Asian Pacific journal of allergy and immunology最新文献

Background: Interleukin (IL)-5 is essential for allergen induced eosinophilic airway inflammation, but not activation of T helper type 2 (Th2) cells in the lung. Although an excessive Th2 reaction is observed without IL-5 signaling, the mechanisms have remained unknown.

Objective: To evaluate the negative-feedback mechanism in eosinophilic airway inflammation, we examined IL-33 triggered eosinophilic airway inflammation in IL-5Rα-/- mice.

Methods: Mice were administered intranasal IL-33 for 3 days. Airway hyperresponsiveness (AHR) was evaluated and bronchoalveolar lavage (BAL) was performed 24 h after the last IL-33 treatment. The number of inflammatory cells and cytokine levels in the BAL fluid (BALF) were analyzed, and histologic examination was performed.

Results: Compared with IL-33 treated wild-type (WT) mice, intranasal administration of IL-33 in IL-5Rα-/- mice reduced eosinophilic airway inflammation, AHR, and basement membrane thickening, while we found excessive IL-33 induced IL-5 and IL-13 production in the airway without IL-5 signaling. The numbers of eosinophils with a ringshaped nucleus (resident) and segmented nucleus (inflammatory) were increased in WT mice, but not in IL-5Rα-/- mice following intranasal administration of IL-33, and the numbers of SiglecF-positive eosinophils with (resident) or without (inflammatory) expression of CD62L were also significantly increased by IL-33 treatment in WT mice, but not in IL5Rα-/- mice. The number of ILC2 cells in the BALF was significantly higher in IL-33 treated IL-5Rα-/- mice than in IL-33 treated WT mice.

Conclusions: These findings suggest the possibility that IL-5 induced eosinophils contribute to the negative-feedback mechanisms in IL-33 induced ILC2 mediated airway inflammation.

Asthma is a chronic inflammatory airway disease characterized by variable respiratory symptoms and reversible airflow limitation. Despite significant advances in pharmacologic and immunotherapeutic treatment, definitive remission or cure remains elusive. Asthma remission is defined as a sustained absence of symptoms, exacerbations, and lung function decline, with or without ongoing therapy. In contrast, an asthma cure implies permanent disease eradication marked by lifelong symptom resolution, no need for maintenance or rescue medication, preserved lung function, and absence of airway inflammation. To date, no intervention has been proven to cure asthma. Consequently, clinical remission has emerged as a more achievable and meaningful goal in asthma management. This review summarizes recent findings on remission rates, key factors influencing asthma remission, and the impact of various therapeutic strategies-including immunotherapy and advanced biologics. We also highlight evidence underscoring the foundational role of comprehensive asthma care. Asthma should be managed within the context of a unified allergic airway disease; thus, systematic identification and treatment of coexisting conditions such as allergic rhinitis and rhinosinusitis, nasal polyps is essential, as they often exacerbate lower airway symptoms. Routine nasal irrigation, environmental control measures, and attention to modifiable lifestyle factors-such as sleep hygiene, physical activity, and weight management-are critical. When consistently implemented, these holistic approaches may significantly improve disease control and support the achievement of clinical remission. Achieving a cure for asthma remains the ultimate goal, necessitating a long-term commitment and strategically designed basic and clinical research to determine its viability.

Background: Nasal steroids are commonly prescribed to reduce nasal side effects, which are the primary cause of continuous positive airway pressure (CPAP) intolerance in obstructive sleep apnea (OSA) patients.

Objective: We conducted a systematic review and meta-analysis of OSA patients to assess the effect of nasal steroids on CPAP compliance and nasal symptoms.

Methods: PubMed, Scopus, Ovid, and Cochrane Library were searched through March 2022. Randomized controlled trials (RCTs) evaluating the effects of nasal steroids on CPAP compliance in adult patients, which reported quantitative data on CPAP use and nasal symptoms, were included.

Results: Three RCTs (224 patients) were eligible for the meta-analysis. At the 4-week follow-up, the study did not demonstrate a statistically significant difference in CPAP compliance (average hours of CPAP use per night: mean difference 0.45; 95% confident interval (CI) (-0.01, 0.90); P = 0.06, percentage of nights device used: mean difference 1.79; 95%CI (-2.59, 6.17); P = 0.42). There was also no difference in overall nasal symptoms (mean difference 0.47, 95%CI (-0.00, 0.94); P = 0.05), with significantly more sneezing and rhinorrhea among patients with nasal steroids (sneezing: mean difference 0.64, 95%CI (0.23, 1.05); P = 0.002, rhinorrhea: mean difference 0.78, 95%CI (0.24, 1.31); P = 0.005).

Conclusions: At the 4-week follow-up, the pooled results did not demonstrate significant benefits of nasal steroids on CPAP compliance. There was also no significant benefit for relieving nasal symptoms. To further explore the benefit of nasal steroids on CPAP use, additional, longer-term studies are required.

Background: House dust mites (HDM) are a major source of allergens, and more than 30 HDM allergens have been identified to date. Recently, Der p 23 was reported to be a major allergen that is related to the severity of allergic responses.

Objective: This study aimed to characterize IgE-sensitization and cross-reactivity between Der f 23 and Der p 23 in Korean patients with allergy.

Methods: We produced recombinant Der f 23 and Der p 23 using a yeast Pichia expression system. The IgE binding activity of Der f 23 and Der p 23 was evaluated by enzyme-linked immunosorbent assay (ELISA) using sera from 194 Korean HDM-sensitized patients. The cross-reactivity between Der f 23 and Der p 23 was then assayed using competitive ELISA.

Results: Among the 194 HDM-allergic patients, IgE reactivity to rDer f 23 and rDer p 23 was observed in 45.36% (88/194) and 43.81% (85/194) of the samples, respectively. Competitive ELISA with pooled serum from 10 patients revealed that rDer p 23 inhibited 86.1% of the rDer f 23 IgE reactivity and rDer f 23 inhibited 61.1% of the rDer p 23 IgE reactivity.

Conclusions: Group 23 HDM allergens, Der f 23 and Der p 23, show moderate sensitization, with 45.36% and 43.81% of Korean patients with allergy reacting to them, respectively. Significant IgE cross-reactivity was observed between the two allergens. These findings can facilitate the development of component-resolved diagnosis and allergen-specific immunotherapy in the future.

Background: The global COVID-19 pandemic, caused by SARS-CoV-2, has highlighted the importance of understanding immune responses elicited by vaccines.

Objective: This study evaluated antibody and T cell responses to the inactivated CoronaVac vaccine, as well as the role of pre-existing immunity to common human coronaviruses (HCoVs) in shaping vaccine-induced immunity.

Methods: We enrolled 64 participants (17 males and 47 females) and measured IgG levels against HCoVs before and after vaccination. T cell responses were analysed by stimulating peripheral blood mononuclear cells (PBMCs) with wild-type, Delta, and Omicron spike peptides.

Results: We found pre-existing antibodies against HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43 were present before vaccination. Notably, a positive correlation was observed between pre-existing antibodies to HCoV-229E and HCoV-HKU1 and anti-RBD IgG levels post-vaccination. Pre-existing CD4+ T cell responses were observed for the wild-type strain before vaccination, with a significant reduction in IFN-γ secretion after Delta re-stimulation and partial restoration after Omicron re-stimulation. IL-4 production by CD4+ T cells was significantly reduced upon re-stimulation with Delta and Omicron compared to wild-type. CD8+ T cells again showed a reduction of IL-4 production after Delta re-stimulation compared to the original strain.

Conclusions: This work demonstrate that CoronaVac induces robust humoral and cellular immune responses, though variant-specific responses vary. Pre-existing immunity to certain HCoVs may influence vaccine-induced antibody responses, underscoring the importance of monitoring immunity to emerging SARS-CoV-2 variants and informing future vaccine design.

Background: Denatonium benzoate (DB), one of the most bitter compounds known to man, is used for alcohol denaturation. Some reports have demonstrated that asthmatic symptoms are associated with DB exposure, but the possible links between DB and immunoglobulin E (IgE)-mediated allergy susceptibility have not yet been examined.

Objective: This study investigated the effects of DB on in vitro IgE-mediated mast cell degranulation and food allergy in BALB/c mice.

Methods: IgE-sensitized rat RBL-2H3 cells (a basophilic leukemia mast cell line) and human KU812 cells (a basophilic cell line) and mice with ovalbumin (OVA)-induced allergy were treated with DB. Histamine release, calcium ion (Ca²⁺) influx, phosphorylated spleen tyrosine kinase (p-Lyn) and phosphorylated phospholipase C-γ (p-PLCγ) levels, OVA-specific IgE, anaphylactic symptoms, and the cell-surface expression of the high-affinity IgE receptor α-subunit (FcεRIα) on mast cells were evaluated.

Results: DB increased histamine release, Ca²⁺ mobilization, and p-Lyn and p-PLCγ levels in IgE-mediated activated RBL-2H3 and KU812 cells, and enhanced the cell-surface expression of FcεRIα messenger RNA (mRNA). In mice, DB increased the severity of OVA-induced anaphylactic and diarrheic symptoms, the mucus thickness in the jejunum, histamine and OVA-specific IgE levels, and FcεRIα mRNA in isolated mucosal mast cells.

Conclusions: Our work indicates that DB promotes IgE-mediated mast cell degranulation and OVA-induced allergic diarrhea in BALB/c mice, providing evidence that exposure to DB promotes allergy susceptibility.

Background: The role of anti-elastin antibody (Ab) in the lung is unclear, although they may be involved in chronic obstructive pulmonary disease (COPD). Recently, increased anti-elastin Ab levels were reported in asthma.

Objective: To elucidate the role of anti-elastin Ab in asthma, we created a murine asthma model. Anti-elastin Ab in the airway was neutralized by intratracheal administration of elastin peptide, and the inhibitory effects of anti-elastin Ab on airway remodeling were evaluated.

Methods: BALB/c mice were immunized with ovalbumin (OVA) on days 0 and 14. After immunization, the mice received booster OVA via inhalation twice per week for 9 weeks, and bronchoalveolar lavage fluid (BALF) and lung tissues were evaluated.

Results: In lung tissues, airway remodeling occurred after 9 weeks of OVA sensitization. Peak levels of anti-elastin Ab and eosinophils in BALF were detected after 3 weeks of OVA sensitization. Anti-elastin Ab and eosinophil levels in BALF were significantly reduced after 3 weeks by the neutralization of anti-elastin Ab. Peak transforming growth factor-β1 levels in BALF were detected at 3 weeks after OVA sensitization and were significantly reduced by the neutralization of anti-elastin Ab. Airway remodeling in lung tissues was also significantly inhibited by the neutralization of anti-elastin Ab.

Conclusions: In our murine asthma model, anti-elastin Ab was recruited to the airway by OVA-induced allergic inflammation. Airway remodeling was inhibited by the neutralization of anti-elastin Ab. Anti-elastin Ab may contribute to the progression of airway remodeling.

Background: Wheat allergy is one of the most prevalent allergens in Korea, decreasing quality of life and causing nutritional repercussions.

Objective: We aimed to investigate the efficacy and safety of the home-based wheat oral immunotherapy (OIT) using wheat noodles in children with a wheat allergy.

Methods: We conducted a retrospective study involving 72 children aged 3 to 17 years diagnosed with a wheat allergy. Patients received wheat OIT using wheat noodles (n = 50) and were compared with a historical control group (n = 22). Baseline characteristics, adverse events, and immunological changes were assessed. Predictors of successful desensitization were identified using logistic regression analysis.

Results: Among 50 patients completing the up-dosing phase, 82.0% achieved desensitization to 2,400 mg of wheat protein, compared to 4.5% in the control group (p < 0.001). During the up-dosing period, the median number of adverse reactions per person was 2, and anaphylaxis occurred in 30.0% (15/50). However, there were no life-threatening adverse events. In multivariable analysis, the presence of asthma (adjusted odds ratio [aOR], 8.88; 95% confidence interval [CI], 1.10-71.97; p = 0.041) and a higher ratio of specific IgE (sIgE) to ω-5-gliadin and total IgE (aOR 19.09, 95%CI 1.21-300.80, p = 0.036) were significantly associated with treatment outcomes of wheat OIT.

Conclusion: Our study showed the safety and efficacy of home-based wheat OIT using boiled noodles in Korean children with wheat allergies. Careful consideration is warranted for patients with elevated baseline sIgE to ω-5-gliadin to total IgE ratio and a history of asthma.

Background: Fire ant, honey bee, and wasp allergen extracts are useful in the diagnosis and treatment of severe Hymenoptera allergic patients.

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: SPT and ID with local or commercial insect venoms could help in confirming and/or identifying the causative insects.

Background: Renal tubulointerstitial fibrosis is known to occur as a result of epithelial cell transformation into myofibroblasts via the epithelial-to-mesenchymal transition (EMT) process. It has been reported that macrophages, regulatory T (Treg) cells, and gamma delta T (γδ T) cells can promote fibrosis via EMT in vivo.

Objective: Our study intended to detect whether thymocytes can induce renal tubular cells to undergo the EMT.

Methods: Rat thymocytes were activated by phytohemagglutinin and concanavalin A. The rat renal tubular epithelial cells (NRK-52E) were incubated in a conditioned medium harvested from activated thymocytes or co-cultured with freshly isolated thymocytes for 48 hours. Real-time reverse transcription-polymerase chain reaction, immunofluorescence, and western blotting analysis were used to test the expression of the epithelial and mesenchymal markers in NRK-52E cells. Scratch assay was designed to test the cell migration abilities of NRK-52E cells. Student's t test and oneway analysis of variance test were used for statistical analysis.

Results: The combined stimulation with phytohemagglutinin and concanavalin A activated the primary isolated rat thymocytes. After treatment with conditioned medium or freshly isolated thymocytes, the expression levels of cytokeratin 19 and E-cadherin were downregulated in NRK-52E cells, while the mRNA and protein expression levels of alpha-smooth muscle actin, desmin, and vimentin were upregulated (P < 0.05). We found that the cell migration abilities of the induced NRK-52E cells were significantly improved.

Conclusions: Both activated rat thymocytes (more percentage of CD8+ T cells) and freshly isolated thymocytes have promoting effects on the EMT of NRK-52E cells.