Allergologia et immunopathologia最新文献

Background: Osteoarthritis (OA) is the most usual joint disease, which affects the life of patients and causes them seriously physical pain. Amygdalin, the main active pharmaceutical ingredient in Semen Armeniacae Amarum, has anti-inflammatory, anti-oxidation, and immunomodulatory impacts. However, the regulatory functions of Amygdalin in OA progression keep indistinct and need further investigations. This study is aimed to probe the regulatory influences and associated pathways of Amygdalin in OA development.

Methods: The cell viability was confirmed through CCK-8 assay. The levels of PGE2, TNF-α and IL-6 were detected through ELISA. The ROS level was examined through DCF staining. The levels of MDA, SOD and GSH were measured through the commercial kit. The protein expressions were evaluated through western blot.

Results: Firstly, it was demonstrated that Amygdalin can refrain IL-1β-evoked inflammation in chondrocytes. Next, Amygdalin repressed IL-1β-triggered oxidative stress in chondrocytes. Moreover, Amygdalin inhibited IL-1β-mediated ECM degradation in chondrocytes. Lastly, it was revealed that Amygdalin accelerated the Nrf2 pathway and suppressed the NF-κB pathway.

Conclusion: Amygdalin attenuated IL-1β-stimulated chondrocyte damage through the Nrf2/NF-κB pathway, thereby ameliorating OA progression. This finding hinted that Amygdalin may be one promising drug for OA treatment.

Objective: This study aimed to determine the frequency of neutropenia in patients with common variable immunodeficiency (CVID) and investigate its relationship with disease prognosis.

Methods: Data from 84 patients diagnosed with CVID and followed between 2019 and 2024 at the Department of Adult Clinical Immunology and Allergy, Necmettin Erbakan University, were retrospectively reviewed. Patients were divided into two groups based on the presence or absence of neutropenia. Demographic data, clinical findings, laboratory parameters, and survival rates were compared. Statistical analyses included the Mann-Whitney U test, the Chi-square test, and the Kaplan-Meier survival analysis.

Results: A total of 84 patients diagnosed with CVID were included in the study, with a median age of 38 years (range, 20-79 years). Of the participants, 48.8% were females (n = 41). Neutropenia was observed in 28.5% of patients (n = 24). The most common presenting complaints included autoimmune cytopenias, such as anemia and thrombocytopenia. Compared to non-neutropenic patients (n = 60), those with neutropenic CVID had a significantly higher mortality rate (33.3% vs 6.7%, P = 0.004). According to Kaplan-Meier survival analysis, the 8-year survival rates were 57.5 and 92.5% for neutropenic and for non-neutropenic CVID patients (p < 0.001), respectively.

Conclusion: This study suggests that neutropenia in CVID patients may be more than just a hematological issue; it could also serve as an important clinical marker associated with increased mortality. Recognizing and closely monitoring neutropenia is essential for effective CVID management.

Introduction: Anaphylactic reactions represent a serious risk for children within the school environment. It is essential that teachers are prepared to respond quickly and effectively. The objective of this study was to evaluate the ability of trainee teachers to administer adrenaline, both intramuscularly and intranasally, in a simulated anaphylactic shock scenario.

Material and methods: This quasi-experimental pilot study included 23 undergraduate students in Primary Education who received training in managing severe allergic reactions. They were evaluated twice in a simulated anaphylaxis scenario. In the first test, participants chose the adrenaline device (intramuscular or intranasal). In the second, they repeated the scenario using the alternative device. Variables related to the execution of each step and the time required were recorded.

Results: More than 80% of participants correctly completed all steps with the intranasal device. However, greater difficulties appeared with the intramuscular autoinjector, particularly maintaining it in position for at least 5 seconds and massaging the area afterward, which only 20% completed. The correct compliance rate was significantly higher with the intranasal device (100% vs. 71.43%, p = 0.012), and the administration time was shorter (p = 0.022). Initially, almost 70% chose the intramuscular autoinjector, but after testing both devices, 60.9% preferred the intranasal route.

Conclusions: A brief theoretical-practical training session is effective in training future teachers to respond appropriately to anaphylaxis in schools. Participants preferred the intranasal route for its simplicity and lower invasiveness.

Background: Adult immunoglobulin E (IgE)-mediated food allergy (FA) is increasingly recognized, yet it has remained under-characterized, compared with pediatric FA. We described clinical features, diagnostic profiles, predictors of severe reactions and explored a pragmatic total IgE cut-off in an adult cohort.

Method: We retrospectively reviewed 423 consecutive adults evaluated for suspected IgE-mediated FA at a tertiary center. Demographics, comorbid atopy, index culprit foods, diagnostic testing (skin prick/prick-to-prick, serum-specific IgE, component-resolved diagnostics), laboratory parameters, reaction severity (Brown grade severity), and adrenaline autoinjector (AAI) prescribing were extracted. Group comparisons used χ²/Fisher's exact, t-test, or Mann-Whitney U tests. Receiver operating characteristic analysis assessed the discriminative value of total IgE for confirmed FA. Variables associated with Brown grade 3 severity were examined by multivariable logistic regression.

Results: FA was confirmed in 79/423 patients (18.7%). Median age was 39.2 years; 71.4% were females. Frequent implicated groups were meat (23.9%), fruit (23.4%), nuts (22.5%), and vegetables (19.4%). Atopy was present in 46.1%; sensitization to mites and pollens occurred in 38.3% and 25.1%, respectively. Compared to non-confirmed cases, confirmed FA showed higher proportions of asthma, non-steroidal anti-inflammatory drug allergy, moderate/severe reactions (Brown grades 2-3 severity), atopy, mite/pollen sensitization, latex-fruit and pollen-fruit syndromes, AAI prescription, and food-dependent exercise-induced anaphylaxis (all P < 0.05). Eosinophil count/percentage and total IgE were also high (all P < 0.05). Total IgE ≥110.5 IU/mL predicted confirmed FA with 64.6% sensitivity and 59.7% specificity (area under curve 0.634; 95% confidence interval [CI]: 0.561-0.706; P = 0.001). In multivariable analysis, the absence of rhinitis and fish/seafood allergy, and the presence of atopy were independently associated with Brown grade 3 severity (model accuracy 84.4%). Overall, AAIs were prescribed in 38.1%, more often when FA was confirmed (66.7% vs 31.7%).

Conclusions: Adult FA in a real-world tertiary cohort is clinically heterogeneous and clusters with respiratory atopy. A total IgE threshold of 110.5 IU/mL offers modest discrimination and should complement, not replace, history and allergen-specific testing. Rhinitis, fish/seafood allergy, and lack of atopy identify patients at higher risk of severe reactions and may guide risk stratification and AAI prescribing.

ST-elevation myocardial infarction (STEMI) involves the complete blockage of a coronary artery, leading to severe cardiac damage and high mortality. miR-1 promotes cardiomyocyte apoptosis by downregulating the anti-apoptotic protein BCL2, while miR-126-5p negatively regulates PIK3R2 by activating the PI3K/Akt pathway. The expression of these miRNAs correlates with BCL2, PIK3R2, and high-sensitivity cardiac troponin T (hs-cTnT) in patients and controls, highlighting their role in apoptosis and myocardial injury. This study aimed to compare serum levels of miR-1, BCL2, microRNA-126-5p (miR-126-5p), Phosphoinositide-3-Kinase Regulatory Subunit 2 (PIK3R2), and cTnT in patients and controls. The association of miR-1 with BCL2 and miR-126-5p with PIK3R2 in STEMI patients was analyzed using ELISA and statistical analysis. Results showed a substantial increase in BCL2 levels in STEMI patients (128.01 ± 137.19) compared to controls (40.65 ± 20.92), and a decrease in miR-1 levels in STEMI patients (31.35 ± 68.89) compared to controls (43.43 ± 31.28). Similarly, the PIK3R2 and miR-126-5p levels among cases and controls were 228.55 ± 127.4 and 0.17 ± 0.32, respectively, showing a significant difference between patients and controls. Statistical analysis revealed that the expression levels of miR-1 and miR-126-5p are significantly different between controls and patients (p-value < 0.05), demonstrating a strong association with the prognosis of ST-elevation myocardial infarction. Moreover, a strong correlation was observed between BCL2 levels and PIK3R2 levels (p-value < 0.05) among STEMI patients. These results establish a profound diagnostic profile for STEMI using miR-1 and miR-126-5p and highlight the functional importance of these miRNAs in angiogenesis by targeting the BCL2 and PIK3R2 proteins.

Background: Asthma remains a critical global health concern impacting diverse age groups, with incidence rates rising continuously. Recent studies have identified elevated levels of kallikrein-related peptidase 13 (KLK13) in nasal lavage specimens of asthma patients; however, its functional mechanisms remain explored.

Methods: An experimental asthma model was established in mice through ovalbumin (OVA) sensitization with an Al(OH)₃ adjuvant. The role of KLK13 was evaluated using immunohistochemistry, hematoxylin-eosin, and Masson trichrome staining, pulmonary function testing, enzyme-linked immunosorbent serological assay (ELISA), biochemical measurements, and immunoblotting.

Results: OVA-challenged mice exhibited marked upregulation of KLK13 expression. Genetic silencing of KLK13 reduced airway hyperresponsiveness in the asthma model. Histological analysis showed that OVA exposure caused extensive peribronchial inflammatory cell infiltration, bronchial wall thickening with luminal narrowing, and pulmonary collagen accumulation, all of which were significantly improved by KLK13 knockdown. OVA administration also induced substantial increases in interleukin (IL)-4, IL-5, IL-13, and immunoglobulin E, while KLK13 silencing significantly attenuated these elevations. Biochemical assays revealed increased malonaldehyde content and reactive oxygen species generation, alongside decreased superoxide dismutase activity and glutathione peroxidase levels in OVA-exposed mice; these changes were effectively normalized by KLK13 knockdown. At the molecular level, KLK13 inhibition reduced phosphorylation of inhibitor of nuclear factor-κB (NF-κB) alpha and p65 subunits, thereby suppressing activation of NF-κB pathway in OVA-induced asthma.

Conclusion: KLK13 depletion ameliorates asthmatic pathology by reducing airway inflammation, preventing structural remodeling, and restoring redox balance, primarily through NF-κB signaling modulation.

Adenoid hypertrophy (AH) and combined adenotonsillar hypertrophy (ATH) are primary causes of childhood sleep-disordered breathing (SDB), and they are strongly correlated with atopic diseases affecting the respiratory mucosa. Allergen sensitization, class-switching of B cells, and IgE production in the adenotonsillar tissue, namely local atopy, are crucial steps in the pathogenesis of allergic rhinitis (AR) and asthma. The adenotonsillar tissue is also responsible for a considerable part in circulating specific IgE, potentially contributing to the pathogenesis of atopy in other organs. Atopic children experience fewer benefits from adenotonsillectomy compared to their nonatopic counterparts. However, this surgical intervention is effective in relieving both obstructive and allergic symptoms in children with concomitant ATH and AR or asthma. Adjunctive treatments such as allergen immunotherapy reduce the risk of recurrence in atopic children undergoing adenotonsillar surgery. This review focuses on the evidence linking local adenotonsillar IgE sensitization and the atopic march and its implications in the treatment and outcomes of both conditions.

Background: Bacillus licheniformis is a Gram-positive bacterium associated with foodborne illnesses and opportunistic infections in immunocompromised individuals, resulting in significant economic and health burdens. Despite its significance, no preventive or therapeutic vaccines currently exist against B. licheniformis.

Objective: This study aimed to design a multi-epitope vaccine construct against B. licheniformis using immunoinformatic and bioinformatic approaches, integrating the One Health perspective.

Materials and methods: Strains of B. licheniformis were isolated from soil and food samples and identified through 16S rRNA gene amplification and sequence analysis. Two antigenic proteins, WP_075876128.1 (hypothetical protein) and WP_009328059.1 (MATE family efflux transporter), were selected as vaccine targets based on antigenicity scores of 0.582 and 0.835, respectively. Immunoinformatics tools were used for epitope prediction, vaccine construct assembly, structural modeling, and immune simulations. Molecular docking was used to assess vaccine-receptor interactions with Toll-like receptors (TLRs) 1, 2, and 5.

Results: The designed vaccine construct exhibited favorable physicochemical properties, including structural stability, thermostability, solubility, and hydrophilicity. Immune simulation predicted a strong immune response, characterized by approximately 225 B-memory cells per mm³ and around 8,500 combined IgM and IgG counts. Docking studies revealed the stable binding of the vaccine construct to TLR1, TLR2, and TLR5, supported by favorable binding free energy values, indicating a robust immunogenic potential.

Conclusion: The immunoinformatically designed multi-epitope vaccine candidate demonstrated high antigenicity, stability, and strong immune-stimulatory capacity against B. licheniformis. These findings support its potential for further in vitro and in vivo validation. This study highlights the effectiveness of immunoinformatic tools in rational vaccine design and reinforces the One Health approach, which links human, animal, and environmental health.

Leishmaniasis is an endemic disease in many countries that affects vulnerable populations of humans, dogs, and cats. This study employs immunoinformatics to design a multi-epitope vaccine construct for leishmaniasis by identifying vaccine targets on the protein Pteridine Reductase. T-cell and B-cell epitopes were screened for antigenicity, toxicity, and allergenicity. Shortlisted T-cell targets were confirmed to have appropriate IC values (≤ 50 nM and ≤ 500 nM for MHC I and MHC II, respectively). One B-cell epitope, six MHC class I epitopes, and 25 MHC class II epitopes were selected for inclusion in the vaccine construct, which was linked with EAAAK, CPGPG, and AAY linkers, along with a CPG Oligodeoxynucleotide adjuvant. The vaccine construct had a Ramachandran score of 89.9% and an Errat score of 98.4615. HLA alleles were predicted to produce an immune response in 81.8% of the global population, indicating encouraging potential for broad immunogenicity. Successful binding of the vaccine construct with TLR-9 was confirmed through molecular docking, and the docked complex exhibited a low eigenvalue of 2.06e-0.6 and a ΔG of -11.8 kcal mol-1, indicating stable binding and a high level of flexibility. Codon optimization was carried out, followed by in-silico cloning of the vaccine in Escherichia coli K12 strain using the vector pET-21a (+). These results suggest that the vaccine is stable and capable of eliciting a promising immune response against Leishmania, making it a favorable candidate for experimental trials.

Mepolizumab is a monoclonal antibody targeting interleukin-5 that has been approved for the treatment of severe eosinophilic asthma (SEA) and chronic rhinosinusitis with nasal polyps (CRSwNP). This study aims to evaluate the sinonasal outcomes and safety of mepolizumab in patients with CRSwNP and SEA. This retrospective, real-life study included 19 patients aged 18 years and older who received 100 mg of subcutaneous mepolizumab every 4 weeks for at least 12 months. Sinonasal symptom severity, rhinorrhea, nasal congestion/obstruction, postnasal drip, and loss of smell were assessed using the visual analog scale (VAS). Disease-specific quality of life was assessed using the sino-nasal outcome test-22 (SNOT-22). The history of endoscopic sinus surgery (ESS) was evaluated for each patient. Asthma-related outcomes included the asthma control test (ACT), number of exacerbations, and daily systemic corticosteroid dose. Evaluations were conducted at baseline, 6 months (t6), and 12 months (t12). Adverse events were also recorded. The median age was 49 years (min-max: 29-63), and 57.9% of patients were female. Compared with baseline, significant improvements were observed in all VAS parameters and total/subdomain SNOT-22 scores at both t6 and t12. The number of asthma exacerbations and systemic corticosteroid doses decreased significantly. No patient required ESS during the follow-up period. Only two patients experienced mild injection-related side effects. Mepolizumab treatment has resulted in significant improvement in sinonasal symptoms and quality of life. These findings support the use of mepolizumab as a safe and effective option in selected patients with CRSwNP and concomitant SEA.