Central European Journal of Immunology最新文献

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.

The flow cytometry method could support physicians' decisions in the diagnosis and treatment monitoring of immunodeficient patients. Most clinical recommendations are focused on the search for alterations in T- and B-lymphocyte subsets, less commonly natural killer (NK) cells and granulocytes. While reference values for clinically meaningful lymphocyte subsets have been published ubiquitously among numerous countries, we have not found significant data for a population of adult Polish habitats; thus we determined reference values for T, B, and NK subsets according to sex and age. The female group showed a higher percentage of lymphocytes (CD45⁺⁺), T helper lymphocytes with a higher absolute count, as well as CD4/CD8 ratio, marginal zone-like B cells, class-switched B cells, and CD21^low B cells than the male group. The male group was found to have elevated percentages of naïve B lymphocytes, transitional B cells, and plasmablasts. A weak positive correlation with age was found among double positive T lymphocytes, natural killer T cells (NKT) lymphocytes, and CD21^low B cells. A negative correlation with age for double negative T lymphocytes, marginal zone-like B cells, and plasmablasts was noted. The results indicated the importance of creating distinct reference ranges regarding sex and age concerning immunophenotype.

Introduction: Hyperforin (HYP) has been reported to alleviate the inflammatory response. The purpose of this study was to examine the pharmacological effects of HYP on lipopolysaccharide (LPS)-induced inflammation and acute kidney injury (AKI).

Material and methods: In vitro and in vivo septic models were created using LPS-stimulated mice podocytes and LPS-injected mice. HYP (20 mg/kg/day) or antagomiR-21 (20 nM/0.1 ml; twice/week) was administered to mitigate LPS-induced AKI and podocyte apoptosis.

Results: HYP demonstrated potential as an NF-κB inhibitor, leading to enhanced survival rates in septic mice. Moreover, HYP directly hindered LPS-induced podocyte apoptosis and AKI. The underlying mechanism involves the modulation of LPS-induced transactivation of miR-21 by NF-κB. It was observed that excessive activation of the NF-κB/miR-21 signaling axis contributed to LPS-induced podocyte apoptosis and AKI. Additionally, the absence of miR-21 expression resulted in decreased LPS-induced podocyte apoptosis and amelioration of LPS-induced renal tubular injury.

Conclusions: The renoprotective effects of HYP were observed in septic mice through the inhibition of NF-κB/p65-mediated transactivation of miR-21. These findings suggest that targeting the NF-κB-miR-21 axis could be a potential therapeutic strategy for HYP in the prevention of AKI.

Esophageal cancer is considered one of the most significant challenges to public health worldwide. While various therapeutic options exist for esophageal cancer, including chemotherapy, radiotherapy, and surgery, several adverse effects of these medications have been reported. Therefore, a new generation of therapeutic lines should be applied to minimize complications. In this regard, immunotherapy is a novel approach that aims to kill tumor cells directly by targeting them. Specifically, monoclonal antibodies can target specific markers of esophageal cancer tumor cells, keeping other normal cells safe. Multiple monoclonal antibodies optimized for esophageal cancer, such as pembrolizumab, ramucirumab, trastuzumab, nivolumab, and ipilimumab, are available. On the other hand, esophageal cancer tumor cells express a specific inhibitory ligand and its receptor called programmed cell death, which can suppress T cell immune responses. This receptor provides an inhibitory signal, causing the highest expression of the PD-L1 ligand on tumor cells. The outcomes of this interaction lead to the suppression of the activation and function of T lymphocytes. Therefore, immunotherapy for esophageal cancer targeting the PD-1/PD-L1 pathway has shown a remarkable correlation with cancer care. This study presents a comprehensive review of the latest findings related to immunotherapy in esophageal cancer.

Eosinophilia is a feature of multiple conditions, both hematologic and non-hematologic, and may be associated with organ damage. The pathogenesis of eosinophilia can follow two distinct pathways. Primary eosinophilia is caused by a cell-intrinsic mechanism originating from clonal expansion of eosinophils through acquisition of a somatic mutation, such as FIP1L1-PDGFRA. In recent years, great progress has been made in the field of pathogenesis and molecularly targeted therapy of neoplastic eosinophilia. The diagnostic procedure should include, among other things, morphologic analysis of blood and bone marrow samples, cytogenetics and fluorescence in situ-hybridization tests to detect evidence of an acute or chronic myeloid or lymphoid disorder. Secondary eosinophilia follows a cell-extrinsic mechanism as a response to exogenous cytokines. In most clinical cases, peripheral blood eosinophilia is reactive and typically associated with non-hematological disorders such as infections, allergic conditions, connective tissue disorders, vasculitis, malignancy, or endocrinopathies. Nonetheless, the cause of most cases of hypereosinophilic syndrome remains unknown. In this article, we present a short review focused on differential diagnosis of eosinophilia and eosinophilic disorders. The diagnosis of eosinophilia is a challenge for physicians; thus this review may be useful in clinical practice.

Introduction: To explore the effects of anaerobic glycolysis on Jurkat T cell proliferation and clarify the possible mechanism via transcriptomic analysis.

Material and methods: The monocarboxylate transporter 1 inhibitor AZD3965 was used to target and block the transmembrane transport of lactate, thereby inhibiting anaerobic glycolysis in Jurkat T cells. Then, genes with differential expression between treated and untreated cells were detected by transcriptomic analysis, and constructs were generated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses as well as protein-protein interaction (PPI) network analysis were performed to explore the potential mechanism.

Results: Inhibition of anaerobic glycolysis reduced Jurkat T-cell proliferation. RNA sequencing identified 1723 transcripts that were differentially expressed, including 1460 upregulated genes and 263 downregulated genes. GO functional enrichment analysis showed that the differentially expressed genes were mainly involved in the biological processes of response to unfolded protein, response to topologically incorrect protein, and protein folding. KEGG pathway analysis of differentially expressed genes or hub genes from the PPI network analysis revealed enrichment in the estrogen signaling and PI3K-Akt pathways.

Conclusions: Anaerobic glycolysis contributes to the regulation of Jurkat T-cell proliferation. The underlying mechanism may involve the estrogen signaling pathway or PI3K-Akt signaling pathway as well as protein metabolism.

Introduction: The low-grade inflammation occurring in obese individuals leads to many diseases, including cardiovascular disease (CVD). Dietary patterns, food groups or nutrients in a well-balanced diet may reduce the level of pro-inflammatory markers and the risk of obesity-related morbidities. Our study aims to describe three cytokines in obese patients in relation to dietary habits, lifestyle and body composition.

Material and methods: Serum samples were collected from 84 obese adult volunteer subjects [body mass index (BMI) ≥ 30 kg/m²] to analyze the concentrations of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ). The subjects were tested by bioelectrical impedance analysis (BIA) and completed a three-day food diary and original questionnaire with the FFQ-6 food consumption frequency questionnaire.

Results and conclusions: Higher serum levels of IL-6 and IFN-γ were found in patients with atherosclerosis, but the group was too small for a reliable correlation. Subcutaneous but not visceral adipose tissue correlated positively with IL-6 levels. Dietary factors such as amount of sugars, including galactose and sucrose, in the diet and the frequency of consumption of sweet flavored dairy products correlated positively with the levels of IL-6 and TNF-α, while the frequency of alcohol consumption negatively correlated with the level of IL-6. The greater the frequency of sports, the higher was the level of IL-6. In obese individuals, the level of pro-inflammatory cytokines could predispose to atherosclerosis and is associated with dietary factors and lifestyle.

Introduction: Alternative in vitro tests that can be used instead of animal experiments are those that can most closely evaluate the biological activity of the drug of interest. For testing the potency of antivenom, these are the methods used to assess cytotoxicity. The aim of this study was to evaluate the most commonly used cytotoxicity methods for determining the protective potency of the antivenom Viekvin, which neutralizes Vipera ammodytes venom.

Material and methods: The selected methods are based on different biological mechanisms: MTT assay, based on the activity of cell oxidoreductase enzymes; crystal violet staining, based on the degree of cell adhesion; trypan blue staining, based on cell membrane permeability, and propidium iodide staining, based on measurement of nucleic acids of dead cells. The pro-apoptotic effect of the venom was also determined with annexin V staining.

Results: The IC₅₀ value of V. ammodytes venom obtained by these methods was very similar, while the EC₅₀ values differed significantly.

Conclusions: We concluded that the choice of the method used to measure the anticytotoxic anti-venom potency depends on the immunogenicity of the venom components that cause cell death; for each venom/antivenom pair, it is necessary to select the appropriate assay separately, and at present, none of the standard cytotoxic methods can be universally applied to determine antivenom potency.

Introduction: In adult-onset asthma, two major endotypes have been proposed: T2 with eosinophilia and non-T2 characterised by neutrophils and interleukin (IL)-17. The objective of the study was to examine the endotype marker profile in patients with severe asthma who were hospitalized for exacerbations, with a focus on differentiating between viral and non-viral triggers.

Material and methods: Forty-nine patients with asthma, admitted for exacerbations, and 51 healthy controls (HCs) were recruited. We further categorized the exacerbated asthma patients into two groups: non-viral infected (n = 38) and viral infected (n = 11) groups. Blood was drawn and a nasopharyngeal swab taken at the time of admission and eosinophil numbers, eosinophil cationic protein (ECP), immuno- globulin E (IgE), tryptase and viral infection were determined. Additionally, levels of IL-17, IL-33 and IL-31 were assessed.

Results: The majority of patients had adult onset asthma (age of diagnosis, 42.8 ±16.1) with a duration of 7.7 ±10.8 years, 24.5% being atopic. Patients had higher levels of eosinophils, ECP and IgE than healthy controls (eosinophils, p = 0.003; ECP and IgE, p = 0.0001). Immunohistochemistry confirmed eosinophils as a source of ECP. Tryptase (p = 0.0001), IL-17 (p = 0.0005), IL-31 (p = 0.0001) and IL-33 (p = 0.0002) were also higher in patients than controls. ECP correlated with tryptase (r = 0.08, p = 0.62). IL-17 showed the best correlation with other mediators, including ECP (r = 0.35, p = 0.24), tryptase (r = 0.69, p = 0.0001), IgE (r = 0.50, p = 0.0001), IL-33 (r = 0.95, p = 0.0001) and IL-31 (r = 0.89, p = 0.0001). IgE, IL-17, and IL-31 had a high AUC when differentiating those with severe and non-severe asthma. The group with exacerbated viral infection showed elevated levels of serum IL-17 and IL-31 compared to the non-infected group.

Conclusions: Patients with asthmatic exacerbations were found to have higher levels of both T2 and non-T2 inflammatory markers than healthy controls. In the study, levels of IgE, IL-17, and IL-31 differentiated between patients with severe and non-severe asthma. The last two cytokines were also able to distinguish between exacerbated asthma caused by viral infection and exacerbated asthma caused by non-viral infection.