Allergic asthma in children significantly impacts quality of life, and immunotherapy, including subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), has emerged as an effective treatment. However, their comparative immunological mechanisms remain unclear. This study aimed to compare the effects of SCIT and SLIT on immune response in children with allergic asthma and to explore their underlying immunological mechanisms. A total of 86 children aged 5-12 years with allergic asthma who visited Hangzhou Children's Hospital were prospectively enrolled and randomly assigned to three groups: inhaled corticosteroids (ICS) group (n = 30), SCIT group (n = 30), and SLIT group (n = 26). Clinical and immunological parameters-including Childhood Asthma Control Test (C-ACT) scores, forced expiratory volume in the first second percentage (FEV1%), Th17, Treg cells, and serum levels of IL-17, IL-9, IL-10-were assessed before treatment and after one year. After treatment, all three groups showed significant improvements in C-ACT scores and FEV1% compared to baseline (all p < 0.05). The SCIT and SLIT groups demonstrated greater improvements than the ICS group (all p < 0.05), with no significant differences between the SCIT and SLIT groups (p > 0.05). In terms of immune markers, significant differences were observed in all parameters before and after treatment in the SCIT and SLIT groups (all p < 0.05), while Treg levels in the ICS group remained unchanged (p > 0.05). No statistically significant differences in immune markers were found among the three groups post-treatment (all p >0.05). Both SCIT and SLIT, when combined with ICS, offer superior efficacy compared to ICS monotherapy. The comparable immunological changes observed in SCIT and SLIT suggest a shared mechanism of immune tolerance, potentially mediated through Treg cell induction.

Asthma is a heterogeneous disease with diverse and poorly defined phenotypes, especially in children. We aimed to classify childhood asthma phenotypes using unsupervised cluster analysis based on type 2 (T2) biomarkers and to evaluate their clinical characteristics and outcomes. We retrospectively analyzed 614 pediatric patients. Hierarchical clustering was performed using four variables: age, absolute eosinophil count (AEC), eosinophil cationic protein (ECP), and total immunoglobulin E (IgE). Clinical characteristics and two-year clinical outcomes were compared across clusters. The effect of age was examined using Analysis of Covariance (ANCOVA) and age-tertile subgroup analyses. Three distinct clusters were identified. Cluster 2, the T2-high asthma group (n = 157; median age: 8.0 years), was characterized by male predominance (69.4%), the highest levels of T2 biomarkers (AEC, ECP, IgE, FeNO; all P < 0.001), airway hyperresponsiveness (BDR, P = 0.024; PC20, P < 0.001), and reduced lung function (FEV1, P = 0.002). In contrast, Cluster 1 (n = 252; median age: 4.0 years) showed the highest exacerbation and steroid use rates but relatively low T2 biomarker levels. Cluster 3 (n = 205; median age: 12.0 years) had moderate T2 levels and the lowest exacerbation burden. After adjusting for age, Cluster 2 maintained 4-6 folds higher T2 biomarker levels compared to other clusters (all P <0.001). These cluster-specific differences were not observed in the age tertile subgroup analysis. The identified school-age T2-high cluster in childhood asthma exhibits distinct immunological and clinical phenotypes, characterized by high airway hyperresponsiveness, atopic features, and decreased lung function.

Toll-like receptor 9 (TLR9), located in the endosomal compartment, is known to play a role in inflammation by recognizing oligonucleotides that contain CpG motive (CpG-ODN). Signaling by TLR9 leads to the production of proinflammatory cytokines and can trigger cell death. This study aims to investigate the molecular mechanism of pyroptosis induced by ODN1826 in the mouse macrophage cell line (Raw264.7). The protein expression and the amount of lactate dehydrogenase (LDH) of ODN1826-treated cells were determined by immunoblotting and LDH assay, respectively. In addition, the level of cytokine production was observed by ELISA assay and the ROS production was determined by flow cytometry. Our results showed that ODN1826 induced pyroptosis as judged by LDH releases. Furthermore, caspase-11 and gasdermin D activation, which are the key molecules in pyroptosis, were also observed in ODN1826-activated cells. Moreover, we also demonstrated that Reactive Oxygen Species (ROS) production by ODN1826 is essential for caspase-11 activation and gasdermin D release, which leads to pyroptosis. ODN1826 induces pyroptosis in Raw264.7 cells via caspase-11 and GSDMD activation. Moreover, the production of ROS by this ligand plays an essential role in the regulation of caspase-11 and GSDMD activation, which then controls pyroptosis in TLR9 activation.

Hypersensitivity reaction to vaccines has been reported to occur in 5 per 100,000 doses. Although hypersensitivity reactions can occur to either the active vaccine component or other components such as excipients, outcome data from skin testing and provocation remains limited. To evaluate the role of skin testing and vaccine provocation in patients with an allergy label to vaccine. This is a single centre, prospective study between March 2021 and November 2021 of adults with known allergy to non-COVID vaccine. All participants underwent skin prick testing (SPT) and intradermal testing (IDT) to vaccine and excipients. A subset of patients with negative skin testing underwent graded vaccine provocation. A total of 264 adults were evaluated. The most common index vaccine reactions were nonspecific rash (47.7%), angioedema (32.2%) and itch (25.0%). All patients had negative SPT to vaccines and excipients. Thirty patients (11.4%) had positive IDT to Hepatitis A, Hepatitis B, Human Papilloma Virus (HPV), Influenza, Measles-Mumps-Rubella (MMR), Pneumococcal, Rabies, Diphteria, Tetanus and Pertussis (DTaP). Out of 234 patients with negative IDT, 32 patients (12.1%) underwent vaccine provocation. Three patients (9.4%) developed reaction to influenza and MMR vaccine. One patient required systemic corticosteroids, one required antihistamine, and another patient did not require any treatment. None required admission or attendance at emergency department. The majority of allergy labels to vaccine are inaccurate based on low skin test positivity and low reaction rates on vaccine provocation. Vaccine provocation is safe. Excipients are unlikely to be the main cause of hypersensitivity reactions in vaccines.

Fire ant, honey bee, and wasp allergen extracts are useful in the diagnosis and treatment of severe Hymenoptera allergic patients. To evaluate the result of skin prick test (SPT) and intradermal test (ID) compared between local and commercial insect allergen extracts in patients with severe Hymenoptera sting allergy. SPT and ID using local and commercial insect allergen extracts were performed. Specific IgE (sIgE) to honey bee, wasp, and fire ant; component-resolved diagnosis (CRD); (rApi m1, rApi m2, rApi m3, rApi m5, rApi m10, rVes v5, rPol d5, and rVes v1); and, cross-reactive carbohydrate determinant (CCD) were performed. Twenty-seven patients were included. Twenty-five had anaphylaxis, and 2 had severe systemic skin reaction. Positive skin test (SPT and/or ID) result from local and commercial allergen extracts was 74% vs. 67% for fire ant, 48% vs. 59% for honey bee, and 52% vs. 74% for yellowjacket. Local and commercial allergen extracts showed substantial agreement for fire ant (k = 0.647, p = 0.001) and honey bee (k = 0.632, p = 0.001), and moderate agreement for wasp (k = 0.547, p = 0.001). When compared with sIgE subtracted with CCD and/or CRD, skin test results of local fire ant allergen extract showed higher sensitivity (87% vs. 67%), specificity (42% vs. 33%), and accuracy (67% vs. 52%) than commercial extract. Commercial honey bee and wasp showed higher sensitivity (62% vs. 50%, 85% vs. 65%) and accuracy (63% vs. 52%, 78% vs. 70%), respectively. SPT and ID with local or commercial insect venoms could help in confirming and/or identifying the causative insects.

Bee venom (BV) hypersensitivity can be severe and potentially life-threatening. Beekeepers heavily exposed to bee stings and are thus at a high-risk group. The data on bee sting reactions among beekeepers in Thailand is limited. To determine the prevalence, clinical and immunological characteristics, and the knowledge of BV hypersensitivity in Thai beekeepers. A self-reported questionnaire survey about BV reactions in beekeepers were conducted. Further blood test for immunological parameters: serum BV-specific IgE (BV sIgE), phospholipase A2-specific IgE (Api m1 sIgE), and BV-specific IgG4 (BV sIgG4) were compared between non-allergic beekeepers, patients with a history of bee sting anaphylaxis and the non-allergic control group. A total of 202 out of 447 questionnaires (response rate 45%) were returned. The median age was 46.7 years. Systemic reactions were documented in 6.4%. Younger than 45 years was found to be a factor associated with systemic reactions (OR, 4.35; 95% CI, 1.16-16.31). The BV sIgE and Api m1 sIgE were significantly higher in the anaphylaxis group (p = 0.001). The median of BV sIgG4 was significantly higher in non-allergic beekeepers (p = 0.001). For the knowledge of BV hypersensitivity, 56.4% recognized that BV hypersensitivity could be fatal but only 6% knew about epinephrine auto-injector device. The prevalence of systemic reactions after stings among Thai beekeepers was not high, which might be due to the tolerance induced by natural exposure via sIgG4. The level of knowledge of BV hypersensitivity among beekeepers was insufficient, more education must be provided.

Delayed pressure urticaria (DPU) is a chronic inducible subtype of urticaria, characterized by painful erythematous swelling triggered by sustained mechanical pressure. After pressure stimuli, lesions often appear within 4 to 6 hours, peak around 6 hours later, and persist for 8 hours to 3 days. More than half of patients may have associated symptoms, most often malaise and fatigue. The diagnosis of DPU is based on clinical history and confirmation through provocation testing. Dermographic tester and weighted rod testing are recommended as diagnostic tools by several current guidelines due to their reproducibility and capability to determine individual trigger thresholds. Although the exact pathogenesis remains unclear, mast cell activation, histamine release, eosinophil infiltration, and multiple mediators have been implicated. These mechanisms likely interact synergistically, contributing to the clinical manifestations of DPU. This article reviews the pathogenesis, histopathological findings, effector cells, inflammatory mediators, neuropeptides, adhesion molecules, and unmet clinical needs associated with DPU. A deeper understanding of these complex processes may facilitate the development of more effective targeted immunomodulators and biological therapies for severe and treatment-resistant cases of DPU.

Ambrosia (ragweed) pollen is a major allergenic source, but Ambrosia trifida allergens remain understudied. Triosephosphate isomerase, a conserved pan-allergen in plants, has not been reported in weed pollen. To identify and characterize the novel allergen (Amb t 18) and evaluated its clinical relevance. Amb t 18 cDNA was cloned and expressed in E. coli. Natural (nAmb t 18) and recombinant (rAmb t 18) proteins were purified for structural analyses (CD spectra) and IgE-reactivity testing (ELISA/basophil activation). Cross-reactivity with homologs Pla a 7 and Tri a 31 was assessed through inhibition ELISA. Structural analyses included 3D modeling, sequence alignment, and phylogenetics. Natural and recombinant Amb t 18 exhibited similar CD spectra. Amb t 18 reacted with 35.1% (13/37) of serum samples, inhibited 17.56% of IgE-binding to pollen extracts, and activated basophils. In some sera, its IgE-binding activity exceeded that of ragweed pollen extracts. It shared 82% sequence identity with Pla a 7 and Tri a 31, grouped together in the phylogenetic tree. The recombinant Amb t 18 reacted with Pla a 7 or Tri a 31 IgE-positive sera from Platanus acerifolia or Triticum aestivum-allergic patients, rAmb t 18, rPla a 7, and rTri a 31 inhibited IgE binding to rAmb t 18 by 76.70%, 5.80%, and 21.94%, respectively. Amb t 18 was identified as a novel Ambrosia trifida pollen allergen, the first of its type in ragweed pollen. These findings may aid in developing new diagnostic and therapeutic approaches for ragweed allergy.

Nowadays, moisturizers contain non-steroidal anti-inflammatory agents that help for treatment of atopic dermatitis (AD). Defensil® (black currant seed oil, sunflower oil, and balloon vine), a new anti-inflammatory, obtained from plant extracts, remain had a few studies for AD. To compare the effectiveness of moisturizer containing 3% Defensil®, 5% dexpanthenol and ceramide (LDC) with 5% urea cream in childhood AD treatment. Thirty-eight patients with diagnosis of atopic dermatitis by UK working party's criteria were recruited in randomized, controlled, double-blinded 4-week study. The patients were received with twice-daily application of LDC cream on one side of the body and 5% urea cream on the opposite side. The clinical severity was assessed by modified scoring of atopic dermatitis (SCORAD). Median time to remission was analyzed by survival analysis. Thirty-seven out of 38 patients accomplished the protocol. The clinical SCORAD significantly improved from baseline in both groups (p < 0.001) after 2 and 4 weeks. Furthermore, the LDC group significantly reduced severity of disease better than the 5% urea group (P = 0.043). The mean difference SCORAD scores were -13.83 (±1.83) and -13.04 (±3.22) respectively. Stratum corneum hydration (SCH) was enhanced from baseline in both groups (p < 0.001) but no statistically significant difference between both groups. Median time to remission had no statistically significant difference (P = 0.697). The effectiveness of LDC cream is better than 5% urea cream for improving clinical atopic dermatitis. It was suggested that moisturizer containing LDC could be used for the treatment of mild-to-moderate childhood atopic dermatitis.