BMC Immunology最新文献

Background: The human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a chronic inflammatory neurodegenerative disease characterized by leukocyte infiltration in the spinal cord. T-lymphocytes are the most important targets of HTLV-1 infection, but monocytes are also infected. Monocytes from HTLV-1-infected individuals exhibit important functional differences compared to cells from uninfected donors. Here, we investigated the effects of cell-cell physical contact and/or secreted factors of HTLV-1-infected cells in monocyte activation and differentiation.

Methods: The THP-1 human monocytic cell line was co-cultured with a human cell line transformed by HTLV-1 (MT-2) for 6 days. To determine the effects of co-culturing HTLV-1-infected cells in THP-1 monocytes cells were characterized by flow cytometry, immunofluorescence microscopy, and real-time PCR. Computational analysis of published transcriptomic datasets was realized to compare molecular profiles of macrophages and mononuclear cells from HTLV-1 carriers.

Results: Co-culture of monocytes with HTLV-1-infected cells induced macrophage differentiation and upregulation of typical macrophages-associated molecules (HLA-DR, CD80, and CD86), increased cytokine (TNFα, IL-6, and IL-1β) levels and their coding genes expression. Consistently, published transcriptomic datasets showed changes in important genes associated with inflammation during HAM/TSP in patients. The presence of HTLV-1-infected cells in the culture also induced significant upregulation of Interferon Stimulated Genes (ISG), indicating viral infection. Monocyte activation and differentiation into pro-inflammatory macrophages occurred in a cell-to-cell contact-independent manner, suggesting the role of factors secreted by infected cells.

Conclusions: Together, our results indicated that HTLV-1-infected cells induced monocyte differentiation into macrophages inflammatory, predominantly.

Background: Sepsis remains a leading cause of global morbidity and mortality, yet early diagnosis is hindered by the limited specificity and sensitivity of current biomarkers.

Aim: The aim of this study was to identify lncRNAs that play a key role in sepsis and provide potential biomarkers for the diagnosis and treatment of sepsis.

Methods: Transcriptomic data from sepsis patients were retrieved from the Chinese National Genebank (CNGBdb). Differential expression analysis identified 2,348 LncRNAs and 5,125 mRNAs (|FC|≥2, FDR < 0.05). Weighted gene co-expression network analysis (WGCNA) and meta-analysis were applied to screen core genes. Gene set enrichment analysis (GSEA) explored functional pathways, while single-cell sequencing and qPCR validated cellular localization and expression patterns.

Results: WGCNA identified three key genes: LINC02363 (LncRNA), DYNLT1, and FCGR1B. Survival and meta-analyses revealed strong correlations between these genes and sepsis outcomes. GSEA highlighted LINC02363's involvement in "herpes simplex virus type 1 infection," "tuberculosis," and ribosome pathways. Single-cell sequencing showed FCGR1B's broad distribution across immune cells, while DYNLT1 localized predominantly in macrophages. qPCR confirmed significant upregulation of LINC02363 (p < 0.01), FCGR1B (p < 0.05), and DYNLT1 (p < 0.05) in sepsis patients compared to controls.

Conclusion: LINC02363 may serve as a new biomarker for the diagnosis and treatment of sepsis.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, significant challenges have been encountered in managing patients with chronic diseases. This study aimed to evaluate the effects of the pandemic on follow-up and treatment adherence in patients receiving immunoglobulin replacement therapy (IRT).

Methods: A study examining the changes in IRT application methods was conducted between March 2020 and September 2021. An online message line, under the control of nurses and doctors, was established for our patients, and their usage rates for this communication system were recorded.

Results: A total of 169 patients, 93 males and 76 females, were included in the study. Among the patients, 124 (73.4%) received intravenous immunoglobulin (IVIG), and 45 (26.6%) received subcutaneous immunoglobulin (SCIG) treatment. Male sex was more common in both the IVIG and SCIG groups. Although all patients in the subcutaneous treatment group continued the treatments regularly, this rate was 80.6% in the IVIG group. During the pandemic, 26 patients switched from IVIG to SCIG treatment. Furthermore, 24 patients interrupted immunoglobulin treatment for various reasons. Patients who received subcutaneous treatment took a long break from their hospital controls, although they applied them properly at home. Routine immunoglobulin trough values were measured in only 17 (37.7%) patients who were on SCIG. In the presence of symptoms, 100% of SCIG patients contacted the remote medical team via the online message line, compared to 48.3% of IVIG patients.

Conclusion: During the pandemic, the route of immunoglobulin treatment should be individualized based on each patient's characteristics and expectations. Telehealth services have emerged as a crucial tool for monitoring patients with chronic disorders, facilitating effective communication and personalized care.

Background: Peripheral blood mononuclear cells (PBMCs) are valuable biomarkers, providing crucial insights into the patients' immune system. Reliable biobanking of PBMCs is essential to minimize heterogeneity. In multicenter trials, blood sample transportation to central laboratories can increase the time between blood collection and PBMC isolation. This study evaluated the effect of prolonged blood hold time on PBMC viability and cytotoxicity.

Methods: From July 2021 to May 2023, 104 patients with early HER2-positive breast cancer were enrolled in the NeoOn trial, of whom 49 patients were included in this subproject. PBMCs were isolated ≤ 6 hours (h) or ≥ 20 h after blood collection. PBMC yield and viability were determined using the LUNA-II Automated Cell Counter. Flow cytometry was used to quantify in vitro cytotoxicity, the percentage of natural killer (NK) and T cells, as well as apoptotic and necrotic cells.

Results: Isolating PBMCs ≥ 20 h resulted in a higher cell yield, but lower NK cell viability compared to PBMCs ≤ 6 h. PBMCs ≥ 20 h were less robust to thawing and showed higher loss during recovery. Compared to PMBCS ≤ 6 h, PBMCs ≥ 20 h exhibited lower antibody-mediated cytotoxicity (p ≤ 0.0001) and antibody-dependent phagocytosis (p < 0.0051). While the percentage of T and NK cells and the T cell viability remained unaffected by hold time, the percentage of apoptotic NK cells was higher for PBMCs ≥ 20 h (41.0 ± 12.9% vs. 23.8 ± 13.4%; p = 0.0364).

Conclusions: Extended blood storage time caused increased apoptosis and necrosis of NK cells, adversely affecting PBMC quality and reducing NK cell related functionality. Hence, blood hold time should be minimized to maintain PBMC integrity and NK cell functionality for in vitro biomarker assays.

Trial registration: Trial registration number: EudraCT 2020-001943-21. Date of registration: December 29th 2020.

Background: Hepatocellular carcinoma (HCC) is the most frequent kind of liver cancer with high morbidity and mortality rates worldwide. Altered expression of BUB1 (budding uninhibited by benzimidazole 1) gene leads to chromosome instability and aneuploidy. This study investigated the expression of BUB1 and its prognostic value as well as its correlation with immune cell infiltration and immune checkpoints in HCC.

Results: Using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, we found that BUB1 was up-regulated in HCC, thus prompting us to validate this observation by immunohistochemistry on 57 HCC paraffin embedded tissues from Wuxi No.2 People's Hospital. Kaplan-Meier survival analysis revealed that HCC patients with high BUB1 expression had shorter overall survival (OS) time as well as progression-free interval (PFI), and disease-specific survival (DSS) time compared to the patients with low BUB1 expression. Besides, STRING database showed that the top 10 co-expression genes were mainly involved in the regulation of cell division during the mitosis. Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that BUB1 had a connection to cancer related pathways. Lastly, The Tumor Immune Estimation Resource (TIMER) analysis found that BUB1 was positively related to immune cell infiltration and some immune checkpoint gene in HCC.

Clinical trial number: Not applicable.

Conclusions: Our present study demonstrated that BUB1 is a potential prognostic biomarker, and BUB1 may play a role in the tumor immune microenvironment in HCC.

Background: Moyamoya disease (MMD) is increasingly recognized as being influenced by chronic inflammation, with circulating immune cells playing a role in its progression. However, research on the immune characteristics of different MMD subtypes is limited. This study aims to compare the peripheral immune profiles of ischemic and hemorrhagic MMD patients.

Methods: Peripheral immune profiles were analyzed using transcriptome sequencing and mass cytometry. Data preprocessing was followed by functional and gene set enrichment analyses, as well as the construction of immune-related gene sets and protein-protein interaction networks. High-dimensional data analysis was performed using the PhenoGraph and t-SNE algorithms.

Results: The study involved 9 ischemic and 6 hemorrhagic MMD patients for transcriptome analysis, and 20 ischemic and 16 hemorrhagic patients for mass cytometry. Hemorrhagic MMD patients exhibited upregulated genes associated with inflammation, hypoxia, and bacterial responses and downregulated genes related to immune response regulation. The results of mass cytometry analysis showed that, compared to ischemic MMD, patients with hemorrhagic MMD had reduced CD3 expression levels in T cells and their specific subsets, as well as impaired chemotactic capacity of DPT cells. The function of the B03 subset in B cells was diminished, while the proportion of NK cells increased and that of monocytes decreased. Additionally, the proportions of the D03 and D07 subsets in dendritic cells (DCs) were elevated.

Conclusions: This study reveals distinct immune profiles in ischemic and hemorrhagic MMD, emphasizing the need for subtype-specific therapeutic strategies.

Background: Inflammatory bowel disease (IBD) has become a global healthcare issue, with its incidence continuing to rise, but currently there is no complete cure. Xylitol is a widely used sweetener in various foods and beverages, but there is limited research on the effects of xylitol on IBD symptoms.

Aim: Study on the effect of oral xylitol in improving intestinal inflammation and damage in IBD mice, further explore the mechanism of xylitol in alleviating IBD symptoms using intestinal microbiota and non-targeted metabolomics techniques.

Methods: An IBD mouse model was induced using sodium dextran sulfate (DSS). After 30 days of oral administration of xylitol, we assessed the disease activity index (DAI) scores of mice in each group. The expression levels of inflammatory factors in the colon tissues were measured using qPCR. Additionally, we examined the damage to the intestinal mucosa and tight junction structures through HE staining and immunohistochemical staining. Finally, the alterations in the gut microbiota of the mice were analyzed using 16S rDNA sequencing technology.The production of three main short-chain fatty acids (SCFAs, including acetate, propionic acid and butyric acid) in feces and the changes of serum metabolomics were measured by non-targeted metabolomics techniques.

Results: The findings indicated that xylitol effectively mitigated weight loss and improved the DAI score in mice with IBD. Moreover, xylitol reduced the expressions of Caspase-1, IL-1β, and TNF-α in the colon tissue of the mice, and increased the expressions of ZO-1 and occludin in intestinal mucosal. Xylitol could enhance the variety of intestinal bacteria in IBD mice and influenced the abundance of different bacterial species. Additionally, metabolomic analysis revealed that oral xylitol increased the levels of three main SCFAs in the feces of IBD mice, while also impacting serum metabolites.

Conclusions: Our findings suggest that xylitol can help improve IBD symptoms. Xylitol can improve the intestinal flora of IBD mice and increase the production of SCFAs to play an anti-inflammatory role and protect the mucosal tight junction barrier. These discoveries present a fresh prophylactic treatment of IBD.

Clinical trial number: Not applicable.

Background: Anti-interferon-γ autoantibodies (AIGAs) syndrome is a recently recognized adult-onset immunodeficiency syndrome. Serum Immunoglobulin E (IgE) is increased in AIGAs syndrome, but the role of serum IgE levels in the clinical features and disease outcomes of AIGAs syndrome is not clear.

Methods: We retrospectively enrolled 163 patients diagnosed AIGAs syndrome with serum IgE examined at baseline from 2021 to 2024 and compared the clinical features between Group A (serum IgE level ≤ 212 IU/mL) and Group B (serum IgE level > 212 IU/mL). Multivariable logistic regression method was used to explore the risk factors associated with disease outcomes.

Results: 163 patients were included in this study, of whom 97 patients were in Group A (serum IgE level ≤ 212 IU/mL) and 66 patients in Group B (serum IgE level > 212 IU/mL). Group B showed higher number of infectious episodes, elevated levels of erythrocyte sedimentation rate (ESR), CD3 + T cells, immunoglobulin G (IgG), IgA, and globulins (GLB), shorter progression-free survival (PFS), and increased exacerbation numbers. Group B exhibited a higher incidence of fatigue, dyspnea, loss of appetite, rash, moist rales, hepatomegaly, and splenomegaly. Skin, bone marrow and spleen involvements were more common in Group B. IgE demonstrated correlations with IgG, GLB, Albumin (ALB), Eosinophils (EOS), IgG4, and ESR. During the follow-up, Group B exhibiting higher number of exacerbations compared to Group A (P < 0.0001). Multivariable Cox regression analysis revealed that High AIGAs titers (hazard ratio [HR], 2.418, 95% confidence interval [CI]1.037-5.642, P = 0.041), WBC > 22.52 × 10⁹cells/L (HR2.199, 95%CI1.194-4.050, P = 0.012) were independent risk factors of disease exacerbation. Glucocorticoid treatment was commonly used in patients with AIGAs syndrome who had elevated IgE levels and skin involvement, demonstrating efficacy in improving condition.

Conclusions: Elevated serum IgE levels are associated with more severe clinical features in AIGAs syndrome, including increased infectious episodes, elevated inflammatory markers/immune markers, and multi-organ involvement, particularly skin. IgE serves as a marker of skin involvement and may indicate a potential response to glucocorticoid treatment.

Recent research advancements have enhanced our understanding of the lymphatic system in the eye and nasal region and its involvement in health and disease. The eye is an anatomical extension of the central nervous system and was previously believed to be devoid of lymphatic structures, except for the conjunctiva. However, Lymphatic vessels have been recently identified in the cornea (under pathological conditions), limbus, ciliary body, extraocular muscles, conjunctiva, lacrimal gland, optic nerve sheath, and lymphoid structures in the choroid and Schlemm's duct. These novel findings have significant implications in eye disease treatment; however, the mechanisms by which they preserve immune balance in the eye and eliminate metabolic waste and inflammatory cells remain nebulous. Furthermore, connections have been observed between ocular and nasal lymphatic vessels via the lymphatic network accompanying the nasolacrimal duct. The nasal lymphatic vessels are the primary pathway for cerebrospinal fluid drainage and a new route for drug delivery and treatment of brain-related diseases. This review provides an overview of recent advancements in understanding the structure and function of the ocular and nasal lymphatic systems and their association with cerebrospinal fluid drainage and various diseases.

Background: Hymenoptera venom allergy is a significant allergic reaction that affects a substantial proportion of adults. Accurate diagnosis of this allergy using venom extracts is challenging due to molecular cross-reactivity. Pure recombinant allergens offer a promising solution to identify the specific venom responsible for allergic reactions. This study aimed to produce recombinant phospholipase A5 (Ves v 5) from yellow jacket venom and evaluate the pattern of bee venom sensitization in a group of sensitive patients.

Methods and results: A total of seven individuals, including four sensitive and three non-sensitive participants, were recruited for this study. Blood samples were collected, and serum was isolated to assess susceptibility to bee venom and recombinant allergens. Expression of Ves v 5 in Escherichia coli resulted in the production of soluble proteins, which were subsequently purified through affinity chromatography. The functionality of the recombinant allergens was evaluated through enzymatic and biophysical analyses, such as dot blot and SDS‒PAGE tests. The diagnostic relevance of Ves v 5 was further investigated using ELISA-based analyses of sera from yellow jacket venom-sensitized patients. Successful production of soluble Ves v 5 in Escherichia coli was achieved. The recombinant Ves v 5 exhibited distinct biochemical and functional characteristics. Evaluation of IgE reactivity in sera from patients underscored the importance of Ves v 5 in hymenoptera venom allergy.

Conclusions: Our findings suggest that recombinant allergens can serve as an alternative to natural extracts for diagnostic purposes. Furthermore, allergen-specific immunotherapy holds the potential to enhance efficiency and specificity in the treatment of hymenoptera venom allergy.