Clinical and Experimental Allergy最新文献

{"title":"Exploratory Safety Evaluation of Dupilumab Combined With Subcutaneous Immunotherapy in House Dust Mite-Sensitised Patients With Atopic Dermatitis: A Retrospective Case Series From Northern China.","authors":"Xu Li, Yanfei Li, Junjing Zhang, Shuang Wu, Liya Ai, Xin Tong, Change Fan, Huijiao Cai, Jingxue Guo, Tingting Gao, Peize Liu, Na Liu, Peng Jin, Lili Zhi","doi":"10.1111/cea.70077","DOIUrl":"https://doi.org/10.1111/cea.70077","url":null,"abstract":"<p><p>Patients with atopic dermatitis (AD) are frequently sensitised to house dust mites (HDM). While Dupilumab is effective, the role of subcutaneous immunotherapy (SCIT) remains unclear. This study evaluated the safety and clinical outcomes of combined Dupilumab and SCIT in HDM-sensitised AD patients. In this retrospective study, 47 adults with HDM-sensitised AD received concurrent Dupilumab and HDM-SCIT for 48 weeks. Eczema Area and Severity Index (EASI) scores, total and HDM-specific IgE levels were monitored. Safety was assessed by adverse events related to SCIT and Dupilumab. EASI scores improved significantly from baseline (28.4 ± 6.9) to Week 12 (14.8 ± 4.5), Week 24 (12.7 ± 4.3) and Week 48 (5.2 ± 2.8). HDM-specific IgE (d1, d2) and total IgE decreased by Week 48 (p < 0.05). SCIT-related local and systemic reactions declined over time. Dupilumab-related conjunctivitis, head and neck dermatitis, and upper respiratory tract infections were transient and reduced during follow-up. The combination of Dupilumab and SCIT was well tolerated and associated with clinical improvement and IgE reduction in HDM-sensitised AD patients. These findings support further investigation in prospective controlled trials.</p>","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spectrum and Impact of Reported Side Effects of Omalizumab in Patients With Chronic Urticaria: A Long-Term Multicentre Real-World Study","authors":"Reineke Soegiharto,&nbsp;Esther Van der Wind,&nbsp;Mehran Alizadeh Aghdam,&nbsp;Jennifer A. Sørensen,&nbsp;Esmee Van Lindonk,&nbsp;Ferhan Bulut Demir,&nbsp;Nasser Mohammad Porras,&nbsp;Yoshimi Matsuo,&nbsp;Lea Kiefer,&nbsp;André C. Knulst,&nbsp;Marcus Maurer,&nbsp;Carla Ritchie,&nbsp;Michael Rudenko,&nbsp;Emek Kocatürk,&nbsp;Roberta Fachini Jardim Criado,&nbsp;Stamatis Gregoriou,&nbsp;Tatjana Bobylev,&nbsp;Andreas Kleinheinz,&nbsp;Shunsuke Takahagi,&nbsp;Michihiro Hide,&nbsp;Ana M. Giménez-Arnau,&nbsp;Andaç Salman,&nbsp;Rabia Oztas Kara,&nbsp;Bahar Sevimli Dikicier,&nbsp;Martijn B. A. Van Doorn,&nbsp;Simon F. Thomsen,&nbsp;Juul M. P. A. Van den Reek,&nbsp;Heike Röckmann","doi":"10.1111/cea.70067","DOIUrl":"10.1111/cea.70067","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;Chronic urticaria (CU) treatment with omalizumab is considered safe in short-term studies. Large real-world studies focusing on the long-term safety of omalizumab and associated factors are lacking. We aimed to investigate the spectrum of reported side effects in omalizumab-treated CU patients in a large long-term daily practice cohort.&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;A multinational multicentre retrospective study was conducted at 14 specialised urticaria centres (UCAREs), including all CU patients ever treated with omalizumab until centre-specific data lock. The prevalence of patient-reported side effects was assessed.&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 1859 patients were included, of which 32.9% (&lt;i&gt;n&lt;/i&gt; = 612) reported side effects during omalizumab treatment with a wide range across centres (0%–75.5%). Fatigue (15.8%, &lt;i&gt;n&lt;/i&gt; = 293), headache (11.6%, &lt;i&gt;n&lt;/i&gt; = 215) and flu-like symptoms (9.3%, &lt;i&gt;n&lt;/i&gt; = 172) were most common. No events suggestive of anaphylaxis and no new notably prevalent side effects were reported. Hair loss was reported by 2.9% (&lt;i&gt;n&lt;/i&gt; = 53/1859) of patients, leading to treatment adjustment in 21.1% (&lt;i&gt;n&lt;/i&gt; = 8/38 with sufficient data). Patients who reported side effects were more often female (78.3% vs. 68.6%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), had worse disease control prior to omalizumab (Urticaria Control Test, UCT, 4.0 vs. 6.0, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), and lower fast response (Weekly Urticaria Activity Score, UAS7, &lt; 7 or UCT &gt; 11 within 4 weeks, 42.6% vs. 59.5%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) and complete/good response rates (UAS7 &lt; 7 or UCT &gt; 11 at end of treatment, 72.3% vs. 84.4%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) compared to patients without side effects. While only 2.4% (&lt;i&gt;n&lt;/i&gt; = 44/1859) of patients discontinued treatment due to side effects, 5.5% (&lt;i&gt;n&lt;/i&gt; = 100/1859) and 12.8% (&lt;i&gt;n&lt;/i&gt; = 238/1859) of patients reporting side effects with insufficient (UAS7 ≥ 7 or UCT 3–11 at end of treatment) and complete/good response, respectively, remained on omalizumab.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The safety and tolerability of omalizumab was confirmed. Notably, the wide variation in reported side effects across centres suggests that differences in awareness influence reporting. Hair loss was more prevalent than described before, warranting extra attention. Side effects were more often reported in patients whose characteristics suggest reduced effectiveness of omalizumab, possibly related to a negative association with omalizumab and suggestin","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 6","pages":"481-492"},"PeriodicalIF":6.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cea.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993271","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":"Correction to Water hardness and atopic dermatitis in the first year of life in the New Hampshire Birth Cohort Study","authors":"","doi":"10.1111/cea.70070","DOIUrl":"10.1111/cea.70070","url":null,"abstract":"<p>Ezzamouri B, Palys TJ, Jackson BP, Coto SD, Madan JC, Flohr C, Karagas MR, Peacock JL. Water hardness and atopic dermatitis in the first year of life in the New Hampshire Birth Cohort Study. Clin Exp Allergy. 2023 Mar;53(3):362–366. doi: 10.1111/cea.14272. PMID: 36541020.</p><p>There was an error in the computation of calcium carbonate (CaCO₃) which has affected all analyses that included CaCO₃.</p><p>The corrected median CaCO₃ is 67.3 mg/L with interquartile range 32–114. These replace the values reported in the text of the paper. Table 1 included eczema by various characteristics including CaCO₃; eczema prevalence by CaCO₃ quartiles, corrected, is given in the (partial) table 1 below.</p><p>Table 2 reported odds of eczema in the presence of an interaction of CaCO₃ by family history of eczema. These models have been re-run using the corrected CaCO₃ values (see table 2 corrected below).</p><p>In the text, estimated odds ratios (OR) are reported for the group of children living in areas with a high level of CaCO₃ and who had a family history of eczema. Using the corrected table 2 values these are corrected to i) <i>any eczema</i> (OR = 1.68; 95% CI 0.97–2.96), with a significant trend (<i>p</i> = 0.02) and ii) <i>eczema lasting more than 2 days</i> (1.63; 95% CI 0.92–2.87), test for trend, <i>p</i> = 0.20.</p><p>The OR and 95% CIs for these analyses were similar following multiple imputation of missing data, with corrected values: 1.48 (0.8–2.13) for <i>any eczema</i> and 1.44 (0.7–2.02) for <i>eczema lasting more than 2 days</i>.</p><p>We note that while model estimates have changed slightly, the overall trends, interpretation and conclusions are unchanged.</p><p>The corrected <i>Additional Information</i> can be found at:</p><p>\u0000 https://osf.io/ukzm5/files/osfstorage/67fe5df52fe33ed79bd56627\u0000 </p><p>We sincerely apologize for this error.</p>","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 7","pages":"594-595"},"PeriodicalIF":6.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cea.70070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968822","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":"Roadmap of Anaphylaxis Registries Across the World.","authors":"Guillaume Pouessel, François Dubos, Stéphanie Lejeune, Diane Pelletier de Chambure, Paul-Michel Mertes, Charles Tacquard, Sébastien Lefevre, Pascal Demoly, Luciana Kase Tanno","doi":"10.1111/cea.70074","DOIUrl":"https://doi.org/10.1111/cea.70074","url":null,"abstract":"","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-Year Longitudinal Evaluation of Timing Effects on Subcutaneous Immunotherapy Efficacy and Safety in Allergic Rhinitis.","authors":"Hang Li, Xiaomei Yang, Yihui Wen, Dehua Chen, Xiumin Chen, Minghao Pan, Changhui Chen, Huimin Chen, Xingyu Lin, Wen Lyu, Wenbin Lei, Weiping Wen, Rui Xu","doi":"10.1111/cea.70075","DOIUrl":"https://doi.org/10.1111/cea.70075","url":null,"abstract":"","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Airway Basal Stem Cell Population Is Enlarged in Bronchial Thermoplasty Treated Airways in Severe Asthma Patients","authors":"Tessa E. Gillett,&nbsp;Sofi M. Vassileva,&nbsp;Els Weersink,&nbsp;Jouke Annema,&nbsp;René Lutter,&nbsp;Martijn C. Nawijn,&nbsp;Maarten van den Berge,&nbsp;Peter I. Bonta,&nbsp;Abilash Ravi","doi":"10.1111/cea.70071","DOIUrl":"10.1111/cea.70071","url":null,"abstract":"&lt;p&gt;Approximately 5% of asthma patients have severe disease, not well-controlled [&lt;span&gt;1&lt;/span&gt;] and are treated using biologicals and/or bronchial thermoplasty (BT) [&lt;span&gt;2&lt;/span&gt;]. BT applies temperature-controlled radio-frequency energy to medium-sized and larger airways to impact airway remodelling, including reduction of airway smooth muscle and changes in extra-cellular matrix, leading to improved asthma-related quality of life and reduced exacerbations [&lt;span&gt;3&lt;/span&gt;]. We previously demonstrated that BT alters metabolism [&lt;span&gt;4&lt;/span&gt;] and reduces inflammation [&lt;span&gt;5&lt;/span&gt;] in bronchial brushes subjected to RNA-sequencing. During epithelial injury, basal cells can self-renew, differentiate, and drive immune responses along with macrophages and dendritic cells. BT-induced changes in the cell type composition of the bronchial epithelium are unknown. To investigate this, we performed cell type deconvolution on bulk RNA-sequencing data from bronchial brushes collected in the TASMA study [&lt;span&gt;6&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The TASMA study performed an extensive clinical characterisation and samples were collected before and 6 months after BT, in treated airways and at 6 months in the untreated right middle lobe, but not before from the same subjects. Bronchial brushes were obtained from severe asthma patients (&lt;i&gt;n&lt;/i&gt; = 23) in the segmental and subsegmental bronchi and contain sub-types of bronchial epithelium, along with alveolar macrophages, dendritic cells and lymphocytes. The TASMA study design, inclusion and exclusion criteria and methods have been previously described [&lt;span&gt;6&lt;/span&gt;]. The study was approved by the Medical Ethics Committee and all subjects gave their written informed consent (NL45394.018.13) [&lt;span&gt;6&lt;/span&gt;]. Cell type deconvolution was performed with CIBERSORTx, using single cell RNA-sequencing data of bronchial brushes from the Human Lung Cell Atlas as a reference. Accuracy was validated by deconvolution of HLCA-derived bronchial brush pseudobulk samples of known cell type composition. Additional information on patient characteristics, sample collection, RNA isolation, sequencing and deconvolution analysis are available in the following repository: https://zenodo.org/records/14857109.&lt;/p&gt;&lt;p&gt;Deconvolution analysis estimated proportions of basal (15.49%), ciliated lineage (ciliated and deuterosomal cells;79.47%), secretory (0.15%), and rare (ionocytes, neuroendocrine and tuft cells;0.24%) epithelial cells, monocytes (0.87%), alveolar (1.78%) and luminal macrophages (0.25%), dendritic cells (1.47%), mast cells (0.23%), B-cell lineage cells (B- and plasma cells;0.05%), and T-, NK and innate lymphoid cells (0.06%) in bronchial brushes of all samples (Figure 1A). We excluded cell types with an estimated proportion of zero in more than 60% of the samples from further statistical analyses. Six months after BT, we found estimated basal cell proportions to be significantly higher in treated compared to untreated regions, from the sam","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 9","pages":"880-882"},"PeriodicalIF":5.2,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cea.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970848","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":"Variants of the MRGPRX2 Gene Found in Patients With Hypersensitivity to Quinolones and Vancomycin Show Amplified and Drug-Specific Activation Responses In Vitro","authors":"Paola Leonor Quan,&nbsp;Laia Ollé,&nbsp;Marina Sabaté-Bresco,&nbsp;Elizabeth Guruceaga,&nbsp;José Julio Laguna,&nbsp;Inmaculada Doña,&nbsp;Rosa Muñoz-Cano,&nbsp;José Luis Perez-Gracia,&nbsp;Margarita Martín,&nbsp;Gabriel Gastaminza","doi":"10.1111/cea.70068","DOIUrl":"10.1111/cea.70068","url":null,"abstract":"&lt;p&gt;The diagnosis of immediate hypersensitivity reactions (IHDRs) to fluoroquinolones and vancomycin is challenging. Though they may be partially mediated by the immunoglobulin E (IgE) high-affinity receptor in mast cells [&lt;span&gt;1, 2&lt;/span&gt;], key features suggest that other mechanisms could be at play [&lt;span&gt;2, 3&lt;/span&gt;]. They often occur in drug-naïve individuals [&lt;span&gt;1, 4&lt;/span&gt;] receiving first doses of treatment [&lt;span&gt;1, 4&lt;/span&gt;], and skin testing results are frequently unreliable [&lt;span&gt;1&lt;/span&gt;]. “Vancomycin flushing syndrome” often resolves by adjusting infusion velocity [&lt;span&gt;4-6&lt;/span&gt;]. Interestingly, both antibiotics induce mast-cell activation via the Mas-related G-protein coupled receptor-X2 (MRGPRX2) [&lt;span&gt;3-5&lt;/span&gt;]. In this study, we sought to evaluate whether patients with confirmed hypersensitivity to these ligands presented variants of the MRGPRX2 gene, and to assess these polymorphisms' functional implications.&lt;/p&gt;&lt;p&gt;From 2018 to 2019, in 3 centres in Spain, we prospectively recruited patients who suffered reactions clinically compatible with IHDRs, occurring within 1 h of receiving quinolones or vancomycin. Four to 8 months (mean: 16.6 [SD ± 14.8] weeks) after the index reaction, skin tests with these drugs were performed using standardized dilutions. Patients with a history of chronic urticaria and/or NSAID hypersensitivity, and, –to avoid including potentially IgE-mediated cases– those showing positive skin tests, were excluded. Provocation tests with the suspected culprit and alternatives were conducted when risk assessment did not contraindicate them. All index reactions were confirmed by a clinician at either the time of occurrence or during provocation. Twelve patients (median age: 49.5 [IQR 44.0–61.5] years, 66.6% females) finally participated and signed their informed consent.&lt;/p&gt;&lt;p&gt;Whole exome sequencing was performed using blood samples from patients after genomic DNA isolation and processing, and variables located in exonic and intronic splice site-flanking regions of the MRGPRX2 gene were assessed and filtered. Two non-synonymous, exonic variants of the gene were found in patients with quinolone hypersensitivity: Asn16His (N16H) (20% of patients, 10% of total alleles affected) and Asn62Ser (N62S) (40% of patients, 30% of alleles affected). A Ser313Arg (S313R) variant was detected in heterozygosis in one of the vancomycin-reactive patients, and N62S was detected in the other, affecting both alleles.&lt;/p&gt;&lt;p&gt;To test their functional effects, wild-type (WT) MRGPRX2 and MRGPRX2 carrying these three SNPs were transiently transfected in HEK293LTV cells (Cell Biolabs Inc., San Diego, CA, USA). Activation responses after incubation with different stimuli (substance P (SP), cortistatin-14, quinolones, and vancomycin) were measured using calcium and inositol-phosphate 1 (IP1) read-outs. Variants N16H and N62S, found together in 20% of quinolone hypersensitivity cases, were tested as “double-mutants”, as well as separate","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 9","pages":"873-876"},"PeriodicalIF":5.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cea.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979290","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":"Financial Ties of Paediatric Allergy and Immunology Professional Associations With the Formula Milk Industry: A Global Cross-Sectional Study","authors":"Katarzyna Henke-Ciążyńska,&nbsp;Daniel Pankowski,&nbsp;Daniel Munblit,&nbsp;Alice Fabbri,&nbsp;Quinn Grundy,&nbsp;Lisa Bero,&nbsp;Bartosz Helfer","doi":"10.1111/cea.70064","DOIUrl":"10.1111/cea.70064","url":null,"abstract":"","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 9","pages":"834-836"},"PeriodicalIF":5.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ara h 2105-124-Specific TH2A Cells Drive Peanut Allergy in DRB1*15:01 Individuals: A Detailed Epitope Analysis","authors":"Rebecca A. Gomez,&nbsp;Jue Hou,&nbsp;Vivian H. Gersuk,&nbsp;I-Ting Chow,&nbsp;Mary L. Farrington,&nbsp;David Robinson,&nbsp;William W. Kwok","doi":"10.1111/cea.70072","DOIUrl":"10.1111/cea.70072","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The IgE-mediated CD4 T-cell response to peanut (<i>Arachis hypogaea</i>) is heterogeneous, yet TH2 cells remain central drivers of pathology. This study aimed to dissect this complexity at the epitope level by focusing on the HLA-DRB1*15:01–DRB5*01:01 haplotype. Specifically, we examined how distinct epitope-specific T-cell subsets shape the immunological landscape of peanut allergy in peanut-allergic (PA) versus non-peanut-allergic (NPA) individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using in vitro and ex vivo MHC-II tetramer approaches, the phenotype, frequency, function, and transcriptome of CD4 T-cell responses to novel Ara h epitopes were assessed. Bulk RNA sequencing further characterised these T cells, allowing identification of subsets associated with TH2 polarisation in PA individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eleven HLA-DRB1*15:01 and DRB5*01:01-restricted epitopes were identified in Ara h 1, 2, 3, 6, 7, and 8 using tetramer-guided epitope mapping on cell lines, followed by ex vivo validation in peripheral blood. T-cell phenotype was epitope-dependent, with a distinct TH2A population specific to the epitope Ara h 2_105–124 (Ara h 2 p14) detected only in PA donors. These TH2A cells were phenotypically and transcriptionally distinct, marked by high CRTH2/CD161, low CD27, IL-5 production, and gene enrichment in cytokine signalling and lipid metabolism. Other epitope-specific T-cell subsets displayed more heterogeneous gene profiles related to immune activation, differentiation, and antigen presentation, underscoring the complexity of peanut-specific responses even within a single HLA haplotype.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings reveal that the strong TH2 bias in DRB1*15:01-DRB5*01:01 PA individuals arises from a distinct subset of Ara h 2 p14-specific TH2A cells characterised by a specialised metabolic and cytokine signalling program. At the same time, the functional diversity observed in non-Ara h 2 p14 subsets highlights the potential for leveraging these populations in tolerance-promoting therapies. Understanding the epitope-level heterogeneity of peanut-specific T-cells provides insight into the epitope-specific mechanisms driving peanut allergy and has potential implications for therapeutic interventions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 9","pages":"820-833"},"PeriodicalIF":5.2,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cea.70072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977457","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":"Changes in Childhood Atopic Dermatitis Incidence and Risk Factors Over Time: Results From Two German Birth Cohorts","authors":"Zhuoxin Peng,&nbsp;Linda P. Siziba,&nbsp;Hermann Brenner,&nbsp;Deborah Wernecke,&nbsp;Dietrich Rothenbacher,&nbsp;Jon Genuneit","doi":"10.1111/cea.70066","DOIUrl":"10.1111/cea.70066","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Atopic dermatitis (AD) is a common allergic skin disease. We aimed to assess the secular changes in the cumulative incidence of childhood AD and its risk factors over a decade.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used data from two methodologically similar cohort studies in Ulm, Germany, the Ulm Birth Cohort Study (UBCS, recruited in 2000/2001) and the Ulm SPATZ Health Study (recruited in 2012/2013). The cumulative incidences of AD as reported by their family physicians and parents up to the age of 4 years were compared by log-rank test across the two cohorts, using propensity score–based weighting to control confounders. We fitted multivariable Cox regression models to estimate hazard ratios and 95% confidence intervals (CIs) for the factors associated with the occurrence of physician- and parent-reported AD and compared the results between the two cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The 4-year cumulative incidence (95% confidence interval) of physician-reported AD (27.4% (24.4%–30.5%) in UBCS [2000/2001] vs. 26.4% (22.8%–30.2%) in SPATZ [2012/2013], <i>p</i> = 0.728) and parent-reported AD (14.5% (12.2%–17.0%) in UBCS [2000/2001] vs. 16.7% (14.0%–19.7%) in SPATZ [2012/2013], <i>p</i> = 0.211) remained stable between the two cohorts after propensity score–based weighting. We observed the changes in the association between AD and certain risk factors (e.g., family history of AD and infantile antibiotic use) over the decade, but the results need to be interpreted with caution due to the limited sample size, relatively high attrition rate and demographic differences between the two cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Over the decade, childhood AD incidence remained stable. Further studies are needed to verify whether there is a growing importance of environmental and microbiota-related factors for AD development over time.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 6","pages":"469-480"},"PeriodicalIF":6.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cea.70066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975360","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}