International Archives of Allergy and Immunology最新文献

{"title":"miR-337-5p Targets WNK1 to Promote IL-13-Induced Nasal Epithelial Inflammation in Allergic Rhinitis.","authors":"Shuang Wu, Ye Xu, Jian Qiao","doi":"10.1159/000553284","DOIUrl":"10.1159/000553284","url":null,"abstract":"<p><strong>Introduction: </strong>Allergic rhinitis (AR) represents a prevalent chronic inflammatory disease affecting the nasal mucosa, yet effective diagnostic biomarkers and therapeutic targets remain elusive. This investigation sought to examine plasma miR-337-5p expression and its diagnostic utility in AR patients, additionally dissecting its role and molecular mechanism during IL-13-induced nasal epithelial inflammatory injury.</p><p><strong>Methods: </strong>RT-qPCR quantified plasma miR-337-5p in 100 AR patients versus 100 controls, with ROC curve analysis establishing diagnostic value. For in vitro experiments, IL-13 exposure generated a Th2-type inflammation model in HNEpC cells. Cells transfected with miR-337-5p mimic or inhibitor were subjected to assessments of cell viability, apoptosis, inflammatory cytokines (IL-6, IL-8), plus oxidative stress markers (SOD, MDA). Bioinformatics predicted target genes, subsequently validated through dual-luciferase reporter assay. Rescue experiments further clarified WNK1 involvement.</p><p><strong>Results: </strong>AR patients exhibited significantly higher plasma miR-337-5p concentrations, which correlated positively with TNSS scores and eosinophil (EOS) counts. The resulting ROC curve demonstrated an AUC of 0.840, reflecting good diagnostic value. Within IL-13-stimulated HNEpC cells, miR-337-5p overexpression worsened cell injury, apoptosis, inflammatory cytokine release, and oxidative stress, while miR-337-5p inhibition conferred protection. Bioinformatics, coupled with dual-luciferase reporter assay, identified WNK1 as a direct miR-337-5p target. WNK1 expression was reduced in AR patients and showed a negative correlation with miR-337-5p levels. WNK1 knockdown partially abrogated the protective impact of miR-337-5p inhibition.</p><p><strong>Conclusions: </strong>Increased plasma miR-337-5p holds potential as a diagnostic biomarker for AR. Through WNK1 targeting, miR-337-5p aggravates IL-13-induced nasal epithelial inflammatory injury, implicating its contribution to AR pathogenesis.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1-9"},"PeriodicalIF":2.3,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Laboratory Characteristics of Fruit and Vegetable Allergy in Childhood: A Five-Year Retrospective Evaluation.","authors":"Aslı Berivan Topçak, Merve Karaca Şahin, Nilay Çalışkan, Güler Yıldırım, Hamit Bologur, Hilal Güngör, Muhammed Fatih Erbay, Hasan Tunç Şarman, Çağla Öztürk Turan, Ömer Yılmaz Ulutaş, Şule Papağan, Sefika Ilknur Kökcü Karadag, Deniz Ozceker","doi":"10.1159/iaa/adfag005","DOIUrl":"10.1159/iaa/adfag005","url":null,"abstract":"<p><strong>Introduction: </strong>Fruit and vegetable allergies in childhood present with heterogeneous clinical features and are often influenced by cross-reactivity with aeroallergens. Despite their growing clinical importance, data on diagnostic accuracy and clinical phenotypes remain limited, particularly in regions where component-resolved diagnostic tests are not available.</p><p><strong>Methods: </strong>This 5-year retrospective cohort study evaluated children aged 0-18 years who presented to a tertiary pediatric allergy clinic between 2020 and 2025 with suspected fruit or vegetable allergy. Clinical history, skin prick test (SPT), specific IgE (sIgE), prick-by-prick test results, aeroallergen sensitization profiles, laboratory parameters, and oral food challenge (OFC) outcomes were reviewed. Only patients whose diagnoses were confirmed by OFC were included in the study.</p><p><strong>Results: </strong>A total of 19 OFC-confirmed cases were included. The median age at symptom onset was 41.5 months. Based on the total number of triggering foods (n = 23), the most common allergens were kiwi (17.4%) and strawberry (17.4%), while urticaria was the most frequent clinical manifestation at initial presentation (52.2%). Reaction types did not significantly differ across different allergen subgroups; however, patients with oral allergy syndrome had a significantly higher age of symptom onset (p = 0.002). Sensitization tests demonstrated limited diagnostic performance for predicting OFC-confirmed fruit and vegetable allergy, with a sensitivity of 47.4%, a specificity of 80.0%, a positive predictive value of 52.9%, a negative predictive value of 76.2%, and an overall diagnostic accuracy of 69.5%.</p><p><strong>Conclusions: </strong>Fruit and vegetable allergies in childhood are generally mild but may exhibit considerable clinical variability. Skin prick test and serum-specific IgE tests alone are insufficient for diagnosis, and OFC remains the gold standard for diagnostic confirmation. Larger, multi-center studies are needed to better characterize sensitization patterns and to establish reliable diagnostic cut-off values.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1"},"PeriodicalIF":2.3,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Not Everything Is Allergic: Skin Sometimes Tells a Different Story at the Immunology and Allergy Clinics.","authors":"Alper Ekinci, Zeynep Celebi Sozener, Handan Merve Erol Mart, Zeynep Keskin, Ayse Boyvat, Omur Aydin, Dilsad Mungan, Sevim Bavbek","doi":"10.1159/iaa/adfag003","DOIUrl":"10.1159/iaa/adfag003","url":null,"abstract":"<p><strong>Introduction: </strong>Patients frequently present to allergy and immunology clinics with cutaneous complaints attributed to self-perceived allergic conditions; however, many have non-allergic dermatologic diseases. We aimed to evaluate the demographic and clinical characteristics of non-allergic patients with dermatologic complaints.</p><p><strong>Methods: </strong>In this prospective study, patients presenting between June 1 and December 31, 2025, who received a non-allergic dermatologic diagnosis were included. Initial assessments were conducted in the immunology and allergy clinic, with dermatology consultation when needed. Demographic data, symptom characteristics and duration, prior dermatology visits, and final diagnoses were recorded.</p><p><strong>Results: </strong>A total of 218 patients were included. Median age was 45 years; 68.3% were female. Median symptom duration was 10.5 months, with 57.8% experiencing symptoms >3 months. Previous dermatology clinic applications were reported by 62.4%. Allergy beliefs included unspecified (49.5%), food-related (22.5%), drug-related (9.6%), and no suspicion (18.4%). The most frequent symptom was pruritus (83.9%). Common diagnoses included xerosis cutis (26.6%), insect bite reactions (10.6%), prurigo simplex (8.3%), seborrheic dermatitis (6.4%), acne vulgaris (6.0%), and rosacea (6.0%). Allergy-related beliefs were not significantly associated with age, sex, education, or symptom duration. Longer symptom duration was associated with a higher likelihood of previous dermatology visits (p<0.001).</p><p><strong>Conclusion: </strong>Non-allergic dermatologic conditions are common among patients with self-perceived allergic dermatologic conditions presenting to immunology and allergy clinics. Improved triage, interdisciplinary collaboration, and public education may reduce misinterpretation and unnecessary healthcare utilization.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1"},"PeriodicalIF":2.3,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics of chronic urticaria patients with and without systemic flares.","authors":"Ayşegül Pehlivanlar Ustaoğlu, Hazal Kayikçi, Çise Tüccar, Melek Cihanbeylerden, Gül Karakaya, Ali Fuat Kalyoncu, Ebru Damadoglu","doi":"10.1159/iaa/adfag001","DOIUrl":"10.1159/iaa/adfag001","url":null,"abstract":"<p><p>Intraduction: Chronic urticaria (CU) is not classified as a mast cell activation syndrome; however, some patients experience systemic flares fulfilling anaphylaxis criteria without identifiable triggers, posing diagnostic and therapeutic challenges. To characterize CU patients with systemic flares and identify factors associated with recurrent episodes.</p><p><strong>Methods: </strong>In this retrospective study at a tertiary allergy center, patients diagnosed with CU between 2015 and 2025 were screened. Among these, 192 had confirmed chronic urticaria based on disease duration and clinical evaluation. Patients with inducible urticaria subtypes associated with anaphylaxis and those with identifiable trigger-related reactions were excluded to avoid misclassification. The final cohort consisted of 70 patients, including 36 with systemic flares fulfilling clinical criteria for anaphylaxis and 34 without systemic flares.</p><p><strong>Results: </strong>A total of 70 patients (64.0% female; mean age 39.3±13.6 years) were included.Systemic flares occurred in 36 (51%) patients, most commonly presenting as moderate anaphylaxis (86.1%). Compared to group without systemic flares, blood basophil and lymphocyte counts were higher in the systemic-flare group. Higher lymphocyte counts were independently associated with systemic flares (OR = 3.35; 95%CI 1.31-8.56; p = 0.012), whereas baseline serum tryptase levels were not (OR = 0.77; 95%CI 0.57-1.04; p = 0.083). Patients with systemic flares were less likely to require escalation to second-line therapy with omalizumab for urticaria control (OR = 0.11; 95% CI 0.02-0.79; p = 0.028). Gastrointestinal involvement emerged as the sole independent predictor of recurrence (OR = 8.24; 95%CI 1.24-54.71; p = 0.029).</p><p><strong>Conclusion: </strong>This study identifies a subgroup of patients with CU who experience systemic flares fulfilling anaphylaxis criteria, and exhibit well-controlled urticaria with antihistamines, a lower need for omalizumab, and higher peripheral lymphocyte counts. Systemic flares with gastrointestinal symptoms was a risk factor for recurrent systemic flares in CU. Our findings suggest that a subset of patients with chronic urticaria may experience recurrent systemic flares accompanied by certain clinical differences and treatment patterns compared with conventional CU, although further prospective studies are needed to better characterize this group.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1"},"PeriodicalIF":2.3,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148602558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delayed-Type Drug-Induced Cutaneous Adverse Reactions in Children: Clinical Spectrum, Diagnostic Challenges, and Outcomes.","authors":"Selin Akyüz Oktay, Sule Haskologlu, Candan İslamoğlu, Gokcan Ozturk, Selin Sevinc, Tutku Baylan, Avniye Kubra Baskin, Hasret Erkmen, Nazli Deveci Demirbas, Tanil Kendirli, Aylin Heper, Figen Doğu, Aydan İkinciogullari","doi":"10.1159/iaa/adfag006","DOIUrl":"10.1159/iaa/adfag006","url":null,"abstract":"<p><strong>Introduction: </strong>Delayed-type cutaneous adverse drug reactions (CADRs) are T-cell-mediated hypersensitivity reactions that may present with variable clinical severity in children. They range from mild maculopapular exanthema (MPE) to severe, life-threatening mucocutaneous syndromes such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Data on pediatric delayed-type CADRs remain limited. They represent an important cause of morbidity in pediatric patients and require careful diagnostic evaluation. This study aimed to describe the clinical characteristics, etiologic agents, management strategies, and outcomes of pediatric patients with delayed-type CADR followed at a tertiary pediatric center.</p><p><strong>Methods: </strong>This retrospective case series included 33 pediatric patients diagnosed with delayed-type CADR between January 2013 and December 2024. Demographic features, suspected culprit drugs, clinical manifestations, laboratory and histopathologic findings, treatment approaches, and outcomes were reviewed. RegiSCAR, EuroSCAR, and SCORTEN criteria were applied for diagnostic classification and severity assessment of DRESS, AGEP, and SJS/TEN, respectively.</p><p><strong>Results: </strong>The median age was 9 years (range: 9 days-16 years); 17 patients were female. The most frequent diagnosis was MPE (n = 18, 54.5%), followed by DRESS (n = 5, 15.1%), SJS/TEN (n = 3, 9.1%), AGEP/ALEP (n = 3, 9.1%), erythema multiforme (n = 2, 6.0%), and symmetric drug-related intertriginous and flexural exanthem (n = 2, 6.0%). Antibiotics and antiepileptic drugs were the most commonly implicated drug classes. Systemic corticosteroids were administered in moderate-to-severe cases, and intravenous immunoglobulin was used in selected patients with DRESS and SJS/TEN. Four patients died due to underlying primary diseases; no CADR-related mortality was observed.</p><p><strong>Conclusion: </strong>This retrospective case series describes the heterogeneous clinical spectrum of delayed-type CADRs in children in a tertiary referral setting. In our cohort, MPE was the most frequent phenotype, while antibiotics and antiepileptic drugs were the most commonly implicated agents. A high burden of comorbidities, including immunosuppression and polypharmacy, was notable and may have influenced the observed clinical spectrum. Severe reactions required multidisciplinary management.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1"},"PeriodicalIF":2.3,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148602565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Incidence of Hereditary Angioedema: A Systematic Literature Review.","authors":"Timothy J Craig, Marc A Riedl, Tukisa D Smith, Ellen Kasireddy, Otto L T Lam, Monica R McClain","doi":"10.1159/000553023","DOIUrl":"10.1159/000553023","url":null,"abstract":"<p><strong>Introduction: </strong>Prior reports on the global prevalence of hereditary angioedema (HAE) have varied widely, and it remains uncertain as to what extent such variation can be attributed to regional differences. More accurate estimates of HAE prevalence can potentially raise awareness among clinicians and reduce diagnostic delay. This systematic literature review identified studies reporting on HAE prevalence, with the aim of generating pooled global/regional estimates.</p><p><strong>Methods: </strong>Relevant studies were identified through a systematic search of MEDLINE® and Embase (inception to June 21, 2024). Study selection, data extraction, and quality assessment were performed in duplicate by two independent reviewers; 5,225 studies were screened, with 41 publications (pertaining to 40 unique studies) being included.</p><p><strong>Results: </strong>Most studies were conducted in Europe (n = 22); other regions included Northern Eurasia (n = 1), North (n = 3) and South America (n = 1), Africa (n = 1), Middle East (n = 1), East Asia (n = 6), and Oceania (n = 1). Diagnostic methodology varied greatly, with a minority of studies citing an established guideline. Pooled diagnosed annual prevalence estimates (95% confidence interval) were 1.31 per 100,000 (0.83-2.08; type I HAE), 0.20 per 100,000 (0.14-0.29; type II HAE), 0.06 per 100,000 (0.01-0.40; HAE with normal C1-inhibitor [INH]), and 1.70 per 100,000 (1.58-1.83; combined types). Pooled estimates by region were 1.43 per 100,000 (0.99-2.08) and 1.64 per 100,000 (1.02-2.64) in North America and Europe, respectively, which were higher than individual estimates from the other regions.</p><p><strong>Conclusion: </strong>This review determined pooled, minimal diagnosed annual prevalence estimates for type I HAE, type II HAE, HAE-nC1-INH, and type I/II/nC1-INH combined. The pooled estimate for European countries was relatively higher than that for North American countries, as well as individually reported estimates in other regions. Nevertheless, valid comparisons across countries were hindered by a large degree of heterogeneity in data sources and diagnostic methodology. Additional, high-quality studies using standardized diagnostic methods are required to elucidate whether regional differences can be truly attributed to ethnic differences in phenotypic and genotypic variability.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1-14"},"PeriodicalIF":2.3,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13585417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of mir-224-5p by Targeting PTX3 Promotes Inflammatory Damage in Neonatal Pneumonia.","authors":"Dongqing Zhang, Huiqin Niu","doi":"10.1159/000553411","DOIUrl":"10.1159/000553411","url":null,"abstract":"<p><strong>Introduction: </strong>Neonatal pneumonia (NP) is one of the most serious infections affecting newborns. This study primarily investigates the diagnostic value and molecular mechanisms of miR-224-5p in NP.</p><p><strong>Methods: </strong>A total of 165 newborns were included, comprising 85 newborns with NP and 80 healthy newborns. miR-224-5p level was detected by RT-qPCR. miR-224-5p was overexpressed or inhibited in the WI38 cells treated with LPS by cell transfection. The target of miR-224-5p was predicted through bioinformatics analysis and validated by dual luciferase assays. Cell viability and apoptosis were assessed utilizing CCK-8 assays and flow cytometry. Inflammatory cytokine levels were measured by ELISA.</p><p><strong>Results: </strong>In NP, plasma miR-224-5p was downregulated and had significant diagnostic value (AUC = 0.877). miR-224-5p level was closely correlated with clinical indicators of NP. In the NP model, miR-224-5p increased cell viability, inhibited apoptosis, and alleviated inflammatory responses. PTX3 may be a downstream target of miR-224-5p. PTX3 may partially reverse the attenuation of inflammatory responses caused by miR-224-5p in NP.</p><p><strong>Conclusion: </strong>miR-224-5p may hold diagnostic potential in NP and may regulate inflammatory responses in NP by targeting PTX3.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1-10"},"PeriodicalIF":2.3,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Dupilumab in Eosinophilic Esophagitis: A Systematic Review and Meta-Analysis.","authors":"Roy Khalaf, Alexandre Ton That, Natacha Tardio, Waqqas Afif, Rilla Schneider, Moshe Ben-Shoshan","doi":"10.1159/000553602","DOIUrl":"10.1159/000553602","url":null,"abstract":"<p><strong>Introduction: </strong>Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disorder of the esophagus driven by type-2 inflammation. Dupilumab, a monoclonal antibody targeting the IL-4Ra subunit shared by the IL-4 and IL-13 receptor complexes, has recently emerged as a targeted biologic therapy for EoE. This systematic review evaluates the evidence for dupilumab in EoE across pediatric and adult populations, focusing on efficacy, safety, and symptom improvement.</p><p><strong>Methods: </strong>MEDLINE and Embase were searched from inception to June 30, 2025. Eligible studies included randomized controlled trials (RCTs), cohort studies, case-control studies, and case reports reporting dupilumab use in confirmed EoE. Study screening and quality assessment were performed in duplicate. Data on demographics, atopic comorbidities, dosing regimens, histologic outcomes, symptom improvement, and adverse events were extracted and summarized descriptively.</p><p><strong>Results: </strong>Nineteen studies (three randomized trials, nine cohorts, seven case reports) comprising 760 patients were included. Dupilumab was most commonly initiated following inadequate response or intolerance to proton pump inhibitors, swallowed corticosteroids, or dietary therapy. Across RCTs, histologic remission (≤15 eos/hpf) occurred in 60%-84% of dupilumab-treated patients versus <10% of placebo-treated patients. Cohort studies demonstrated comparable rates (68%-93%), with pediatric cohorts showing particularly robust responses (up to 90% remission). Meta-analysis using a random-effects logit model demonstrated a pooled histologic remission rate of 75.5% (95% CI: 67.4-82.1%) and a symptom improvement rate of 84.1% (95% CI: 77.8-88.9%).</p><p><strong>Conclusions: </strong>Dupilumab represents a promising therapeutic option, particularly for patients with inadequate response to proton pump inhibitor therapy, including those unable to maintain dietary restrictions. Future research should focus on predictors of response, durability of remission beyond 1 year, and comparative effectiveness relative to other therapies.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1-7"},"PeriodicalIF":2.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13485278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Significance of miR-766-3p in Severe Pneumonia in Children and Its Associated Molecular Mechanisms.","authors":"Weili Guo, Xiaoya Si, Zheng Ma, Jingxiao Zhao, Gailing Hao","doi":"10.1159/000552583","DOIUrl":"10.1159/000552583","url":null,"abstract":"<p><strong>Introduction: </strong>Severe pneumonia in children is a critical cause of childhood mortality. miR-766-3p is a known anti-inflammatory factor. The aim of our study is to investigate the clinical value of miR-766-3p and the molecular mechanisms by which miR-766-3p regulates severe pneumonia.</p><p><strong>Methods: </strong>The relative levels of miR-766-3p in participants' plasma were detected by quantitative real-time PCR (RT-qPCR). The diagnostic performance and prognostic value of miR-766-3p were assessed using receiver operating characteristic (ROC) curves, Kaplan-Meier curves, and Cox regression models. In vitro, lipopolysaccharide (LPS) was employed to mimic the pneumonia environment. Cell viability was tested by Cell Counting Kit-8 (CCK-8) assay. The levels of inflammatory factor were measured via RT-qPCR and enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>The levels of miR-766-3p were decreased by 0.36-fold in children with severe pneumonia, and it effectively distinguished between children with severe pneumonia and healthy children. In pediatric patients, the accumulative survival rate was lower in low miR-766-3p expression group (average miR-766-3p level ≤ 0.65) compared to high expression group (average miR-766-3p level > 0.65). Multivariable Cox proportional-hazards regression model analysis indicated that miR-766-3p was an independent risk factor for poor patient outcomes. Moreover, miR-766-3p mimic attenuated the inhibition of cell viability and interleukin-10 (IL-10) levels as well as the promotion of levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) caused by LPS. These effects were further abolished by Mucin 19 (MUC19) upregulation.</p><p><strong>Conclusion: </strong>miR-766-3p has potential as a diagnostic and prognostic biomarker. Mechanistically, miR-766-3p alleviates LPS-induced inflammation in MRC-5 cells by modulating MUC19.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1-12"},"PeriodicalIF":2.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRGPRX2 D184 Engagement by Food and Pollen Allergens: A Computational Hypothesis for IgE-Independent Mast-Cell Activation.","authors":"Yasuyuki Suzuki, Shuang Liu, Erika Takemasa, Masaki Mogi","doi":"10.1159/000553493","DOIUrl":"10.1159/000553493","url":null,"abstract":"<p><strong>Introduction: </strong>Some food and pollen allergic reactions, including anaphylaxis disproportionate to IgE titers, are not fully explained by IgE-mediated mechanisms. MRGPRX2, a polyspecific sensor of cationic ligands, mediates IgE-independent mast-cell degranulation and requires a salt bridge to aspartate D184. Whether protein allergens can adopt D184-engaging poses is unknown.</p><p><strong>Methods: </strong>Eleven peach, cedar pollen, peanut, birch, and yam allergens were docked against the experimental MRGPRX2 cryo-EM structure (PDB 7VV6) with HADDOCK3 under 3 protocols. Three agonists calibrated a D184 salt-bridge consistency threshold, four size-matched non-allergen proteins probed the determinants of engagement, and in silico mutagenesis tested D184 dependence.</p><p><strong>Results: </strong>Five allergens met a high-consistency threshold (≥2/3): Pru p 7, Cry j 7, Cry j 1, Pru p 3, and Ara h 6; Ara h 2 was moderate, and mature-chain Cry j 2 did not engage D184. Engagement was charge driven yet determined by a single accessible residue rather than net charge: HADDOCK score tracked the electrostatic term (ρ = 0.91) but not molecular weight (ρ = 0.27), the net-acidic Ara h 6 engaged through ARG4 while the net-neutral ubiquitin did not, and D184A abolished the salt bridge. Accordingly, size-matched non-allergen proteins presenting a surface lysine/arginine (ribonuclease A, carbonic anhydrase II) also formed genuine D184 salt bridges, whereas the acidic maltose-binding protein did not.</p><p><strong>Conclusion: </strong>Allergens presenting an accessible surface lysine or arginine can form the MRGPRX2 D184 salt bridge in agonist-like geometry, but engagement is governed by local cationic-residue accessibility rather than net charge or allergen identity - non-allergen proteins engage equally - so docking alone establishes neither specificity nor binding affinity, receptor activation, or clinical relevance. We propose a charge-based, exposure-gated hypothesis for experimental and clinical validation.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1-9"},"PeriodicalIF":2.3,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148436611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}