Neutrophils contribute to systemic lupus erythematosus (SLE) pathogenesis through ROS and NET production, and increased apoptotic debris which causes autoantibody production and immune complex formation. These processes drive inflammation and tissue damage. The aim of this study was to perform integrated transcriptomic and metabolomic analyses comparing paediatric and adult SLE neutrophils. Adult (aSLE) and pediatric (jSLE) patient and healthy adult (HA) and juvenile (HJ) control neutrophils were subjected to RNAseq and 1H-NMR metabolomics. Univariate, multivariate and multiomics enrichment analyses were conducted in R and with Ingenuity Pathway Analysis (IPA). Transcriptomic analysis revealed distinct gene expression profiles. Adult and juvenile SLE neutrophils were enriched for genes regulating IFN-α/β signalling, neutrophil degranulation and NET signalling pathways (IPA, adj.p-value<0.01). Gene Ontology analysis revealed enrichment in cell cycle and interferon signalling in aSLE, and angiogenesis and tissue-specific development in jSLE. Metabolomic profiling identified distinct metabolic alterations in aSLE, with a greater complexity of metabolic changes in jSLE. Multivariate PLS-DA demonstrated group discrimination, particularly in aSLE (balanced accuracy 80%, sensitivity 80%). VIP>1 metabolites were enriched in taurine/hypotaurine and amino acid metabolism in aSLE. Integrating transcriptomic and metabolomic data strengthened IFN-α/β signalling, neutrophil degranulation and NET signalling (adj. p <0.001). Additional metabolic pathways uniquely down-regulated in aSLE included glutamate and glutamine metabolism, nucleotide biosynthesis and tryptophan catabolism (adj.p<0.01). In summary, neutrophils from SLE patients, especially in jSLE, displayed complex transcriptomic and metabolic profiles, with aberrant IFN responses and neutrophil activation.

Neutralizing autoantibodies against type I interferons are a risk factor for multiple severe viral diseases. The timely detection of these autoantibodies remains an unmet need.

To evaluate cluster of differentiation (CD)38 expression in peripheral blood lymphocyte subsets in patients with primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) and explore its association with glaucoma onset and severity.

Dysfunction of the blood-brain barrier (BBB) plays a pivotal role in the pathogenesis of neuromyelitis optica spectrum disorders (NMOSD). AIMP1 as a novel proinflammatory factor with anti-angiogenic properties is closely related to the destruction of the BBB. However, its role in the pathogenesis of NMOSD remains unclear.

The programmed cell death protein 1 (PD-1), expressed mainly by T lymphocytes, is an important checkpoint of the immune response and may contribute to tumorigenesis when associated with its ligands, PD-L1 or PD-L2, expressed by tumor cells. In this context, this study aimed to analyze the allelic variants rs11568821 G>A and rs41386349 C>T of the PDCD1 gene in breast cancer patients and cancer-free women and correlate them with clinical-pathological parameters.

Cytokine storm can result from uncontrolled pro-inflammatory cytokines released in SARS-CoV-2 infection that cause damage to several organs. Il-6 is one of the major mediators of cytokine storm. IFN-α2 has been reported to have anti-viral potential and the pre-infection levels of pro-inflammatory cytokines have been suggested to drive the fate of the disease. There is a paucity of information on how anti-viral cytokines at the onset of infection affect the disease progression. This study aims to profile IL-2, IL-6, IL-10, and IFN-α2 expression levels for 44 days post-diagnosis and their effects on recovery. Peripheral venous blood was collected from 38 SARS-CoV-2 infected participants who came for diagnosis at the Centre for Research on Emerging and Re-emerging Diseases. IL-2, IL-6, IL-10, and IFN-α2 levels were measured using a Luminex panel. Males had higher SARS-CoV-2 viral load than females, although the difference was not statistically significant (P = 0.08). Age-related variation was also observed, with individuals aged 40-60 showing significantly higher viral load than those over 60 (P = 0.045). Cytokines analysis revealed that males had significantly higher levels of IFNα-2, IL-2, and IL-6 (P = 0.0031, P = 0.009, and P = 0.022 respectively) than females upon diagnosis, with cytokines levels decreasing over time in males but increasing in females. Cytokine levels trended higher in symptomatic individuals, although differences were not significant. These findings highlight the influence of sex, clinical status, and viral load on cytokine dynamics in COVID-19, with potential implications for understanding disease severity and immune response.

B-cell maturation antigen (BCMA) is a B cell surface receptor that regulates B cell activation, proliferation and survival. BCMA can be cleaved from the cell surface, producing soluble BCMA (sBCMA), which has been studied as a disease biomarker in systemic lupus erythematosus, multiple sclerosis and multiple myeloma. Reduced sBCMA concentrations have been associated with the severity of different primary antibody deficiencies. We explored the relationship between sBCMA concentrations, humoral immune responses to SARS-CoV-2 vaccination and disease complications in 107 individuals with primary (PAD) and secondary antibody deficiency (SAD) enrolled in the COVID-19 in Antibody Deficiency (COV-AD) study. Serum sBCMA concentrations were significantly reduced in PAD compared to healthy controls and asymptomatic selective IgA deficiency. Individuals with X- linked agammaglobulinemia and common variable immunodeficiency (CVID) demonstrated the lowest serum concentrations of sBCMA. sBCMA concentrations in SAD were highly variable. Amongst individuals with CVID, peripheral blood CD19 count, but not sBCMA concentrations discriminated SARS-CoV-2 vaccine responders. sBCMA was significantly lower in individuals with CVID and bronchiectasis and outperformed serum IgA and IgM concentrations in discriminating this subgroup. sBCMA was not associated with any other complication of CVID. Our data highlights the potential of sBCMA as biomarker to support the assessment of antibody deficiency. In PAD, sBCMA may contribute to the risk stratification of disease severity and identify those at risk of bronchiectasis. In SAD, it may identify subgroups that would benefit from intensive monitoring and therapy.

Children with recurrent infections present a diagnostic challenge due to the wide overlap between normal childhood infections and primary immunodeficiency diseases. Predominantly antibody deficiencies are the most common category of primary immunodeficiency disease in this population. While many predominantly antibody deficiency cases are identified through markedly low immunoglobulins levels or reduced B cell counts, some demonstrate subtler forms such as IgG subclass deficiency or specific antibody deficiency, which may present similar clinical symptoms but normal standard laboratory parameters. Diagnosing these conditions in children is particularly challenging due to the overlap with physiological immune immaturity and the high incidence of infections in early childhood. Clinicians must carefully distinguish between benign infection patterns and true immunodeficiencies to avoid missed diagnoses and unnecessary investigations. This review summarizes key findings on IgG subclass deficiency and specific antibody deficiency, highlights their clinical relevance in paediatric practice, and evaluates current challenges in diagnosis and classification. We also discuss the overlap between these conditions and propose a structured approach to improve diagnostic consistency. Addressing these knowledge gaps is essential to optimize care for children with recurrent infections and suspected antibody deficiencies.

Using flow cytometry, we assessed circulating T4sen and T8sen proportions at baseline and 3 months after initiating anti-TNF treatment in RA and SpA patients using flow cytometry. Circulating levels of cytokines were measured at baseline. These parameters were associated with demographic variables and disease activity. T4sen and T8sen were compared between RA, SpA, SjD, healthy donors, and cancer patients. T8sen, but not T4sen, accumulated more in patients with IMIDs than in patients with lung cancer and healthy donors. CMV-seropositivity was associated with the accumulation of T8sen. T8sen were associated with high IL-6 in SpA patients and high IP-10 in SjD patients. Anti-TNF did not impact the T8sen proportion of RA and SpA patients. There was a trend toward an increase in T8sen in anti-TNF nonresponders after 3 months of treatment. Senescent CD8 T cells are enriched in IMID patients, suggesting that immune aging is a shared feature of chronic inflammatory diseases. The association between T8sen and distinct inflammatory cytokines underscores the potential role of senescence in shaping immune responses in IMIDs.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disorder of the sinonasal mucosa, predominantly characterized by epithelial dysfunction and chronic heterogeneous mucosal inflammation. CRSwNP and asthma are common comorbidities with overlapping pathophysiology, epithelial impairment, and activation of downstream type 2 inflammation. Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine that sits at the top of the immunological cascade and initiates and amplifies type 2-dependent and -independent inflammatory responses. Although the role of TSLP in asthma has been well described, the role of TSLP in CRSwNP has yet to be comprehensively outlined. This review examines the evidence for TSLP as a key factor in CRSwNP pathogenesis. We explore what is known about TSLP expression patterns within the sinonasal mucosa, finding that TSLP expression is increased in patients with CRSwNP compared with healthy patients, and in eosinophilic- versus non-eosinophilic CRSwNP. We discuss the impact of environmental triggers and genetic factors on TSLP expression and activity, as well as other upstream regulators of TSLP signaling. We then consider the known mechanisms and effects of TSLP signaling on the recruitment and activation of various immune and structural cell types in CRSwNP. Finally, we consider the available evidence on the therapeutic potential of targeting TSLP signaling for the treatment of CRSwNP and discuss ongoing trials of promising therapeutic candidates.

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus with well-established oncogenic potential, contributing to various malignancies and immune-mediated diseases. Its capacity to infect and immortalize B-cells forms the basis for the generation of lymphoblastoid cell lines (LCLs), which serve as vital models in immunology, virology, and translational research. While conventional LCLs are produced by exogenous EBV infection of peripheral blood mononuclear cells, spontaneous lymphoblastoid cell lines (S-LCLs) can emerge without deliberate viral inoculation, particularly in EBV-seropositive individuals. This review highlights multiple methodologies used to establish S-LCLs, including the use of cyclosporin A, CpG DNA, checkpoint kinase inhibitors, and cytokine modulation, and presents findings from diverse clinical contexts such as autoimmune diseases, post-transplant lymphoproliferative disorders, and cancer. We discuss the biological mechanisms underpinning EBV latency and reactivation, emphasizing the viral transcriptional programmes that drive B-cell transformation and persistence. Additionally, we explore how cytokines, particularly IL-10, support S-LCL survival, and how sodium butyrate and antiviral agents like acyclovir can influence EBV reactivation and replication. The review also considers the diagnostic and therapeutic relevance of LCLs, including their potential as antigen-presenting cells, vaccine platforms, and models for cellular immunotherapies such as CAR T-cells and virus-specific cytotoxic T lymphocytes. By evaluating the generation, molecular features, and immunological significance of S-LCLs, this review underscores their value in modelling EBV-driven disease and advancing novel therapeutic strategies.

Oral keratinocytes are pivotal to the structural and immunological integrity of the oral mucosa, orchestrating mucosal defense through multifaceted immune functions. This narrative review synthesizes mechanistic insights from primary keratinocyte cultures, in vitro infection models, transcriptomic and proteomic profiling, and immunohistochemical analyses to elucidate their roles in pathogen sensing via pattern recognition receptors, antimicrobial peptide production, cytokine secretion, antigen presentation, immune modulation, and tolerance induction. The review highlights their contributions to innate and adaptive immunity, including the secretion of antimicrobial peptides such as β-defensins and the regulation of T-cell responses through major histocompatibility complex molecules. It also examines their dysregulation in chronic inflammatory conditions, such as oral lichen planus, recurrent aphthous stomatitis, and periodontitis, where altered pattern recognition receptors signaling and barrier dysfunction drive disease progression. These insights underscore the therapeutic potential of targeting keratinocyte-mediated immunity to restore mucosal homeostasis.

Although celiac disease (CD) current and only treatment is a life-long strict gluten-free diet (GFD), some patients suffer from persistent duodenal lesions despite years into the diet. Hence, we aimed to study the effect that the GFD elicits on the mucosal immune infiltrate from these patients.

Dysregulation of interleukin (IL) 16 has been implicated in SLE, yet its cellular source and role in disease pathogenesis remain unclear. We analysed circulating IL16+ immune cells from 40 SLE patients, including 32 with active disease (SLEDAI-2K ≥ 4) using spectral flow cytometry. Plasma (pIL16) and urine IL16 (uIL16) levels were measured, and correlations with clinical variables were assessed. IL16 effects on T cell migration were studied in vitro. Active SLE patients showed broadly reduced proportions of cells expressing IL16, including CD4+T, CD8+T, B, and NK cells. This reduction was prominent in several cell subsets including Th1-like cells and plasmablasts. Further sub-analyses of lupus nephritis (LN) versus non-LN, demonstrated significantly reduced IL16 expression e.g., in Th1-like and double negative B cell subsets in LN. In parallel, SLE patients displayed increased pIL16 levels, and LN patients showed increased uIL16 which associated positively with disease activity SLEDAI-2K index and negatively with complement C4 levels and IL16+CD4+T-cell counts. In vitro, IL16 induced CXCR4 and CCR5 mediated migration of Th1-cells and attracted CD8+T cells via CXCR4, which was partially inhibited by IL16 blockade. We demonstrate reduced intracellular IL16 expression in SLE lymphocytes, with low IL16+CD4+T cell proportions in LN correlating with increased uIL16. Extracellular IL16 may drive Th1 and CD8+T cell infiltration, contributing to organ inflammation. IL16 blockade reduced T cell migration, highlighting its potential as therapeutic target.

We attempted to perform a comprehensive bioinformatics analysis on osteoarthritis (OA) based on the NKT-related genes and explore the clinically related critical genes. Differentially expressed genes (DEGs) and NKT-related genes from WGCNA were obtained using the dataset GSE114007, followed by intersection analysis to obtain NKT-related DEGs. Lasso regression, support vector machine, and random forest were performed to screen feature genes, followed by verification with receiver operator curves and a nomogram model. Protein-protein interaction network, gene set enrichment analysis was performed based on the four marker genes. Finally, the immune infiltration of 64 types of immune cells was analyzed between OA samples and normal samples. The significance of biomarkers was validated in clinical samples and OA mice models. A total of four NKT-related biomarker genes (CCNJ, CFI, PREX2, and SMIM13) were identified. These genes were all upregulated in OA samples. CFI exerted promising diagnostic value for OA with an AUC of 0.994 in GSE114007 training dataset and 0.98 in the validation dataset. A significantly negative correlation between CFI and NKT cells and a significantly positive correlation between CFI and conventional dendritic cells (cDC) were found. All the biomarkers were determined to be upregulated in OA patients by clinical samples. CFI knockdown significantly reduced DC infiltration and inflammation in the knee joints of OA mice models. CFI has potential value in the pathogenesis of OA and can be used as a candidate biomarker for OA diagnosis and treatment.

Post-transarterial chemoembolization (TACE) hypoxia plays a crucial role in hepatocellular carcinoma (HCC) progression. However, the effects of post-TACE hypoxia on HCC progression are not fully understood yet. This study aimed to elucidate the effects of post-TACE hypoxia-induced hypoxia-inducible factor-1α (HIF-1α)/WNT/β-catenin signaling on HCC progression. In this study, serum concentrations of soluble programed death ligand 1 (sPD-L1) and HIF-1α in HCC patients who underwent TACE were measured using enzyme-linked immunosorbent assay (ELISA). In vitro, WNT/β-catenin pathway activation was assessed by TOP/FOP luciferase activity, while HIF-1α-siRNA transfection was used to observe the interaction between HIF-1α and WNT/β-catenin. In vivo, mouse xenograft tumor models were used to examine the effects of programed death ligand 1 (PD-L1) on HCC progression and to verify the correlations among HIF-1α, WNT/β-catenin, and PD-L1. The mechanisms underlying hypoxia-induced PD-L1 overexpression were studied using chromatin immunoprecipitation (ChIP). We found that the median post-TACE serum sPD-L1 and HIF-1α concentrations in HCC patients were significantly higher compared to pre-TACE levels, with a significant correlation observed between sPD-L1 and HIF-1α. In vitro studies demonstrated that hypoxia promoted WNT/β-catenin activation and PD-L1 expression. HIF-1α silencing significantly inhibited WNT/β-catenin activation. In vivo, hypoxia-induced PD-L1 overexpression significantly promoted HCC progression. WNT/β-catenin activation increased PD-L1 promoter luciferase activity, and ChIP confirmed that LEF1 bound to the PD-L1 promoter in hypoxic hepatoma cells. Therefore, we concluded that the post-TACE hypoxia-induced activation of HIF-1α/WNT/β-catenin signaling could promote HCC progression by upregulating PD-L1 expression.

Since its discovery in the late 18th century, the role of vaccination in preventing death and disease has expanded across many infectious diseases and cancer. Key to our understanding of vaccine immunogenicity and efficacy is knowledge of the immune system itself. Inborn errors of immunity (IEI) represent a heterogeneous group of disorders characterized by impaired function of the immune system. Patients with IEI can have variable responses to vaccinations, depending on the nature and extent of the defect. Studies performed during the recent COVID-19 pandemic have brought unique insight into vaccine immunogenicity in individuals with IEI, knowledge that can be extended to the growing number of patients with secondary immunodeficiency arising from malignancy, organ transplantation, autoimmune conditions, and their treatments. In this review, we describe vaccine immunogenicity in IEI alongside their equivalent secondary immunodeficiencies and discuss what lessons can be learned about immunization strategies more broadly.