Allergy最新文献

{"title":"Biomarkers for a less invasive strategy to predict children with eosinophilic esophagitis.","authors":"Helena Thulin, Ladan Mansouri, Maria Altman, Simon Kebede Merid, Joachim Lundahl, Caroline Nilsson, Jesper Säfholm","doi":"10.1111/all.16275","DOIUrl":"https://doi.org/10.1111/all.16275","url":null,"abstract":"<p><strong>Background: </strong>Noninvasive biomarkers for diagnosing and monitoring eosinophilic esophagitis (EoE) are currently lacking. This study evaluates 20 biomarkers in serum and saliva, aiming to assess their diagnostic potential in pediatric EoE patients and healthy individuals.</p><p><strong>Methods: </strong>Blood and saliva from children undergoing upper endoscopy were analyzed for biomarkers, including absolute eosinophil count (AEC), eosinophil-derived neurotoxin (EDN), total and specific IgG₄-antibodies (sIgG₄), specific IgE-antibodies (sIgE) and 15-hydroxyeicosatetraenoic acid (15(S)-HETE). Some patients participated twice, forming a longitudinal cohort. The ability to use the biomarkers to predict the EoE diagnosis was evaluated.</p><p><strong>Results: </strong>Analysis from 105 children divided into active EoE, remission, and healthy, revealed elevated levels of serum biomarkers (AEC, EDN, 15(S)-HETE, sIgG₄, and sIgE) in active EoE compared to healthy individuals. A combination of biomarkers (AEC, EDN, sIgE to egg white and wheat) and symptoms showed an AUC of 0.92 in distinguishing between the three groups. We further showed that optimal cutoff values for these biomarkers could discriminate between active EoE and healthy with a sensitivity of 88% and a specificity of 100% in distinguishing EoE (active and in remission) from healthy. Longitudinally, levels of EDN, sIgG₄ to Bos d 4, Bos d 5, Bos d 8, gliadin, and birch, and sIgE to milk decreased in patients progressing from active EoE to remission (p <.05).</p><p><strong>Conclusions: </strong>This study identified novel biomarkers associated with EoE and proposes a panel, together with symptoms, for effective discrimination between active EoE, EoE in remission, and healthy individuals. The findings may contribute to a less invasive diagnostic method and may be a potential surveillance tool for pediatric EoE patients.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141998927","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":"Indirect case-matched comparison of anti-IL4Rα versus anti-IL5Rα on airway hyperresponsiveness","authors":"Rory Chan,&nbsp;Kirsten Stewart,&nbsp;Chris RuiWen Kuo,&nbsp;Brian Lipworth","doi":"10.1111/all.16283","DOIUrl":"10.1111/all.16283","url":null,"abstract":"&lt;p&gt;The efficacy of biologics on airway hyperresponsiveness (AHR) has been studied before, but evidence is lacking in regard to which biologic is most effective.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Therefore, we performed a post-hoc case-matched analysis of two prospective single-arm open-label phase IV clinical trials investigating benralizumab (EudraCT2019-003763-22) and dupilumab (EudraCT2021-005593-25) on mannitol induced AHR in patients with uncontrolled type 2 high severe asthma. Twelve out of 21 patients from each study (&lt;i&gt;n&lt;/i&gt; = 24 total) were case matched according to baseline PD&lt;sub&gt;10&lt;/sub&gt; for appropriate comparison.&lt;/p&gt;&lt;p&gt;Patients taking benralizumab received a higher daily dose of inhaled corticosteroids but exhibited similar asthma control and lung function (Table 1). Dupilumab conferred greater improvements than benralizumab for mannitol PD&lt;sub&gt;10&lt;/sub&gt; as geometric mean fold change (95% CI) from baseline: Dupi 3.77(2.30,6.18) &lt;i&gt;p&lt;/i&gt; &lt; .001 versus Benra 1.81(1.09,3.01) &lt;i&gt;p&lt;/i&gt; &lt; .05, amounting to a between treatment doubling difference (95% CI) of 1.06(0.09,2.02) &lt;i&gt;p&lt;/i&gt; &lt; .05 (Figure 1A). There was also greater attenuation for mannitol response dose ratio (RDR) as geometric mean fold change: Dupi 6.11(2.98,12.50) &lt;i&gt;p&lt;/i&gt; &lt; .001 versus Benra 1.77(1.00,3.15) &lt;i&gt;p&lt;/i&gt; = .05 amounting to a between-treatment doubling difference 1.78(0.54,3.03) &lt;i&gt;p&lt;/i&gt; &lt; .01. Between baseline and week 12, there were no changes in fixed-dose ICS/LABA for patients taking benralizumab. In the same timeframe, the mean daily dose of extra fine BDP/FF 100/6 μg Nexthaler was reduced by 1.2 actuations using the dose counter, equating to a mean 240 μg budesonide equivalent reduction.&lt;/p&gt;&lt;p&gt;After 12 weeks the absolute geometric mean PD&lt;sub&gt;10&lt;/sub&gt; was higher with Dupi 542 mg (437,672) versus Benra 267 mg (158,449) amounting to a geometric mean fold (95%CI) difference 2.08(1.07,4.05) &lt;i&gt;p&lt;/i&gt; &lt; .05. Moreover, after 12 weeks there were proportionately more patients who exhibited AHR remission with Dupi versus Benra: &lt;i&gt;n&lt;/i&gt; = 8/12(67%) versus &lt;i&gt;n&lt;/i&gt; = 3/12(25%) &lt;i&gt;p&lt;/i&gt; &lt; .05 (Figure 1B).&lt;/p&gt;&lt;p&gt;This is the first indirect case-matched comparison of dupilumab versus benralizumab on mannitol AHR in uncontrolled type 2 high-severe asthma. There was greater AHR attenuation with dupilumab along with a higher likelihood for inducing AHR remission. Patients who achieved AHR remission, as PD&lt;sub&gt;10&lt;/sub&gt; ≥ 635 mg at 12 weeks, were censored at the maximum administered mannitol dose of 635 mg thereby underestimating the true extent of AHR improvement. Indeed, this degree of underestimation would have been amplified in terms of the relative doubling difference between treatments since more patients (67% vs. 25%) achieved AHR remission with dupilumab. Previously, some investigators have censored at twice the maximum dose of mannitol (1270 mg) to account for such underestimation.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; However, by the same token censoring at 1270 mg","PeriodicalId":122,"journal":{"name":"Allergy","volume":"79 10","pages":"2873-2875"},"PeriodicalIF":12.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16283","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994809","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":"Type 2 memory B cells: The repository of allergic memory?","authors":"Jesse Mulder,&nbsp;Alexandra R. Dvorscek,&nbsp;Zhoujie Ding","doi":"10.1111/all.16278","DOIUrl":"10.1111/all.16278","url":null,"abstract":"&lt;p&gt;Allergy is defined as an inappropriate immune response to a typically innocuous agent. Many allergic responses are IgE-mediated, wherein allergen-specific IgE antibodies bind mast cells and basophils to elicit degranulation upon allergen reexposure. Common allergens include proteins derived from foods (e.g., milks, peanuts), pollens (e.g., rye grass, birch), and insect-and arthropod-derived products (e.g., bee venom, house dust mite). Currently, disease-modifying treatments for allergies are limited, and a key obstacle to the development of novel therapies is an incomplete understanding of the etiology and maintenance of allergy, particularly how patients maintain sensitization for years between known exposures. Previous work has proposed that IgE memory resides within long-lived IgE antibody-secreting cells (ASC) or IgE memory B cells (MBC). A third explanation of IgE memory (Figure 1), investigated here by Ota, Hoehn, Fernandes-Braga and colleagues, supports that a subset of non-IgE B cells, specifically “type 2-marked” IgG MBC, are key for persistent sensitization, serving as a reservoir for allergic memory.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;In pediatric patients with peanut-allergy, Ota et al. found a population of IgG MBC that had upregulated &lt;i&gt;FCER2&lt;/i&gt; (encoding CD23) and &lt;i&gt;IL4R&lt;/i&gt; expression, marking them as type 2 cytokine-experienced cells. Consistent with a relationship to atopy, the frequency of CD23&lt;sup&gt;+&lt;/sup&gt; IgG MBC was highest in allergic patients with elevated peanut-specific IgE titers and correlated with total IgE titers. Moreover, in vitro stimulation of sorted IgG MBC from patients with high peanut-specific serum IgE revealed a greater incidence of peanut-specific antibodies in the supernatant of cultured CD23&lt;sup&gt;+&lt;/sup&gt; or IL-4R&lt;sup&gt;+&lt;/sup&gt; MBC compared to double negative counterparts (Figure 2). To further characterize the peanut-specific B cell compartment, the authors performed single cell analyses of B cells that bound Ara h 2 (one of two immunodominant allergens in peanut) or a control antigen, diphtheria toxin (DT). Ara h 2-binding B cells were enriched for IgG1 constant regions and expressed higher &lt;i&gt;FCER2&lt;/i&gt; compared to DT-binding counterparts.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Importantly, germline transcript of &lt;i&gt;IGHE&lt;/i&gt; was detected in most Ara h 2-binding B cells, indicating that the &lt;i&gt;IGHE&lt;/i&gt; locus was open and undergoing transcription, essential for IgE class switching upon antigen re-exposure. Ara h 2-binding IgG1 B cells were highly mutated, and monoclonal antibodies cloned from several of these cells were found to bind the same epitopes as previously identified IgE antibodies cross-reactive to peanut allergens.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Thus, these IgG1 B cells, expressing &lt;i&gt;FCER2&lt;/i&gt;, &lt;i&gt;IL4R&lt;/i&gt;, germline &lt;i&gt;IGHE&lt;/i&gt;, and with convergent BCR repertoires, potentially act as repository of IgE ASC precursors, providing a possible explanation for the maintenance of allergen-specific IgE.&lt;/p&gt;&lt;p&gt;Similar type 2","PeriodicalId":122,"journal":{"name":"Allergy","volume":"79 11","pages":"3173-3175"},"PeriodicalIF":12.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16278","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986953","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":"Recent patents in allergy and immunology: The interleukin-2 receptor pathway agonist rezpegaldesleukin (REZPEG) for the rescue of regulatory T cells in chronic inflammatory and autoimmune diseases","authors":"Christie Fanton,&nbsp;Jonathan Zalevsky","doi":"10.1111/all.16271","DOIUrl":"10.1111/all.16271","url":null,"abstract":"&lt;p&gt;Regulatory T cells (Tregs) hold a pivotal role in orchestrating immune homeostasis through their ability to modulate the activity of T helper cell subsets, but are impaired in many autoimmune and chronic inflammatory diseases including psoriasis (PsO) and atopic dermatitis (AD).&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; Interleukin-2 (IL-2) plays a role in controlling the proliferation and survival of Tregs,&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; with low-dose IL-2 shown to partially rescue Treg function and provide clinical benefit in autoimmune diseases.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Low-dose IL-2, however, has limited therapeutic practicality, including a narrow therapeutic window and short half-life, thereby requiring more frequent dosing that could, in turn, result in conventional CD4 and CD8 T cell (Tcon) induction.&lt;/p&gt;&lt;p&gt;The patent application&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; described herein provides therapeutically advantageous formulations, doses, and dosing regimens for rezpegaldesleukin (REZPEG), an IL-2 receptor (IL-2R) pathway agonist designed to stimulate the expansion and function of Tregs. REZPEG incorporates the approved recombinant human IL-2 (rhIL-2) aldesleukin sequence, which has been conjugated with stable, covalently attached polyethylene glycol (PEG) moieties (Figure 1). The result is a drug candidate having an extended half-life as well as a selectivity for Treg stimulation over Tcons compared with rhIL-2.&lt;span&gt;&lt;sup&gt;5, 6&lt;/sup&gt;&lt;/span&gt; The formulations, doses, and dosing regimens described in this patent include a range of fixed unit doses and regimens for induction and maintenance dosing. The objectives of these being to achieve effective autoimmune and chronic inflammatory disease management, increased patient compliance, convenience, and tolerability while also minimizing the risk of off-target Tcon stimulation.&lt;/p&gt;&lt;p&gt;In two randomized, double-blind, placebo-controlled Phase 1b trials in patients with AD or PsO, REZPEG was safe and well-tolerated, demonstrating consistent pharmacokinetics (PK) and clinical efficacy, meeting the primary, secondary, and exploratory objectives in both trials (NCT04081350 and NCT04119557). Notably, AD patients receiving 24 μg/kg REZPEG every 2 weeks (q2w) demonstrated an 83% improvement in Eczema Area and Severity Index (EASI) score after 12 weeks of treatment. EASI improvement of ≥75% (EASI-75) and validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) responses were maintained for 36 weeks after the end of the treatment period in 71% and 80% of patients responding to treatment at week 12, respectively. These clinical improvements were accompanied by sustained increases in CD25&lt;sup&gt;bright&lt;/sup&gt; Tregs over the 12-week treatment period.&lt;/p&gt;&lt;p&gt;We set about designing an IL-2-based biologic that could be used as a potential therapeutic to drive the proliferation and activation of Tregs over Tcons. We rejected a traditional drug discovery screening approach focused on in vitro ligand binding on our belief that it w","PeriodicalId":122,"journal":{"name":"Allergy","volume":"79 9","pages":"2565-2566"},"PeriodicalIF":12.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16271","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994810","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":"Comparison of two different pollen season definitions based on 10 years of birch and grass pollen data from two distant central European cities: An EAACI Task Force report","authors":"O. Pfaar,&nbsp;M. Bastl,&nbsp;M. Berger,&nbsp;U. E. Berger,&nbsp;K. Karatzas,&nbsp;T. Tasioulis,&nbsp;B. Werchan,&nbsp;M. Werchan,&nbsp;K. C. Bergmann,&nbsp;for the EAACI Task Force “Definition of clinical relevant thresholds of allergen exposure for analysis of outcomes in AIT”","doi":"10.1111/all.16252","DOIUrl":"10.1111/all.16252","url":null,"abstract":"&lt;p&gt;Start, duration, and intensity of different pollen seasons (PSs) can significantly differ between countries and regions with a high grade of annual variety over the longitudinal course.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; This is mainly influenced by factors such as climate, vegetation, urbanization, pollution, and others. The documentation of long-term changes in pollen flight is influenced by the method used to define a PS.&lt;/p&gt;&lt;p&gt;Airborne pollen is measured commonly using Hirst-type volumetric spore traps&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; according to national&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; and European Union standards.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; The results are usually expressed as average daily pollen concentrations of different pollen taxa (in pollen grains/m&lt;sup&gt;3&lt;/sup&gt; of air), which can be used to calculate the start and end of the PS. However, the above-mentioned variability of confounding factors is an obstacle to an overarching, generally accepted definition.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Several PS definitions, serving difference scientific purposes, are in use,&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; but have not been validated with respect to allergen immunotherapy (AIT).&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;In 2017, the European Academy of Allergy and Clinical Immunology (EAACI) published a Position Paper with threshold definitions for the start of PS, peak pollen period(s) (PPP[s]), high pollen day(s), and end of PS depending on the measured daily pollen concentrations and for the following pollen taxa: grasses, birch, olive, cypress, and ragweed.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; This definition was found to correlate significantly with the Total Nasal Symptom and Medication Score for grass and birch pollen-induced allergic rhinitis reported by users of electronic diaries (patient hay fever diaries [PHDs]) in Germany&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; as well as in Finland, Austria, and France.&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; Besides, defining a percentage of the seasonal pollen integral as start and end date as suggested by the European Aeroallergen Network (EAN) was found to be useful only in regions with exceptionally low pollen concentrations (so called percentage analysis [PA] in the following text).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The subsequent analysis of our EAACI Task Force on “Definition of clinical relevant thresholds of allergen exposure for analysis of outcomes in AIT” aimed to compare the two PS definition methods described above—EAACI and PA—when applied to 10 years of pollen data from the two distant cities of Berlin, Germany and Vienna, Austria, with the beeline between the cities being 524 km.&lt;/p&gt;&lt;p&gt;Birch and grass pollen concentrations were continuously monitored (2013–2022) in both cities using the monitoring method described above with Berlin showing higher pollen concentration compared to Vienna for both pollen taxa (Figure 1). The available data were used to conduct the following analyses for comparing the two PS methods: (i) start, end, and duration of PS (Figure 2), PPP(s), and hi","PeriodicalId":122,"journal":{"name":"Allergy","volume":"79 11","pages":"3161-3165"},"PeriodicalIF":12.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16252","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994808","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":"Correspondence: Proposed amendment to the nomenclature of allergic diseases and hypersensitivity reactions: Looking beyond the classic paradigms","authors":"Lucyna Mastalerz","doi":"10.1111/all.16277","DOIUrl":"10.1111/all.16277","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"79 11","pages":"3178-3179"},"PeriodicalIF":12.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986952","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":"Species-level, metagenomic and proteomic analysis of microbe-immune interactions in severe asthma","authors":"Maisha F. Jabeen,&nbsp;Nicholas D. Sanderson,&nbsp;Mariaenrica Tinè,&nbsp;Gillian Donachie,&nbsp;Clair Barber,&nbsp;Adnan Azim,&nbsp;Laurie C. K. Lau,&nbsp;Thomas Brown,&nbsp;Ian D. Pavord,&nbsp;Anoop Chauhan,&nbsp;Paul Klenerman,&nbsp;Teresa L. Street,&nbsp;Emanuele Marchi,&nbsp;Peter H. Howarth,&nbsp;Timothy S. C. Hinks","doi":"10.1111/all.16269","DOIUrl":"10.1111/all.16269","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The airway microbiome in severe asthma has not been characterised at species-level by metagenomic sequencing, nor have the relationships between specific species and mucosal immune responses in ‘type-2 low’, neutrophilic asthma been defined. We performed an integrated species-level metagenomic data with inflammatory mediators to characterise prevalence of dominant potentially pathogenic organisms and host immune responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sputum and nasal lavage samples were analysed using long-read metagenomic sequencing with Nanopore and qPCR in two cross-sectional adult severe asthma cohorts, Wessex (<i>n</i> = 66) and Oxford (<i>n</i> = 30). We integrated species-level data with clinical parameters and 39 selected airway proteins measured by immunoassay and O-link.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The sputum microbiome in health and mild asthma displayed comparable microbial diversity. By contrast, 23% (19/81) of severe asthma microbiomes were dominated by a single respiratory pathogen, namely <i>H. influenzae</i> (<i>n</i> = 10), <i>M. catarrhalis</i> (<i>n</i> = 4), <i>S. pneumoniae</i> (<i>n</i> = 4) and <i>P. aeruginosa</i> (<i>n</i> = 1). Neutrophilic asthma was associated with <i>H. influenzae, M. catarrhalis, S. pneumoniae</i> and <i>T. whipplei</i> with elevated type-1 cytokines and proteases; eosinophilic asthma with higher <i>M. catarrhalis</i>, but lower <i>H. influenzae</i>, and <i>S. pneumoniae</i> abundance. <i>H. influenzae</i> load correlated with Eosinophil Cationic Protein, elastase and IL-10. <i>R. mucilaginosa</i> associated positively with IL-6 and negatively with FGF. Bayesian network analysis also revealed close and distinct relationships of <i>H. influenzae</i> and <i>M. catarrhalis</i> with type-1 airway inflammation. The microbiomes and cytokine milieu were distinct between upper and lower airways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This species-level integrated analysis reveals central, but distinct associations between potentially pathogenic bacteria and airways inflammation in severe asthma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"79 11","pages":"2966-2980"},"PeriodicalIF":12.6,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16269","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141910898","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":"Assessment of sIgE to rLep d 2 for detecting Lepidoglyphus destructor sensitization.","authors":"Cristina Martin-Garcia, Andrea Dionelly Murillo-Casas, Milagros Lázaro-Sastre, Miguel Estravís, Francisco Javier Muñoz-Bellido, Elena Mazoteras-Martinez, Ignacio Dávila","doi":"10.1111/all.16272","DOIUrl":"https://doi.org/10.1111/all.16272","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141910897","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":"Alopecia areata exhibits cutaneous and systemic OX40 activation across atopic backgrounds.","authors":"Madeline Kim, Ester Del Duca, Dante Dahabreh, Daniel Lozano-Ojalvo, Britta Carroll, Meredith Manson, Swaroop Bose, Digpal Gour, Monali NandyMazumdar, Ying Liu, Mitchelle Yu Ekey, Amira Chowdhury, Michael Angelov, Benjamin Ungar, Yeriel Estrada, Emma Guttman-Yassky","doi":"10.1111/all.16268","DOIUrl":"https://doi.org/10.1111/all.16268","url":null,"abstract":"<p><strong>Background: </strong>Alopecia areata (AA) is a chronic, nonscarring hair-loss disorder associated with significant quality-of-life impairment and limited treatment options. AA has been recently linked to atopy and shown to exhibit both Th1- and Th2-driven inflammation. However, a comprehensive molecular and cellular characterization across blood and scalp compartments in both atopic and nonatopic patients is lacking.</p><p><strong>Methods: </strong>Lesional and nonlesional scalp biopsies obtained from AA patients with (n = 16) or without (n = 20) atopic history, and 17 demographically matched healthy controls were analyzed with RNA-seq, RT-PCR, and immunohistochemistry. Flow cytometry was also performed on peripheral blood mononuclear cells (PBMCs) from a subset of patients. Differential expression was defined using |fold-change| > 1.5 and false-discovery rate <0.05.</p><p><strong>Results: </strong>AA scalp exhibited robust upregulation of Th1- (IFNG, CXCL9, CXCL10, CXCL11) and Th2-related products (CCL26, CCR4, IL10, IL13, TSLP, TNFRSF4/OX40) and shared downregulation of hair keratins, regardless of atopic background, with variable Th17/Th22 modulation. AA patients with atopy exhibited greater inflammatory tone and Th2-skewing (IL10, IL13, IL33, CCR4, CCL26). Disease severity correlated significantly with immune and hair keratin biomarkers and with perifollicular cellular infiltrates. Cutaneous OX40/OX40L upregulation was paralleled by increases in circulating OX40⁺ and OX40L⁺ leukocytes, regardless of atopic background.</p><p><strong>Conclusion: </strong>Our results suggest some atopy-associated immune differences in AA and highlight the OX40 axis as a potential novel therapeutic target that may broadly benefit AA patients.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900175","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":"Mepolizumab depletes inflammatory but preserves homeostatic eosinophils in severe asthma","authors":"Michael Fricker,&nbsp;John Harrington,&nbsp;Sarah A. Hiles,&nbsp;Peter G. Gibson","doi":"10.1111/all.16267","DOIUrl":"10.1111/all.16267","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Eosinophils are key therapeutic targets in severe asthma that are suppressed by IL5 (mepolizumab) and IL5 receptor (benralizumab) blockade. The effect of IL5 pathway biologics on recently described homeostatic (hEOs) and inflammatory (iEOs) eosinophil subsets is unknown. We aimed to determine the relative impact of mepolizumab and benralizumab treatment on eosinophil subset and phenotype, and explore clinical associations of eosinophil subsets with severe asthma characteristics and treatment response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a cross-sectional observational study of severe asthma (eosinophilic <i>n</i> = 32, non-eosinophilic <i>n</i> = 23, mepolizumab-treated <i>n</i> = 25), with longitudinal follow-up of 30 eosinophilic participants at two timepoints (4–24 weeks, &gt;24 weeks) post-commencement of mepolizumab (<i>n</i> = 20) or benralizumab (<i>n</i> = 10). Blood hEOs and iEOs were measured by flow cytometry assessment of surface CD62L protein.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>iEO proportion was significantly lower in mepolizumab-treated participants in both the cross-sectional and longitudinal study. Mepolizumab and benralizumab depleted iEOs to a similar extent, however a significantly greater number of hEOs remained in mepolizumab participants at follow-up. Greater iEO proportion correlated with poorer asthma control in eosinophilic but not non-eosinophilic asthma. Higher residual iEO proportion correlated with poorer asthma control in mepolizumab-treated individuals. Reduced blood eosinophil viability was observed in around half of mepolizumab-treated participants, which was associated with significantly better asthma control and spirometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Mepolizumab depletes iEOs and reduces circulating eosinophil viability in severe asthma but preserves a residual population of circulatory hEOs. In contrast benralizumab depleted both iEOs and hEOs. Higher iEO abundance and eosinophil viability are associated with poorer clinical outcomes following mepolizumab-treatment. Monitoring circulating eosinophil phenotype and viability may be useful to predict biologic treatment response in severe asthma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"79 11","pages":"3118-3128"},"PeriodicalIF":12.6,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900176","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}