Central European Journal of Immunology最新文献

Inflammatory bowel disease (IBD) is a group of diseases characterized by refractory and chronic inflammation of the bowel, which can be treated with biologics in clinical practice. Anti-tumor necrosis factor α (TNF-α) agents, which are among the most widely used biologics, alleviate the inflammatory activity in a variety of ways. Helicobacter pylori is a Gram-negative bacterium that colonizes the gastric mucosa, which could cause chronic inflammation and even induce gastric cancer. However, it has been suggested that H. pylori has a potential protective role in IBD patients. Yet there has been limited research on the mechanisms of the effect of H. pylori infection in IBD patients, and whether there is an interaction between H. pylori and anti-TNF-α agents. This review aims to summarize the possible mechanisms of H. pylori and anti-TNF-α agents in the development and treatment of IBD, and to explore the possible interaction between H. pylori infection and anti-TNF-α agents.

Introduction: Apurinic/apyrimidinic endonuclease 1 (APEX1) is a protein with elevated expression in synovial fluids from rheumatoid arthritis (RA) patients. However, its role in RA pathogenesis remains unexplored. This study investigated the influence of APEX1 on inflammatory pathways in fibroblast-like synoviocytes (FLS) isolated from RA patients.

Material and methods: FLS from RA patients (n = 5) were stimulated with recombinant tumor necrosis factor α (TNF-α) and interleukin (IL)-17. Subsequently, cells were treated with recombinant APEX1, and assessments were made on reactive oxygen species (ROS) production and mitochondrial membrane potential. Additionally, mRNA levels of IL-1 family members were quantified. Cell migration was evaluated through Transwell chamber assays, and levels of key secreted inflammatory cytokines were measured via enzyme-linked immunosorbent assay (ELISA).

Results: The results demonstrated that APEX1 significantly reduced mitochondrial-specific ROS expression and restored mitochondrial membrane potential in TNF-α/IL-17-stimulated RA FLS. Furthermore, APEX1 treatments attenuated TNF-α/IL-17-induced activation of p38 MAPK, NF-κB, and PI3K 110 δ signaling pathways. Similarly, APEX1 significantly diminished TNF-α/IL-17-induced expression of inflammatory cytokines, including IL-1 family members, IL-6, IL-8, and vascular endothelial growth factor (VEGF). Notably, APEX1 downregulated cell migration of TNF-α/IL-17-treated RA FLS via inhibition of matrix metalloproteinase 3 (MMP3).

Conclusions: These findings collectively underscore the role of APEX1 as a key mediator of cytokine-amplified migration, modulating ROS and MMP3 in RA FLS, thus supporting its potential as a therapeutic target in RA treatment.

Introduction: The presence of patients with latent tuberculosis infection (LTBI) has fueled the tuberculosis pandemic. We aimed to investigate the immune status of NK cells in LTBI patients.

Material and methods: Twenty-one LTBI patients, 25 active pulmonary tuberculosis (APTB) patients and 25 healthy controls (HCs) participated in our research. The markers of NK cells were detected by flow cytometry.

Results: The absolute number of circulating CD56bright and CD56dim NK cells in LTBI patients was higher than that of APTB patients, but the frequency of HLA-DR+ CD56bright NK cells was significantly lower than that of HCs and APTB patients. Also, LTBI patients with CD56bright NK cells had intracellular levels of granzyme B that were as significantly elevated as those with APTB patients, but the levels of granzyme A and perforin were reduced. Meanwhile, the frequencies of CXCR3+ NK cells, CXCR3+ CD56bright and CXCR3+ CD56dim NK cells were significantly lower in LTBI patients.

Conclusions: Circulating CD56bright NK cells exerted a significant role in maintaining immune balance in LTBI patients. An elevated frequency of granzyme B+ CD56bright NK cells and a reduced frequency of perforin+ CD56bright NK cells were effective in differentiating LTBI patients from HCs.

Introduction: Rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) are serological markers used for diagnosing rheumatoid arthritis (RA), an autoimmune disease characterized by inflammatory joint damage. However, there is a subset of RA patients who test negative for both RF and ACPA, known as seronegative rheumatoid arthritis (SNRA).

Material and methods: The levels of serum markers were examined in both clinical samples and a rat model of type II collagen-induced RA (CIA). The effect of interleukin 9 (IL-9) on RA was investigated using recombinant rat IL-9 (rrIL-9), anti-rat IL-9 neutralizing monoclonal antibody (mAb), and control IgG antibody in the CIA rat. The severity of arthritis was assessed. Treg and Th17 cells, M1 and M2 macrophages, and inflammatory cytokine levels were analyzed.

Results: We observed higher levels of IL-9 in clinical samples from SNRA patients compared to the normal group. Rat models of CIA exhibit increased arthritis scores, weight loss, paw swelling, and severe joint damage. IL-9 was the most sensitive serum marker for the diagnosis of RA in serum assays of CIA rats. IL-9 increased arthritis scores and cartilage damage, whereas treatment with IL-9 inhibitors produced the opposite effect. IL-9 inhibitors promoted Treg/Th17 homeostasis, decreased M1 macrophages, increased M2 macrophages, and decreased levels of inflammatory cytokines in joint tissues.

Conclusions: These results suggest that IL-9 has potential as a diagnostic marker for SNRA. Inhibition of IL-9 could reduce the severity of arthritis in CIA rats by ameliorating inflammation and modulating the Treg/Th17 immune balance, M2 and M1 macrophage activation.

Introduction: Flow cytometry immunophenotyping is a common laboratory technique for evaluating lymphocyte subpopulations. Its result remains an important diagnostic tool in various medical fields. Cytometric tests are performed in many laboratories, making the comparability between different devices using the same method an important aspect. We aimed to compare the results of lymphocyte immunophenotyping (lymphocytes B, T, Th and Tc, NK cells) between two different flow cytometers.

Material and methods: The study included 93 patients of the Children's Teaching Hospital of the Medical University of Warsaw and 9 Multi-Check control results. The method of lymphocyte subpopulation assessment was based on fluorescent flow cytometry immunophenotyping, using a BD Multitest 6-color TBNK kit (Becton Dickinson). We compared BD FACSCanto II and BD FACSLyric analysers (Becton Dickinson). For data analysis, we used Spearman's rank correlation, Bland-Altman plot and Passing-Bablok regression.

Results: Spearman's rank correlation showed a strong interrelation for all analysed parameters (0.808-0.985). In the Passing-Bablok regression analysis, all examined parameters showed linear dependence with the slope values close to 1 (0.940-1.134). Bland-Altman coefficient values were within the range of 2.94-8.62% with half of them being above 5% (T, Tc, Th, B, NKT absolute values and B percentage values).

Conclusions: The results from both cytometers can be considered equivalent, but it should be noted that one of the statistical methods showed some deviations, presumably primarily due to the evaluators' different gating techniques. The training of specialists performing these tests requires more attention.

Introduction: Gliomas are the most common malignant brain tumors, with complicated etiology and poor prognosis. However, there is still a lack of specific biomarkers for the diagnosis, treatment and prognosis assessment for glioma patients. Hence, the purpose of this study was to screen biomarkers for prognostic assessment and therapeutic interventions in gliomas.

Material and methods: We utilized The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases to investigate the role of colony-stimulating factor 3 receptor (CSF3R) in glioma. Data analysis was conducted using R, GEPIA 2, TISCH and DepMap.

Results: CSF3R was up-regulated in glioma and associated with the clinical pathological features of the patients. Kaplan-Meier survival analysis indicated a significant association between the expression of CSF3R and prognosis in patients. Univariate and multivariate Cox analyses revealed that patients with high expression of CSF3R have a worse prognosis, and the expression of CSF3R was an independent prognostic factor in gliomas. The nomogram constructed based on the expression of CSF3R demonstrated lower 1-, 3-, and 5-year overall survival (OS) in patients with high CSF3R expression. The biological functional analysis of CSF3R demonstrated its association with various immune regulatory signals. Furthermore, CSF3R was linked to the expression of immune checkpoints and resistance to immunotherapy. Notably, CSF3R was predominantly detected in monocytes/macrophages.

Conclusions: Our study suggested that CSF3R might potentially function as an independent prognostic factor for glioma and hold promise as a biomarker and target for immunotherapy in glioma.

Introduction: Periodontitis, a chronic inflammatory disease associated with dental biofilm, poses a significant threat to oral health. This study explores the roles of interleukin 1β (IL-1β) and nesfatin-1 in periodontal diseases, aiming to contribute to the molecular understanding of their pathogenesis.

Material and methods: A diverse cohort of 62 participants was recruited, spanning ages 20 to 60, and categorized into healthy, gingivitis, and periodontitis groups. Clinical measurements, including plaque index, gingival index, probing pocket depth, and bleeding on probing, were conducted. Gingival crevicular fluid (GCF) samples were collected for IL-1β and nesfatin-1 analysis using enzyme-linked immunosorbent assay (ELISA). Statistical analysis employed Kruskal-Wallis and Spearman correlation tests.

Results: Significant differences in oral hygiene habits were observed among groups, particularly in the 40-60 age range. Clinical indices showed variations, with the highest IL-1β levels in the periodontitis group and the lowest nesfatin-1 levels. Correlation analysis revealed positive associations between IL-1β, nesfatin-1, and oral indices.

Conclusions: While providing valuable insights, we acknowledge this study's limitations, including a cross-sectional design and a specific age range. Future research should employ longitudinal designs and larger cohorts, and explore broader inflammatory markers, genetic influences, and confounding variables for a more comprehensive understanding of periodontal diseases. The findings underscore the complex interplay between inflammatory markers and periodontal health.

Introduction: To explore the progression patterns of advanced hepatocellular carcinoma (HCC) in patients treated with a combination of local therapies, targeted drugs, and PD-1/PD-L1 inhibitors.

Material and methods: A retrospective study involving 86 patients with Barcelona Clinic Liver Cancer stage C HCC was conducted between August 2018 and April 2022. All patients received local therapy, targeted drugs, and PD-1/PD-L1 inhibitors. Disease progression was evaluated using computed tomography or magnetic resonance imaging after combination therapy. Peripheral blood immune cells were analyzed using flow cytometry.

Results: For intrahepatic progression, the median time to first progression was 5.3 months in 60 patients (95% confidence interval (CI): 2.3-7.1 months), and the median time to second progression was 9.3 months in 40 patients (95% CI: 4.8-11.8 months, p < 0.0001). For extrahepatic progression, the median time to first progression was 5.8 months in 61 patients (95% CI: 1.6-8.4 months), and the median time to second progression was 8.7 months in 39 patients (95% CI: 4.5-10.9 months, p < 0.0001). The common sites of extrahepatic progression are the lymph nodes and lungs. The percentages of PD-1+ cells gradually decreased after combination treatment but then gradually increased at follow-up in extrahepatic progression. The percentages of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells and CD16+CD56+ cells exhibited different trends in intrahepatic and extrahepatic progression.

Conclusions: After combination treatment, patients with advanced HCC exhibit different characteristics of disease progression and composition of peripheral blood immune cells. Lymph nodes and lungs were the most susceptible sites for disease progression.

Introduction: The study aimed to investigate the complicating thyroid dysfunction situation in patients with rheumatoid arthritis (RA) and to analyze the related risk factors of thyroid dysfunction in RA patients.

Material and methods: The retrospective analysis of the clinical data and laboratory examinations of 290 cases of RA and 200 healthy individuals undergoing the physical examination was carried out. The thyroid function, anti-thyroid antibodies, and routine laboratory test items were measured. The RA disease activity score (DAS28) was determined in RA patients. Logistic analysis was used to identify risk factors associated with thyroid dysfunction in RA patients.

Results: The detection rate of RA combined with thyroid dysfunction was 30.0%, which was higher than in the control group (7%, 14 cases). In the thyroid function test, levels of total triiodothyronine (T3) and free triiodothyronine (FT3) were lower, while thyrotropin (TSH), antithyroid peroxidase antibody (TPOAb), and antithyroglobulin antibody (TgAb) were higher in the RA group. There was a difference in hemoglobin (HGB) and total cholesterol (TC) in RA patients with and without abnormal thyroid function.

Conclusions: Rheumatoid arthritis patients are more prone to develop thyroid dysfunction than healthy individuals, especially hypothyroidism. HGB and TC were correlated with thyroid hormones and antibodies and were risk factors correlated with thyroid dysfunction in RA patients. Clinical work should pay full attention to changes in thyroid function in patients with RA.