizes advances in immunological methods for the detection of E. coli O157:H7 over the past decade, focusing on lateral flow immunoassays (LFIA), enzyme-linked immunosorbent assays (ELISA), immunosensors (optical and electrochemical), and nanobody-based technologies. Key aspects such as detection principles, specificity, antibody types (monoclonal, polyclonal, nanobodies), signal readout mechanisms, and applicability to different sample matrices are compared. Performance parameters, including limit of detection (LOD), specificity, detection time, and matrix compatibility, are summarized to evaluate the advantages and limitations of each method. Furthermore, international food safety standards and regulations (ISO 16654, FDA BAM, USDA) are reviewed to highlight the practical and regulatory requirements of these techniques. On this basis, the role of immunological detection technologies in on-site rapid testing is discussed, with a focus on improvements in sensitivity, specificity, and practicality. Finally, future directions are outlined, including multiplexed assays, integration with molecular biology techniques, and engineering applications of nanobody and recombinant technology. Full article

Oropouche virus (OROV) is an emerging arthropod-borne virus in the Americas that has evolved from a pathogen historically restricted to forest environments into an increasingly important regional and international public health concern. Despite decades of documented circulation, the true burden of OROV infection remains substantially underestimated, largely because of frequent misdiagnosis and the high proportion of asymptomatic or subclinical infections. This review synthesizes current evidence on the historical emergence, epidemiology, transmission dynamics, and clinical features of OROV, with a particular focus on populations at increased risk due to biological susceptibility, environmental exposure, and limited access to healthcare. Drawing on seroepidemiological data, we demonstrate that OROV transmission is far more widespread than routine surveillance suggests and examine how factors such as age, pregnancy, immune status, underlying health conditions, occupational exposure, and healthcare accessibility interact to influence disease risk and detection. Although multiple vaccine platforms have shown promise in preclinical studies, progress toward clinical development remains constrained by limited immunological evidence, shortcomings of available animal models, diagnostic uncertainty, and structural barriers in endemic regions. We propose that future OROV vaccine development prioritize population-specific needs rather than focusing solely on technological platforms, and that effective prevention will require integrating vaccination with strengthened surveillance, improved diagnostics, and equitable delivery systems. Full article

Clinical, experimental, and computational evidence of COVID-19 virulence and infectivity has been linked to SARS-CoV-2 shell disorder. A strong link was first discovered using an AI disorder-predicting tool, which detected an unusually hard (low disorder) outer shell among all SARS-CoV-2-related viruses but not in the 2003 SARS-CoV-1. This could account for the high infectivity found in SARS-CoV-2—but not in SARS-CoV-1—as it is believed that hard shells protect viral particles from the onslaught of the antimicrobial enzymes present in the respiratory system and saliva. As a result, much larger quantities of particles are shed by COVID-19 patients. Abnormally hard outer shells (M) are associated with burrowing animals, e.g., pangolins, and SARS-CoV-2 likely acquired these shells due to its long-term evolutionary interactions with pangolins. As for virulence, the inner shell of SARS-CoV-2 (N) has been found to exhibit lower disorder than that of SARS-CoV-1. This lower disorder is consistent with the fact that SARS-CoV-2 is less virulent than SARS-CoV-1, as higher disorder in the inner shell is associated with more efficient protein–protein binding during replication. The link between N/M disorder and virulence or infectivity falls under the umbrella of shell disorder models (SDMs), which can connect virulence, infectivity, and long COVID under one coherent concept. Evidence of the reliability and reproducibility of SDMs as applied to COVID-19 is examined. The hard M that is resisting the antimicrobial enzymes in the respiratory system can be extended to immunological enzymes, especially those found in phagocytes such as macrophages, which can therefore become a reservoir for the virus. Full article

Viral and bacterial pathogen pathogens cause disease outbreaks that challenge the pearl gentian grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂) industry’s sustainable development. The lack of monoclonal antibodies (mAbs) targeting serum immunoglobulin M (IgM) in this hybrid grouper impedes the development of non-lethal immunoassays for detecting pathogen infections, as well as research on immune responses following vaccination. We purified serum IgM from hybrid pearl gentian grouper and generated two mAbs—designated 41-H2-E1 and 62-E8-G9—against the purified IgM, finding that mAb 62-E8-G9 specifically recognized the IgM heavy chain, whereas mAb 41-H2-E1 specifically recognized the light chain. In indirect immunofluorescence assays, both mAbs reacted with surface Ig-positive (sIg⁺) lymphocytes. A double-antibody sandwich ELISA was subsequently established using mAb 62-E8-G9 as the capture antibody and HRP-conjugated mAb 41-H2-E1 as the detection antibody, enabling accurate quantification of serum IgM levels. Significant differences in IgM concentrations were observed between larger and smaller individuals (9.11 μg/mL vs. 3.84 μg/mL, p < 0.05). In immunostimulant administration experiments, both low-and high-dose groups exhibited approximately 2.0-fold higher IgM levels than the control group (p < 0.05). In contrast, vaccination with inactivated vaccines did not result in statistically significant differences in total IgM levels. mAb 41-H2-E1 was further applied to detect Vibrio parahaemolyticus- and Vibrio harveyi-specific immunoglobulins in serum under different vaccination regimens. Collectively, these findings demonstrated that the mAbs developed in this study served as reliable immunological tools for investigating immune function in hybrid pearl gentian grouper. Full article