Allergology International最新文献

{"title":"Undressing DReSS as p-i mediated disease.","authors":"Werner J Pichler, Lester Thoo, Daniel Yerly, Tim Peyer, Oliver Hausmann, Yannick Muller, Marianne Lerch, Lukas Joerg, Thomas Harr, Katja Martin","doi":"10.1016/j.alit.2025.08.003","DOIUrl":"https://doi.org/10.1016/j.alit.2025.08.003","url":null,"abstract":"<p><p>Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS) is a severe T cell-mediated hypersensitivity reaction. T cells in DReSS are stimulated via the p-i mechanism (pharmacological interaction with immune receptors), where the drug shows an off-target binding to immune receptors (TCR and/or HLA) leading to an unorthodox activation of T cells. P-i stimulations are particularly strong in DReSS, as the causative drugs are typically administered at high doses for prolonged durations (>7 days) and bind with relatively high affinity to a specific HLA allele and/or TCR. This mechanism results in delayed yet profound immune activation, progressing through four distinct phases. The p-i concept provides a unifying explanation for many puzzling aspects of DReSS and has significant implications for diagnosis, management, and prevention. Recognizing drug concentration, therapy duration, and HLA affinity as key determinants of strong p-i-mediated immune activation can improve risk assessment, early diagnosis, and intervention strategies for DReSS.</p>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145309667","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":"Long-term efficacy and safety of dupilumab with concomitant topical corticosteroids in Japanese pediatric patients with moderate-to-severe atopic dermatitis: Results from a phase 3 open-label extension study.","authors":"Yoko Kataoka, Motohiro Ebisawa, Akio Tanaka, Mizuho Nagao, Elizabeth Laws, Hisakatsu Nawata, Kazuhiko Arima, Daisuke Watanabe, Xin Lu, Jennifer Maloney, Ariane Dubost-Brama, Ashish Bansal, Kenji Yahata","doi":"10.1016/j.alit.2025.09.002","DOIUrl":"https://doi.org/10.1016/j.alit.2025.09.002","url":null,"abstract":"<p><strong>Background: </strong>Dupilumab is approved in Japan for the treatment of atopic dermatitis in patients aged 6 months to 18 years. However, long-term data are lacking in this patient population. Here we report the final analysis of a long-term open-label extension (OLE) of a phase 3 study that assessed dupilumab in Japanese patients aged ≥6 months to <18 years with moderate-to-severe atopic dermatitis inadequately controlled with existing therapies.</p><p><strong>Methods: </strong>Study participants were randomly assigned to dupilumab or placebo with concomitant topical corticosteroids for 16 weeks, then to open-label dupilumab until approval or for 3 years, whichever came first.</p><p><strong>Results: </strong>Of the 62 participants randomized, 60 entered the OLE and continued to receive dupilumab (n = 28) or initiated dupilumab (n = 32). Improvements in clinical severity scores seen with dupilumab at Week 16 persisted up to Week 116, as confirmed by several efficacy endpoints (proportion of patients who achieved ≥75 % or ≥90 % improvement in Eczema Area and Severity Index [EASI] score, and Investigator's Global Assessment score of 0/1, and percent change in EASI scores from baseline). During the dupilumab exposure period, 93.5 % of patients experienced a treatment-emergent adverse event (TEAE). No adverse events leading to death, or TEAEs leading to study treatment discontinuation were observed during the OLE period. One (3.1 %) treatment-emergent positive anti-drug antibody response was observed during the OLE period in the placebo/dupilumab group.</p><p><strong>Conclusions: </strong>This analysis supports the long-term efficacy and safety of dupilumab in Japanese patients aged ≥6 months to <18 years with moderate-to-severe atopic dermatitis.</p>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145309670","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":"Association of allergen signatures with individualized allergic phenotypes.","authors":"Dachan Kim, Hyung-Ju Cho, Chang-Hoon Kim, Min-Seok Rha","doi":"10.1016/j.alit.2025.09.003","DOIUrl":"https://doi.org/10.1016/j.alit.2025.09.003","url":null,"abstract":"<p><strong>Background: </strong>Allergen sensitization patterns are heterogeneous, and their clinical relevance is often obscured by extensive cross-reactivity. We applied non-negative matrix factorization (NMF) to disentangle overlapping immunoglobulin E (IgE) signals and define clinically meaningful allergen signatures in a large Korean cohort.</p><p><strong>Methods: </strong>We analyzed 45,065 patients who underwent multiplex allergen testing (35 inhalants and food components) between 2010 and 2025. Class-scaled specific IgE values (0-6) were factorized by NMF (k = 4). Signature weights were related to asthma, allergic rhinitis, and atopic dermatitis using multivariable logistic regression and to peripheral eosinophil counts and total IgE using age- and sex-adjusted linear models.</p><p><strong>Results: </strong>Four signatures-mite, grass/weed, pet, and tree-explained 77.7 % of the variance in sensitization. The mite signature predominated (57.6 % of patients) and was strongly associated with allergic rhinitis (adjusted OR: 7.21, 95 % CI: 5.66-9.16), as well as marked increases in eosinophils and total IgE. The pet signature was the strongest predictor of asthma (OR: 8.90, 6.48-12.24). The tree signature showed the strongest association with atopic dermatitis (OR: 6.27, 3.81-10.32) and broader multisystem allergic morbidity. The grass/weed signature exhibited a biphasic age trajectory with a late-adult resurgence but had modest clinical impact. All signatures were significant and graded as determinants of blood eosinophil counts and IgE levels.</p><p><strong>Conclusions: </strong>Data-driven factorization of multiplex IgE panels yields portable allergen signatures that refine attribution of asthma, allergic rhinitis, and atopic dermatitis and link serologic patterns to systemic inflammation.</p>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145309720","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":"The Cyto-LTT: A multiplex cytokine assay to detect and assess the strength of T cell reactivity in drug hypersensitivity.","authors":"Tim Peyer, Lester Thoo, Daniel Yerly, Oliver Hausmann, Lukas Joerg, Werner J Pichler","doi":"10.1016/j.alit.2025.09.004","DOIUrl":"https://doi.org/10.1016/j.alit.2025.09.004","url":null,"abstract":"<p><strong>Background: </strong>The conventional in vitro lymphocyte transformation test (LTT) for diagnosing drug hypersensitivity reactions (DHRs) is limited by low sensitivity. To improve detection and assess T cell activation strength, we adapted this test to a cytokine-based assay (Cyto-LTT) by measuring IL-5, IL-13, IFN-γ, granzyme B and granulysin secretion.</p><p><strong>Methods: </strong>We retrospectively analyzed 851 positive Cyto-LTT results (from a total 6058 Cyto-LTT) from a Swiss drug hypersensitivity diagnostic laboratory's database, including 97 patients with Drug Rash with Eosinophilia and Systemic Symptoms (DReSS) and 754 patients with exanthems, including urticarial, maculo- and maculopapular-rash. Cytokine responses measured across three drug concentrations of amoxicillin (n = 734), aromatic sulfonamides (n = 81), or vancomycin (n = 36) were evaluated for dose-dependency and the correlation to the clinical manifestations. A grading system defined strong responses as cytokine stimulation indices (SI) above the 75th percentile (per cytokine) in the exanthem group which served as a comparator for the DReSS cases.</p><p><strong>Results: </strong>Cytokine responses increased dose-dependently. DReSS cases exhibited significantly stronger cytokine secretions compared to exanthem cases (p < 0.001), with strong responses observed in 62.9 % of DReSS patients versus 33.6 % of exanthem cases.</p><p><strong>Conclusions: </strong>Cyto-LTT reveals dose-dependent T cell activation in delayed drug hypersensitivity reactions, challenging the notion that drug allergic reactions are dose-independent. The assay not only identifies the culprit drug but also quantifies immune activation strength. Stronger responses were more frequent in DReSS, suggesting the test may also inform risk assessment-particularly in guiding caution with structurally related compounds or in patients at risk for severe or recurrent reactions.</p>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145303979","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":"YTHDF1 regulates the proliferation and differentiation of keratinocytes via the PI3K/AKT signaling pathway in atopic dermatitis","authors":"Maoxin Huang ,&nbsp;Liping Dong ,&nbsp;Yue He ,&nbsp;Xinying Cai ,&nbsp;Yun Lu ,&nbsp;Jinlei Xu ,&nbsp;Fengli Xiao","doi":"10.1016/j.alit.2025.04.005","DOIUrl":"10.1016/j.alit.2025.04.005","url":null,"abstract":"<div><h3>Background</h3><div>YTHDF1, a critical regulator of cellular processes, has attracted attention for its involvement in some inflammatory diseases. However, its specific association with atopic dermatitis (AD) remains unclear. The objective is to investigate the functional roles and underlying mechanisms of YTHDF1 in AD.</div></div><div><h3>Methods</h3><div>The expression of YTHDF1 was investigated by bioinformatics analysis and skin lesions of AD patients. The functional role and upstream and downstream regulatory mechanisms of YTHDF1 were examined through a series of <em>in vitro</em> and <em>in vivo</em> experiments. Adeno-associated virus (AAV)-mediated delivery of YTHDF1 in the AD mouse model was evaluated for its therapeutic potential.</div></div><div><h3>Results</h3><div>Bioinformatics analysis revealed that the <em>YTHDF1</em> mRNA level in the skin lesions of AD was significantly higher than that in healthy people. YTHDF1 expression was significantly elevated in AD skin lesions, the DNCB-induced AD mouse model, and primary human keratinocytes and HaCaT cells stimulated with interleukin (IL)-4/IL-13, compared to controls. Both <em>in vitro</em> and <em>in vivo</em> experiments revealed that upregulation of YTHDF1 in AD exacerbated cell proliferation and inhibited keratinization by activating the PI3K/AKT pathway, which was modulated via the IL-4/IL-13/STAT3 axis. Moreover, topical application of AAV-YTHDF1 significantly improved AD-like lesions in the mouse model.</div></div><div><h3>Conclusions</h3><div>This study identifies YTHDF1 as a contributor to AD pathogenesis by influencing keratinocyte proliferation and differentiation. It also suggests that YTHDF1 could be a potential therapeutic target for AD treatment.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 4","pages":"Pages 591-604"},"PeriodicalIF":6.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250394","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":"Factors associated with egg aversion after a negative oral food challenge result in children with egg allergies: A multicenter questionnaire survey in Japan","authors":"Naoko Fusayasu ,&nbsp;Tomoyuki Asaumi ,&nbsp;Ken-Ichi Nagakura ,&nbsp;Kyohei Takahashi ,&nbsp;Noriyuki Yanagida ,&nbsp;Sakura Sato ,&nbsp;Shigehito Emura ,&nbsp;Akiko Murano ,&nbsp;Hisashi Konno ,&nbsp;Yasuko Shibukawa ,&nbsp;Makoto Suzuki ,&nbsp;Motohiro Ebisawa","doi":"10.1016/j.alit.2025.05.005","DOIUrl":"10.1016/j.alit.2025.05.005","url":null,"abstract":"<div><h3>Background</h3><div>Many children with egg allergies experience aversion, which hinders reintroduction after a negative oral food challenge (OFC). We aimed to assess factors associated with egg aversion in children after negative egg OFCs.</div></div><div><h3>Methods</h3><div>We conducted a multicenter questionnaire survey between January and December 2018 and retrospectively collected background data from the medical records. Children aged 3–18 years with a history of an immediate reaction to eggs more than 6 months after a negative OFC to half of a heated whole egg were included. We defined “aversion” as a dislike of eating eggs or processed egg products.</div></div><div><h3>Results</h3><div>We included 140 children (median age: 6.7 years) who passed OFCs at the median age of 3.3 years and had a median specific-IgE (sIgE) to egg white of 10.0 kU_A/L. Overall, 57 (41 %) children had an egg aversion. “Disliking the food texture or taste” (61 %) was the most frequent reason for an aversion. The associated factor in the multivariate analysis was older age during a negative OFC (adjusted odds ratio: 1.24, 95 % confidence interval: 1.04–1.49). The aversion frequency depended on the type of cooking methods, where 68 % had an aversion to boiled egg whites, and less than 5 % had an aversion to egg-containing deep-fried chicken.</div></div><div><h3>Conclusions</h3><div>About half of the children after negative OFC had an egg aversion, and it was associated with older age during negative OFC. Careful follow-up and guidance with consideration of less aversive cooking methods are important in older age groups.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 4","pages":"Pages 616-621"},"PeriodicalIF":6.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295166","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":"Black-box optimization in immunology and beyond: A practical guide to algorithms and future directions","authors":"Takanori Kawabata ,&nbsp;Taku Tsuzuki ,&nbsp;Tsuyoshi Tatsukawa ,&nbsp;Kota Matsui ,&nbsp;Eiryo Kawakami","doi":"10.1016/j.alit.2025.08.006","DOIUrl":"10.1016/j.alit.2025.08.006","url":null,"abstract":"<div><div>The immune system presents some of the most complex challenges in biology, encompassing nonlinear interactions, high-dimensional regulatory mechanisms, and substantial variability across individuals and contexts. As a result, traditional model-driven approaches often fall short in optimizing experimental conditions or therapeutic strategies. Black-box optimization methods—particularly Bayesian optimization (BO) and evolutionary algorithms (EAs)—offer powerful tools for guiding biological discovery when mechanistic understanding is incomplete or intractable. These algorithms iteratively propose informative experiments by learning from noisy, expensive, and sparse data, enabling efficient exploration of vast experimental spaces. In this review, we provide a comprehensive overview of black-box optimization methodologies and their applications in life science, with a particular focus on immunology and allergy research. We detail how black-box optimization is transforming various stages of biomedical R&amp;D, from molecular design (e.g., antibodies, peptides) and gene circuit tuning to culture protocol optimization and patient-specific dose adjustment. We highlight key algorithmic advances, including constrained, multi-objective, parallel and high-dimensional BO, as well as recent developments such as grey-box optimization and transfer learning. Practical considerations, such as software tools and reproducibility-enhancing checklists, are also discussed. By integrating black-box optimization with automated experimentation platforms and high-throughput biological systems, researchers can accelerate discovery, personalize interventions, and systematically optimize complex immunological processes. We argue that black-box optimization will become a foundational component of experimental design and decision-making in the life sciences, bridging computational strategies with biological insight in increasingly adaptive and interpretable ways.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 4","pages":"Pages 549-562"},"PeriodicalIF":6.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132189","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":"Artificial intelligence and big data: Reshaping allergy research and patient care","authors":"Eiryo Kawakami (Guest Editor, Allergology International)","doi":"10.1016/j.alit.2025.09.001","DOIUrl":"10.1016/j.alit.2025.09.001","url":null,"abstract":"","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 4","pages":"Pages 497-498"},"PeriodicalIF":6.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236463","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":"The role of GATA2 in the expression of the soluble decoy receptor ST2/IL1RL1 in human and mouse mast cells","authors":"Kazuki Nagata ,&nbsp;Kazumi Kasakura ,&nbsp;Kenta Ishii ,&nbsp;Naoto Ito ,&nbsp;Mutsuko Hara ,&nbsp;Nobuhiro Nakano ,&nbsp;Ko Okumura ,&nbsp;Chiharu Nishiyama","doi":"10.1016/j.alit.2025.04.004","DOIUrl":"10.1016/j.alit.2025.04.004","url":null,"abstract":"","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 4","pages":"Pages 637-640"},"PeriodicalIF":6.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133345","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":"Convergent monoclonal IgE antibodies from peanut allergic patients are multispecific to immunodominant epitopes of unrelated major peanut and tree nut allergens","authors":"Stefan Kabasser ,&nbsp;Tanja Kalic Kamath ,&nbsp;Ernst Eber ,&nbsp;Aleksandra Podzhilkova ,&nbsp;Christian Lupinek ,&nbsp;Wolfgang Hemmer ,&nbsp;Mugdim Bublin ,&nbsp;Derek Croote ,&nbsp;Soheila J. Maleki ,&nbsp;Heimo Breiteneder ,&nbsp;Karin Hoffmann-Sommergruber ,&nbsp;Christian Radauer ,&nbsp;Merima Bublin","doi":"10.1016/j.alit.2025.05.007","DOIUrl":"10.1016/j.alit.2025.05.007","url":null,"abstract":"<div><h3>Background</h3><div>Convergent selection has been identified in the IgE antibody repertoires of peanut-allergic individuals, primarily targeting the 2S albumin Ara h 2 and cross-reacting with two other major allergens, the vicilin Ara h 1 and the legumin Ara h 3. In this study, we aimed to investigate the structural and functional basis of this cross-reactivity and its contribution to the co-sensitization to tree nuts often observed in peanut-allergic subjects.</div></div><div><h3>Methods</h3><div>Six convergent antibodies, targeting the immunodominant Ara h 2-DPYSPS motif-associated sequence, and their reverted germline version, were produced as human IgG1 and IgE. Antibody specificity to natural and recombinant peanut and tree nut allergens and allergen-derived peptides was evaluated using ELISA, immunoblotting, inhibition tests, and basophil activation assays.</div></div><div><h3>Results</h3><div>The six antibodies showed reactivity to Ara h 1, Ara h 2, Ara h 3 and weak reactivity to tree nut legumins, especially from almond, walnut and Brazil nut. The germline antibody exclusively recognized Ara h 2. Basophils sensitized with the individual antibodies were activated by Ara h 2 at a concentration of 10 ng/ml and at 100-fold higher concentrations by Ara h 1 and Ara h 3, but not by tree nut legumins. The three Ara h 1- and two Ara h 3-derived antibody-binding peptides, with one from each group previously identified as immunodominant, are in close proximity and may contribute to conformational epitopes.</div></div><div><h3>Conclusion</h3><div>The biological activity of affinity-matured cross-reactive antibodies with Ara h 2-associated sequence convergence may explain the high allergenic potency of peanut and clinically irrelevant co-sensitizations to tree nuts commonly observed in peanut-allergic patients.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 4","pages":"Pages 622-632"},"PeriodicalIF":6.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486739","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}