Allergy最新文献

{"title":"Allergic Reactivity and Memory Occur Independently of Sequential Switching Through IgG1.","authors":"Joshua F E Koenig, Adam K Wade-Vallance, Rodrigo Jiménez-Saiz, Kelly Bruton, Siyon Gadkar, Emily Grydziuszko, Tina D Walker, Melissa E Gordon, Amy E Gillgrass, Justin J Taylor, Susan Waserman, Manel Jordana","doi":"10.1111/all.16460","DOIUrl":"https://doi.org/10.1111/all.16460","url":null,"abstract":"<p><p>Allergic reactions to foods are primarily driven by allergen-binding immunoglobulin (Ig)E antibodies. IgE-expressing cells can be generated through direct switching from IgM to IgE or a sequential class switching pathway where activated B cells first switch to an intermediary isotype, most frequently IgG1, and then to IgE. It has been proposed that sequential class switch recombination is involved in augmenting the severity of allergic reactions, generating high affinity IgE, differentiation of IgE plasma cells, and in holding the memory of IgE responses. We directly tested these possibilities by comparing the allergic immunity of wild-type and IgG1-deficient (hMT) mice. We found that sequential switching through IgG1 was not required to maintain the binding capacity of IgE nor for its ability to promote degranulation and elicit anaphylaxis against bona fide food allergens. Furthermore, the absence of sequential switching modestly impacted IgE affinity and clinical reactivity against hapten antigens, suggesting that the nature of the antigen impacts the requirement for sequential switching. At a cellular level, the capacity to undergo sequential switching through IgG1 provided no competitive advantage for subsequent IgE expression among germinal center B cells or plasma cells. Furthermore, the recall of allergic immunity at memory timepoints was preserved in the absence of sequential switching through IgG1, a finding that corresponded with intact type 2 memory B cell polarization. Together, these data demonstrate that sequential switching through IgG1 is redundant in sensitization, anaphylaxis, and the persistence of allergy, ultimately revealing that IgE derived from any switching source should be targeted by novel therapeutics seeking to ameliorate allergic diseases.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Intestinal Permeability Using Serum Biomarkers in Learning Early About Peanut Allergy Trial.","authors":"Ozge Nur Aktas, Allyson Mateja, Min Jenny Li, Lindsay Chatman, Megan C Grieco, Carolyn H Baloh, Michelle Huffaker, Lisa M Wheatley, George du Toit, Gideon Lack, Erica Brittain, Pamela A Frischmeyer-Guerrerio","doi":"10.1111/all.16464","DOIUrl":"https://doi.org/10.1111/all.16464","url":null,"abstract":"<p><strong>Background: </strong>Intestinal barrier dysfunction may lead to a break in tolerance and development of food allergy (FA). There is contradictory evidence on whether intestinal permeability (IP) is altered in IgE-mediated FA. Thus, we sought to determine whether IP differed between children with eczema who did (FA group) or did not (atopic controls, ACs) develop FA and whether peanut sensitization, allergy, and early introduction impacted IP using serum biomarkers zonulin, soluble CD14, and Intestinal Fatty Acid Binding Protein among randomly selected participants enrolled in the Learning Early About Peanut allergy trial.</p><p><strong>Methods: </strong>FA group was defined as having at least one FA at either baseline (4-11 months) or 60 months of age (V60). ACs had eczema at baseline and no FA at either visit. Serum IP markers (sIPMs) were measured by ELISA at baseline and V60, and their relationship with the clinical characteristics of participants was analyzed using parametric tests and linear regression models.</p><p><strong>Results: </strong>We evaluated 237 FA subjects and 76 ACs. sIPM levels were similar in FA subjects and ACs at baseline and V60. Age when the child first developed any FA (< 1 year vs. > 1 year), eczema severity, peanut sensitization, peanut allergy, and early peanut introduction were not statistically significantly associated with sIPM levels. Total IgE and eosinophil levels, peanut-specific IgE, IgG4, and IgG4/IgE ratio were not correlated with sIPM levels.</p><p><strong>Conclusions: </strong>No differences in sIPMs were detected to support altered IP in infants with FA compared to ACs or following early peanut introduction among peanut-sensitized children.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 2 IgG Memory B Cells as Precursors of IgE Plasma Cells","authors":"Larissa Nogueira de Almeida,&nbsp;Janina Petry,&nbsp;Christopher C. Udoye","doi":"10.1111/all.16473","DOIUrl":"10.1111/all.16473","url":null,"abstract":"&lt;p&gt;Immunoglobulin E (IgE) is a major mediator of allergic reactions and can activate mast cells and basophils via the high-affinity IgE receptor. Some IgE-mediated allergies can last a lifetime, but IgE-secreting plasma cells (PCs) and IgE+ memory B cells (MBCs) are rare, leading to questions about the origin of allergen-specific IgE antibodies (Abs). In recent years, studies have suggested that allergen-specific B cell memory is predominantly held by IgG(1) MBCs, which can become IgE-secreting PCs during a recall response [&lt;span&gt;1, 2&lt;/span&gt;]. A recent article by Koenig and colleagues proposed a novel class-switched MBC population with type 2 immune markers, which they termed MBC2, as a major progenitor of IgE PCs [&lt;span&gt;3&lt;/span&gt;]. The most important findings of their work are highlighted in Figure 1.&lt;/p&gt;&lt;p&gt;Using single-cell RNA sequencing (scRNA-seq), the authors identified 21 MBC clusters in both allergic and non-allergic subjects (Figure 1, upper panel). Two MBC clusters, collectively termed MBC2, expressed high levels of the low-affinity IgE receptor (CD23) and receptors for the type 2-associated cytokines IL-4 (IL4R) and IL-13 (IL13RA1). MBC2s contained two subsets, &lt;i&gt;IGHE&lt;/i&gt;+ and &lt;i&gt;IGHE&lt;/i&gt;- MBC2s, which differed in the expression of IgE germline transcripts (εGLTs), but barely expressed productively rearranged IgE transcripts. Instead, both subsets expressed predominantly IgG1 B cell receptors (BCRs), and a relatively high proportion of IgG4 in the &lt;i&gt;IGHE&lt;/i&gt;+ MBC2s. Importantly, the frequency of &lt;i&gt;IGHE+&lt;/i&gt; MBC2 cells was independent of the allergic status and did not correlate with allergic disease. The authors confirmed this MBC2 phenotype at the protein level with additional elevated expression of CD40 and HLA-DR/DQ genes and a unique down-regulation of the inhibitory IgG receptor FcγRIIB compared to other MBC subsets.&lt;/p&gt;&lt;p&gt;The authors also found a similar IL-4-dependent CD23hi/IL-4Rαhi MBC2-like population in mice, which emerged in the context of type 2 but not type 1 sensitization, with 2% of antigen-specific, class-switched MBCs showing the &lt;i&gt;IGHE+&lt;/i&gt; MBC2 phenotype (the majority of which expressed an IgG1 BCR) upon type 2 sensitization. Importantly, the authors also showed that antigen-specific MBC2 generation in mice was primarily dependent on germinal center (GC) reactions, with less than 10% of antigen-specific MBC2s appearing to develop independently of GCs.&lt;/p&gt;&lt;p&gt;Finally, an analysis of birch allergic patients undergoing sublingual immunotherapy (SLIT) revealed a clonal connection between IgE-producing PCs analyzed 1 month after the start of SLIT and MBC2s analyzed before or 1 month after the start of SLIT, although it remained unclear what percentage of IgE+ PC clones were found in MBC2 clones (Figure 1, lower panel). Together with an independent article in the same issue [&lt;span&gt;4&lt;/span&gt;], Koenig and colleagues provide insights into allergen-specific B cell memory by identifying class-switched &lt;i&gt;IGHE&lt;/i&gt;+ MBC2s with ","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 3","pages":"908-910"},"PeriodicalIF":12.6,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16473","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Puberty and Risk of Asthma: Meta‐Analysis and Systematic Review","authors":"Fu‐Min Chang, Yung‐Feng Lin, Hsiao‐Chi Chuang, Jhih‐Wei Hsu, Yang‐Ching Chen","doi":"10.1111/all.16471","DOIUrl":"https://doi.org/10.1111/all.16471","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"49 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-Life Diet and Persistent Atopic Dermatitis: A Nationwide Cohort Study.","authors":"Ji Su Lee, Seong Rae Kim, Dong Hyo Kim, Soo Ick Cho, Dong Hun Lee","doi":"10.1111/all.16469","DOIUrl":"https://doi.org/10.1111/all.16469","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CT‐P39 Compared With Reference Omalizumab in Chronic Spontaneous Urticaria: Results From a Double‐Blind, Randomized, Active‐Controlled, Phase 3 Study","authors":"Sarbjit S. Saini, Marcus Maurer, Yevgeniya Dytyatkovska, Ewa Springer, Maria Ratkova, Borislava Krusheva, Chun Wook Park, Grazyna Pulka, Marta Chełmińska, Adam Reich, Sunghyun Kim, Keumyoung Ahn, Suyoung Kim, Sewon Lee, Jieun Ka, Jongho Kim, Clive Grattan","doi":"10.1111/all.16446","DOIUrl":"https://doi.org/10.1111/all.16446","url":null,"abstract":"BackgroundThis study compared the therapeutic equivalence of CT‐P39 (an omalizumab biosimilar) and EU‐approved reference omalizumab (ref‐OMA) in patients with chronic spontaneous urticaria.MethodsThis double‐blind, randomized, active‐controlled Phase 3 study (NCT04426890) included two 12‐week treatment periods (TPs). In TP1, patients received CT‐P39 300 mg, ref‐OMA 300 mg, CT‐P39 150 mg, or ref‐OMA 150 mg. In TP2, patients treated with ref‐OMA 300 mg were rerandomized to CT‐P39 300 mg or ref‐OMA 300 mg; patients initially randomized to CT‐P39 300 mg continued this regimen; and patients initially randomized to CT‐P39 or ref‐OMA 150 mg received 300 mg dosing with the same drug. The primary endpoint for the assessment of therapeutic equivalence of CT‐P39 300 mg and ref‐OMA 300 mg was change from baseline in weekly itch severity score (ISS7) at week 12.ResultsIn TP1, 619 patients were randomized (CT‐P39 300 mg, <jats:italic>n</jats:italic> = 204; ref‐OMA 300 mg, <jats:italic>n</jats:italic> = 205; CT‐P39 150 mg, <jats:italic>n</jats:italic> = 107; ref‐OMA 150 mg, <jats:italic>n</jats:italic> = 103). Equivalence was demonstrated between CT‐P39 300 mg and ref‐OMA 300 mg for mean change from baseline in ISS7 at week 12; confidence intervals (CIs) were within predefined equivalence margins: global analysis: treatment difference 0.77, 95% CI –0.37 to 1.90; US analysis: treatment difference 0.70, 90% CI –0.22 to 1.63. The proportion of patients experiencing ≥ 1 treatment‐related adverse event was comparable across groups. Secondary efficacy, quality of life, pharmacokinetic, safety, and immunogenicity outcomes were comparable between groups at a given dose level, with no evident impact of switching.ConclusionsEquivalent efficacy was observed between CT‐P39 and ref‐OMA, with comparable safety also evident.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"127 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comorbid Bronchial Asthma, Atopic Dermatitis and Hashimoto's Thyroiditis Are Risk Factors for Early‐Onset, Severe and Prolonged Alopecia Areata","authors":"Annika Friedrich, Marie‐Therese Schmitz, Yasmina Gossmann, Silke Redler, Bettina Blaumeiser, Gerhard Lutz, Ulrike Blume‐Peytavi, Markus M. Nöthen, Regina C. Betz, F. Buket Basmanav","doi":"10.1111/all.16468","DOIUrl":"https://doi.org/10.1111/all.16468","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"36 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Algorithms in Allergy: Organ‐Specific Allergen Challenges for the Phenotyping of Chronic Respiratory Diseases","authors":"Dulce Sanchez‐Torralvo, Almudena Testera‐Montes, Guillermo Bentabol‐Ramos, Ibon Eguiluz‐Gracia, Ralph Mösges, Maria J. Torres","doi":"10.1111/all.16470","DOIUrl":"https://doi.org/10.1111/all.16470","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"23 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skin Tape Stripping Reveals Distinct Biomarker Profiles in Chronic Hand Eczema of Patients With and Without Comorbid Atopic Dermatitis","authors":"Jonathan Bar, Ester Del Duca, Eden David, Swaroop Bose, Gabriella Chefitz, Patrick M. Brunner, Robert Bissonnette, Emma Guttman‐Yassky","doi":"10.1111/all.16466","DOIUrl":"https://doi.org/10.1111/all.16466","url":null,"abstract":"IntroductionChronic hand eczema (CHE) is a highly prevalent inflammatory skin condition which is often resistant to conventional treatments. Molecular insights of CHE remain limited. Tape stripping combined with high‐throughput RNA sequencing can now provide a better insight into CHE pathogenesis in a minimally invasive fashion.MethodsWe collected tape strip samples from lesional and non‐lesional skin of 66 patients with moderate‐to‐severe CHE, comprising 33 with and 33 without comorbid atopic dermatitis (AD), and performed bulk RNA sequencing. Results were compared to tape strips from palmar skin of age/race/sex‐matched healthy controls (HC). Differentially expressed genes (DEGs) (fold change/FCH &gt; 1.5 and false discovery rate/FDR &lt; 0.05) were calculated and correlated with clinical severity scores including hand eczema severity index (HECSI) and modified total lesion symptoms score (mTLSS).ResultsTape strip isolates detected a common phenotype in CHE lesions regardless of AD status, including upregulated type‐1 (<jats:italic>IL12RB2</jats:italic>, <jats:italic>IFNGR1</jats:italic>, <jats:italic>IFNGR2</jats:italic>, <jats:italic>MX1</jats:italic>) and type‐2‐associated inflammatory mediators (<jats:italic>CCL22</jats:italic>, <jats:italic>CCL24</jats:italic>, OX40/<jats:italic>TNFRSF4</jats:italic>, TSLPR/<jats:italic>CRLF2</jats:italic>, <jats:italic>GATA3</jats:italic>), paralleled by downregulated epidermal barrier markers (i.e., <jats:italic>FLG</jats:italic> or <jats:italic>LORICRIN</jats:italic>). Non‐lesional skin demonstrated a similar, albeit milder, dysregulation pattern, with additional reduction in type‐17 pathways. Lesional skin of CHE patients without AD showed greater skewing towards type‐1 immunity (<jats:italic>IL15RA</jats:italic>, <jats:italic>CXCL9</jats:italic>), while CHE from AD patients showed a more pronounced type‐2 inflammatory pattern (<jats:italic>IL13</jats:italic>, <jats:italic>CCL17</jats:italic>) and their gene expression biomarkers had greater and more significant correlations with clinical severity markers.ConclusionTape stripping can capture detailed immune and skin barrier abnormalities in CHE and identify potential novel subtype‐specific treatment targets. Stronger correlations in patients with AD suggest a more homogenous disease phenotype than in CHE non‐AD patients.Trial Registration: NCT03728504","PeriodicalId":122,"journal":{"name":"Allergy","volume":"12 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Impact of COVID-19 on Subcutaneous Immunotherapy Persistence and Efficacy in Allergic Rhinitis.","authors":"Xuan Yuan, Liyuan Liu, Benjian Zhang, Shaobing Xie, Lai Meng, Wei Zhong, Jiaxin Jia, Hua Zhang, Weihong Jiang, Zhihai Xie","doi":"10.1111/all.16467","DOIUrl":"https://doi.org/10.1111/all.16467","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}