Clinical and Translational Allergy最新文献

{"title":"Biphasic, Refractory, and Persistent Anaphylaxis in Children.","authors":"Gizem Koken, H Ilbilge Ertoy Karagol, Sinem Polat Terece, Ceren Varer Akpinar, Kenan Cetin, Zeynep Cavdar, Berkehan Kara, A Kubra Baskin, Arzu Bakirtas","doi":"10.1002/clt2.70174","DOIUrl":"https://doi.org/10.1002/clt2.70174","url":null,"abstract":"<p><strong>Background: </strong>A Delphi consensus report refined anaphylaxis phenotypes as biphasic, refractory, and persistent anaphylaxis (BA, RA, and PA). To date, no study in either pediatric or adult populations has comprehensively evaluated the full spectrum of anaphylaxis phenotypes as outlined in this consensus. The primary aim of this study was to identify these phenotypes and compare them with conventional anaphylaxis in children.</p><p><strong>Methods: </strong>Patients aged ≤ 18 years who were diagnosed with or followed up for anaphylaxis at our department over the past 15 years were retrospectively screened for this study. All anaphylaxis cases were categorized as conventional anaphylaxis (Group 1) or as BA, RA, and PA phenotypes (Group 2). A comparative analysis was conducted between Group 1 and Group 2 with respect to demographics, triggers, clinical features, severity, management, and outcomes.</p><p><strong>Results: </strong>A total of 393 patients and 529 anaphylaxis episodes were included. Twenty-six (6.6%) of all anaphylaxis cases were classified as BA (3.5%), RA (1.5%), or PA (1.5%). For BA, the median time to recurrence of symptoms and signs was 4 h (1-24 h), whereas the median duration of PA manifestations was 4 h (4-6 h). These phenotypes (Group 2) were more common in older children and were associated with increased cardiovascular manifestations, greater severity, and higher use of systemic corticosteroid (p < 0.001). They did not differ significantly from Group 1 with respect to gender, comorbidities, family history of atopy, timing or location of the anaphylaxis, or number of episodes. Drugs, followed by venoms, were more frequent triggers in Group 2, whereas food was significantly more common in Group 1 (p < 0.05). IM adrenaline was administered in 69.2% of Group 2% and 52.3% of Group 1, with no significant difference (p > 0.05). Comparisons among BA, RA, and PA could not be performed due to the limited sample size within each phenotype.</p><p><strong>Conclusions: </strong>BA, RA, and PA are rare anaphylaxis phenotypes, more frequently drug or venom induced, seen at older ages, with ongoing gaps in proper IM adrenaline use.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"16 5","pages":"e70174"},"PeriodicalIF":4.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of Patch Testing, LTT, and HLA Genotyping in Identifying Culprit Drugs and Diagnosing Multiple Drug Hypersensitivity in Definite DRESS: A 10-Year Cohort Study.","authors":"Derya Ünal, Osman Ozan Yeğit, Semra Demir, Bircan Erden, Pelin Korkmaz, Fatma Savran Oğuz, Çiğdem Kekik Çınar, Sonay Temurhan, Deniz Eyice Karabacak, Ilkim Deniz Toprak, Zeynep Kılınç, Mehmet Sait Yordam, Nevzat Kahveci, Merve Hörmet İğde, Şule Çelik Kamacı, Ayşe Feyza Aslan, Mehmet Emin Sezgin, Esra Kaya, Leyla Bölek, Raif Coşkun, Müge Olgaç, Nida Öztop, Aslı Gelincik","doi":"10.1002/clt2.70172","DOIUrl":"https://doi.org/10.1002/clt2.70172","url":null,"abstract":"<p><strong>Background/aim: </strong>We evaluated the role of lymphocyte transformation test (LTT), patch testing (PT), and human leukocyte antigen (HLA) genotyping in identifying culprit drugs in Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and assessed long-term outcomes.</p><p><strong>Methods: </strong>DRESS was diagnosed using Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) criteria; only definite cases (score > 5) were included. Severe DRESS was defined as ≥ 1 major organ involvement with clinical and laboratory abnormalities, and RegiSCAR scores supported severity assessment. Patients were grouped by single- or multiple drug exposure. Drug causality was assessed using the WHO-UMC criteria. LTT, PT, and/or HLA genotyping were performed for \"possible\" culprit drugs. Multiple drug hypersensitivity syndrome (MDHS) was defined as hypersensitivity to ≥ 2 unrelated drugs confirmed by testing. Hypersensitivity to a single drug was classified as single-drug hypersensitivity (SDH). Long-term follow-up assessed autoimmune diseases and neo-sensitization to unrelated drugs.</p><p><strong>Results: </strong>Fifty patients with definite DRESS (median age 49 years; 50% were female) were included, and six (12%) had severe disease. Compared with non-severe cases (mild/moderate), severe cases had higher median RegiSCAR scores (8 [7-8] vs. 6 [6-7]; p = 0.012) and more frequent facial edema (p < 0.001) and lymphadenopathy (p = 0.029). MDHS was more common in severe cases (83% vs. 11%; p = 0.001), and HLA risk alleles were more prevalent (p = 0.016), including HLA-B*58:01, HLA-A*31:01, and HLA-B*13:02, associated with allopurinol, carbamazepine, and levofloxacin-induced DRESS, respectively. Among 20 patients with multiple drug exposures, 10 were diagnosed with MDHS: 5 simultaneous, 2 sequential, and 4 long-interval; one patient exhibited both simultaneous and long-interval reactions. Compared with SDH, MDHS patients had higher median RegiSCAR scores (7 [6-8] vs. 6 [6-8]; p < 0.001) and a higher prevalence of HLA risk alleles (p = 0.038), including HLA-B*58:01 (allopurinol), HLA-A*31:01 (carbamazepine), HLA-B*13:02 (levofloxacin) and HLA-A*24:02 (lamotrigine). Long-term complications occurred in eight patients: four developed autoimmune diseases, and four had neo-sensitization leading to subsequent DRESS, considered long-interval MDHS.</p><p><strong>Conclusion: </strong>PT and LTT effectively identified culprit drugs in DRESS, particularly in multiple drug exposure. MDHS was more frequent in severe DRESS and associated with a higher prevalence of drug-related HLA risk alleles; however, no single HLA marker defined MDHS. Long-term follow-up was essential to detect autoimmune sequelae and neo-sensitization, and to guide safe drug evaluation and reintroduction.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"16 4","pages":"e70172"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Remission in Severe T2-High Asthma in Real Life After Anti-IgE, Anti-IL-5 and Anti-IL5R: A Potential Role for CRP as a Biomarker.","authors":"Jeanne Vervier, Marie Sabbe, France Louis, Catherine Moermans, Françoise Guissard, Carole Sanchez, Virginie Paulus, Monique Henket, Genevieve Philippe, Casper W H Beijnink, Pierre-Olivier Bridevaux, Florence Schleich, Renaud Louis","doi":"10.1002/clt2.70164","DOIUrl":"10.1002/clt2.70164","url":null,"abstract":"<p><strong>Background: </strong>Biotherapies have transformed the management of severe asthma (SA), shifting treatment goals from disease control toward achieving clinical remission. This study aimed to evaluate the effectiveness of biotherapies in inducing remission in severe asthma and to identify baseline patient characteristics that could predict remission.</p><p><strong>Methods: </strong>We conducted an observational, retrospective, monocentric study including severe T2-high asthmatic patients who had initiated their first biological therapy (omalizumab, mepolizumab or benralizumab) between 2006 and 2023. Clinical remission at 12 months was defined by the absence of exacerbations, no chronic oral corticosteroid use, and good symptom control (Asthma Control Test score ≥ 20 and Asthma Control Questionnaire-6 score < 1.5).</p><p><strong>Material: </strong>Data were extracted from the registry of our asthma clinic. We included 206 patients-97 treated with omalizumab, 71 with mepolizumab, and 38 with benralizumab.</p><p><strong>Results: </strong>Of the 206 patients, 62 (30%) achieved remission at 12 months. The mean age was 52 years, and 39% were male. Remission rates were 29% for omalizumab, 28% for mepolizumab, and 37% for benralizumab. Patients achieving remission had better baseline lung function (pre- and post-bronchodilator FEV1% predicted and FVC % predicted, p = 0.01), lower CRP levels (p = 0.01), earlier disease onset (p < 0.05), and were less likely to have a history of smoking (p < 0.01) and denied SABA and LAMA use compared to patients who did not achieve remission. Only CRP remained significant predictor after multiple logistic regression (p = 0.04).</p><p><strong>Conclusion: </strong>Biological treatments with omalizumab, mepolizumab or benralizumab are capable of inducing clinical remission at 12 months in around one third of severe T2-high asthmatics. A low baseline CRP might be predictive of achieving remission.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"16 4","pages":"e70164"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13084146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basophil FCER1A and PTAFR Gene Expression Profiles Correlate With Disease Severity in Chronic Spontaneous Urticaria.","authors":"Kevin Muliawan Soetanto, Chattip Sripatumtong, Teerapat Paringkarn, Nattha Angkoolpakdeekul, Kanokvalai Kulthanan, Yuttana Srinoulprasert","doi":"10.1002/clt2.70168","DOIUrl":"10.1002/clt2.70168","url":null,"abstract":"<p><strong>Background: </strong>Chronic Spontaneous Urticaria (CSU) is a debilitating skin condition characterized by recurrent wheals and pruritus, significantly impacting quality of life. Molecular mechanisms underlying different severity phenotypes are not fully understood. This study aimed to investigate the expression of FCER1A and PTAFR genes in basophils implicated in CSU pathogenesis from CSU patients with varying disease severities.</p><p><strong>Methods: </strong>We recruited 45 CSU patients, stratified into mild (n  =  15), moderate (n  =  15), and severe (n  =  15) groups, and 15 healthy controls. Basophils were isolated from peripheral blood, and the relative mRNA expression of FCER1A and PTAFR genes was quantified using real-time PCR.</p><p><strong>Results: </strong>CSU patients exhibited significantly higher expression levels of FCER1A and PTAFR genes compared to healthy controls. FCER1A expression was significantly elevated in all CSU groups compared to controls and was higher in moderate and severe groups than in the mild group. PAFR expression was also significantly higher in moderate and severe CSU. Correlation analysis revealed that both FCER1A and PTAFR mRNA expression levels positively correlate with CSU severity.</p><p><strong>Conclusion: </strong>The expression of FCER1A and PTAFR genes in basophils correlates significantly with CSU severity, suggesting their potential as both prognostic and severity biomarkers. These findings highlight key molecular pathways that could be targeted for therapeutic intervention. Early detection of elevated gene expression could facilitate timely, targeted treatments, potentially reducing the progression to severe disease in CSU patients.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"16 4","pages":"e70168"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AllergoOncology: Emerging Translational and Clinical Significance of Basophils and Mast Cells in Cancer.","authors":"Jack Alder, Katie E Lacy, Debra H Josephs, James Spicer, Heather J Bax, Sophia N Karagiannis, Jitesh Chauhan","doi":"10.1002/clt2.70170","DOIUrl":"10.1002/clt2.70170","url":null,"abstract":"<p><p>Mast cells and basophils, historically defined by their pathogenic roles in allergic diseases and type I hypersensitivity, are increasingly recognized as influential participants in cancer biology. Emerging research in AllergoOncology highlights their plasticity, diverse functions, and significance beyond classical contributions to allergy. This review summarizes current evidence on their presence, activation states, and roles across multiple cancer types. We examine their interactions with other immune populations, their context-dependent pro- and anti-tumor functions, and their potential utility as biomarkers. Their pro-tumor activities include secretion of Th2 cytokines, release of angiogenic mediators, and facilitation of extracellular matrix remodeling, all of which can support tumor progression. Conversely, these cells may also promote anti-tumor immunity through effector mechanisms and recruitment of cytotoxic CD8⁺ T cells. Translational tools such as the basophil activation test (BAT) and the mast cell activation test (MAT) are emerging to help predict hypersensitivities to cancer treatments including immunotherapies. A deeper understanding of their dynamic roles within the tumor microenvironment (TME) and across anatomical locations may reveal previously underappreciated functions, prognostic value, and therapeutic opportunities.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"16 4","pages":"e70170"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13086569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrastructural Mucosal Response to Dupilumab in Chronic Rhinosinusitis With Nasal Polyps: A Pilot Study.","authors":"Francesco Giombi, Gian Marco Pace, Elena Vezzoli, Fabio Grizzi, Fabio Pasqualini, Michele Cerasuolo, Enrico Heffler, Giovanni Paoletti, Francesca Puggioni, Giuseppe Mercante, Giuseppe Spriano, Giorgio Walter Canonica, Luca Malvezzi","doi":"10.1002/clt2.70173","DOIUrl":"https://doi.org/10.1002/clt2.70173","url":null,"abstract":"<p><strong>Background: </strong>As monoclonal antibodies have proven effective in managing recalcitrant chronic rhinosinusitis with nasal polyps (CRSwNP), the concept of disease remission is evolving, underscoring the need for a comprehensive, multimodal evaluation of disease burden over time.</p><p><strong>Objective: </strong>This study first presents ultrastructural changes of the nasal epithelium in patients treated with dupilumab, assessing the potential for mucosal regeneration during long-term follow-up.</p><p><strong>Methods: </strong>Ten patients (n = 10) were enrolled. Baseline (T0) outcomes included Nasal Polyp Score, Lund-Kennedy Score, 22-item Sinonasal Outcome Test, Visual Analog Scale for nasal symptoms, and CT-scan Lund-Mackay Score. Mucosal samples were collected from the posteromedial aspect of prior antrostomies and analyzed using both light microscopy and transmission electron microscopy (TEM). Outcomes and mucosal sampling were reassessed at 12-month (T1) and compared. Logistic bivariate analysis was performed to assess the relationship between ultrastructural tissue characteristics and clinical outcomes.</p><p><strong>Results: </strong>Significant improvements in all outcomes were observed at T1. A ciliated columnar epithelium was identifiable in most patients (n = 7/10). Intercellular junctions, including desmosomes, tight and adherens junctions, were evident in half of the sample (n = 5/10). Three patients (n = 3/10) showed no evidence of epithelial regrowth. Endoscopic and radiologic outcomes were significantly linked to ultrastructural findings at T1. Higher eosinophilic infiltration at T0 was a positive predictor for the presence of pseudostratified epithelium at T1.</p><p><strong>Conclusions: </strong>These first preliminary data suggest that ultrastructural response is achievable in most patients with CRSwNP. Larger cohorts are required to strengthen these findings and support the concept of disease remission in course of mAb.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"16 4","pages":"e70173"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations Between Different Eosinophil Activity Markers and Clinical Outcomes in Young Asthmatics","authors":"Nils Oskar Jõgi,&nbsp;Nikolaos Tsolakis,&nbsp;Anders Sjölander,&nbsp;Robert Movérare,&nbsp;Christer Janson,&nbsp;Andrei Malinovschi,&nbsp;Kjell Alving","doi":"10.1002/clt2.70167","DOIUrl":"10.1002/clt2.70167","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Identifying biomarkers for different aspects of asthma morbidity is crucial for effective disease monitoring and management. The performance of fractional exhaled nitric oxide (FeNO), blood eosinophil count (BEC), and eosinophil activity markers should be evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to compare the associations of FeNO, BEC, serum and plasma eosinophil-derived neurotoxin (S- and P-EDN), and serum eosinophilic cationic protein (S-ECP) with important clinical outcomes in asthma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In total, 390 individuals aged 10–35 years with physician-diagnosed asthma were included. Asthma control test (ACT), spirometry, and methacholine challenge tests were used to assess asthma morbidity. The biomarkers' associations with asthma outcomes: impaired spirometry (FEV₁ &lt; 80% predicted, FEV₁/FVC &lt; lower limit of normal), airway hyperresponsiveness (AHR), uncontrolled asthma (ACT &lt; 20) were analysed with multiple logistic regression models adjusted for body mass index, sex, age, immunoglobulin E sensitisation, smoking, and controller medication. The Akaike information criterion (AIC) was calculated for each model, to compare biomarker performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>S-EDN had the lowest AIC value of all biomarkers in models assessing the association with reduced lung function, showing better model fit than P-EDN and S-ECP. However, FeNO and BEC had the lowest AIC values for AHR. FeNO was the only biomarker associated with uncontrolled asthma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>S-EDN may serve as an alternative to BEC in research setting and could be relevant in assessing airway obstruction. However, adding S-EDN as a routine biomarker alongside FeNO and BEC may offer limited additional clinical value. Further research in larger cohorts is needed to validate these findings and establish optimal cut-offs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"16 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Outcome Associated With Beta-Lactam Allergy Labels in Hospitalized Patients in Belgium","authors":"Liesbeth Gilissen,&nbsp;Greet Van De Sijpe,&nbsp;Annouschka Laenen,&nbsp;Peter Declercq,&nbsp;Dries Wets,&nbsp;Ileana Ghiordanescu,&nbsp;Anca Mirela Chiriac,&nbsp;Willy E. Peetermans,&nbsp;Paul De Munter,&nbsp;Isabel Spriet,&nbsp;Rik Schrijvers","doi":"10.1002/clt2.70166","DOIUrl":"10.1002/clt2.70166","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In the United States, beta-lactam allergy labels (BLAL) are documented in 9%–16% of hospitalized patients and associated with worse clinical outcomes such as increased mortality, length of hospital stay (LOS), intensive care unit (ICU) admission, and use of alternative antibiotics, providing an incentive for broad delabeling protocols. In Europe, BLAL prevalences are lower (0.6%–5%) and the association with clinical outcomes insufficiently explored. Therefore, we assessed the association between BLAL and penicillin allergy label (PenAL) and clinical outcomes and antibiotic use in hospitalized patients in Belgium.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retrospective population-based cohort study of all patients admitted to the University Hospitals Leuven between 2010 and 2018 for pneumonia, pyelonephritis (therapeutic indications), or appendectomy, coronary artery bypass grafting, total knee or hip replacement (prophylactic indications) or heart, kidney, liver, or lung transplantation (mixed indications). Multivariable regression analysis was performed, using BLAL or PenAL as independent variable, and age, gender, Charlson Comorbidity Index, and diagnosis as a priori hypothesized confounders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 21,999 patients accounting for 23,842 admissions. A BLAL was recorded in 1394 (6.3%) patients, with 1113 (5.1%) having an unspecified PenAL. An increased use of next-line antibiotics was observed among patients with BLAL or PenAL. However, BLAL or PenAL were not associated with altered in-hospital or 3-month post-hospitalization mortality, LOS or ICU admission.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Despite altered antibiotic use, we observed no association of BLAL or PenAL with clinical outcome parameters, highlighting regional differences and limiting transferability of non-EU findings to guide EU delabeling protocols.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"16 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70166","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-25 Disrupts the Nasal Epithelial Barrier in an Adapter Act1-Dependent Manner","authors":"Baodan Zhang,&nbsp;Shenting Li,&nbsp;Qiqi Wang,&nbsp;Su Duan,&nbsp;Luo Zhang","doi":"10.1002/clt2.70165","DOIUrl":"10.1002/clt2.70165","url":null,"abstract":"&lt;p&gt;To the editor:&lt;/p&gt;&lt;p&gt;Chronic rhinosinusitis (CRS) has become a significant public health issue that notably affects people’s health worldwide. The study further classifies CRS into localized type and diffuse type. Based on the differences in the intrinsic inflammatory response mechanisms of various types of lesions, diffuse CRS can be divided into eosinophilic CRS (eCRS) and non-eosinophilic CRS (non-eCRS), while the original diagnosis of chronic rhinosinusitis with nasal polyps (CRSwNP) is incorporated into diffuse CRS [&lt;span&gt;1&lt;/span&gt;]. Each of the two aforementioned types of sinusitis can be further subdivided into two subtypes: with and without nasal polyps. Of these, the subtype with nasal polyps is strongly linked to epithelial barrier dysfunction and tissue hyperplasia driven by persistent chronic inflammation, and is also more refractory to curative therapy. In recent years, the concept of eosinophilic inflammation has been gradually evolving into the concept of type 2 inflammation [&lt;span&gt;1&lt;/span&gt;]. Epithelial cells are a key regulatory hub in type 2 inflammatory networks: they are both targets of inflammatory injury and sensor-secretory effectors. The barrier disruption by allergens, pathogens, or physicochemical insults prompts their rapid secretion of epithelium-derived type 2 cytokines, which activate ILC2s and dendritic cells to initiate innate type 2 inflammatory responses. Meanwhile, IL-13 from Th2 cells and ILC2s induces epithelial phenotypic remodeling, exacerbating tissue damage and forming a self-sustaining inflammatory vicious cycle—initial epithelial barrier impairment triggers inflammatory signaling, which in turn further disrupts the barrier [&lt;span&gt;2&lt;/span&gt;]. An intact and functional epithelial barrier characterized by tight junctions (TJs) plays a crucial defensive role in resisting the invasion of pathogens and pollutants. Zonula occludens-1 (ZO-1) is recognized as an essential core protein component of epithelial and endothelial tight junctions. Impairment in the structure and function of epithelial TJs is closely associated with the pathogenesis of chronic rhinosinusitis with nasal polyps.&lt;/p&gt;&lt;p&gt;IL-25, as an inflammatory mediator in a variety of inflammatory responses, is closely associated with the occurrence of asthma, atopic dermatitis, and psoriasis. First identified in 2001, IL-25 is mapped to chromosome 14q11 and belongs to the IL-17 cytokine family. Target cells, which encompass diverse epithelial cell populations within interface tissues including the respiratory tract, gastrointestinal tract, genitourinary tract, skin and nasal mucosa (comprising ciliated epithelial cells, goblet cells, and basal epithelial cells), are the primary sites where IL-25 initially binds to its cognate receptor interleukin-17 receptor homolog 1 (IL-17Rh1) to form a functional complex [&lt;span&gt;3, 4&lt;/span&gt;]. The process by which IL-25 induces diseases through disrupting the epithelial barrier has been extensively and thoroughly investig","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"16 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Disulfidptosis in the Local Inflammatory Response of Atopic Dermatitis","authors":"Dong-Mei Zhou,&nbsp;Cheng Chen,&nbsp;Yuan-Fen Liao,&nbsp;Xi-Meng Ma,&nbsp;Xin-Hui Gong,&nbsp;Cheng-Jun Cui,&nbsp;Yu-Bao Cui","doi":"10.1002/clt2.70163","DOIUrl":"10.1002/clt2.70163","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Understanding cell death pathways is critical for elucidating the mechanisms underlying inflammation in atopic dermatitis (AD). This study investigates the role of disulfidptosis, a novel form of programmed cell death, in AD pathogenesis.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;RNA-seq datasets GSE193309 and GSE121212 from GEO were analyzed to examine 43 disulfidptosis-related genes. Differentially expressed genes (DEGs) were identified using the limma package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to annotate biological functions and signaling pathways. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to identify gene modules significantly associated with AD. A protein-protein interaction (PPI) network was constructed using STRING data, and further visualized and analyzed with Cytoscape to identify core mRNA-pathway relationships involving disulfidptosis. Key disulfidptosis-related mRNAs were validated in the dataset GSE121212. Following house dust mite (HDM) extract treatment, disulfidptosis was induced in HaCaT cells, with characteristic F-actin collapse visualized by confocal microscopy and redox imbalance confirmed by an increased NADP&lt;sup&gt;+&lt;/sup&gt;/NADPH ratio. Expression of disulfidptosis-related genes was quantified via RT-qPCR.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A total of 4239, 3570, and 516 DEGs were identified between lesional skin (LS) and healthy control (HC), LS and non-lesional skin (NL), and NL and HC, respectively. WGCNA clustered these DEGs into 14 co-expression modules, five of which were significantly correlated with AD. Notably, the turquoise module showed the strongest association with LS and contained four disulfidptosis-related genes: &lt;i&gt;ACTB&lt;/i&gt;, &lt;i&gt;GYS1&lt;/i&gt;, &lt;i&gt;SLC7A11&lt;/i&gt;, and &lt;i&gt;MYH9&lt;/i&gt;. These four genes were consistently upregulated in LS compared to both NL and HC. Immunofluorescence staining showed F-actin contraction and membrane detachment in HDM-treated HaCaT cells, consistent with disulfidptotic morphology. A significant increase in the NADP&lt;sup&gt;+&lt;/sup&gt;/NADPH ratio further supported disulfidptosis induction. qPCR confirmed upregulation of four key disulfidptosis-related genes (&lt;i&gt;ACTB&lt;/i&gt;, &lt;i&gt;GYS1&lt;/i&gt;, &lt;i&gt;SLC7A11&lt;/i&gt;, and &lt;i&gt;MYH9&lt;/i&gt;) in response to HDM exposure. Moreover, HDM treatment triggered a pronounced pro-inflammatory response, as evidenced by the elevated mRNA expression of cytokines IL-25, IL-33, TSLP, IL-6, and IL-8.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Our finding","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"16 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}