Clinical and Translational Allergy最新文献

{"title":"Comparative analysis of cysteine proteases reveals gene family evolution of the group 1 allergens in astigmatic mites","authors":"Ling Shi,&nbsp;Qing Xiong,&nbsp;Fu Kiu Ao,&nbsp;Tsz Yau Wan,&nbsp;Xiaojun Xiao,&nbsp;Xiaoyu Liu,&nbsp;Baoqing Sun,&nbsp;Anchalee Tungtrongchitr,&nbsp;Ting Fan Leung,&nbsp;Stephen Kwok Wing Tsui","doi":"10.1002/clt2.12324","DOIUrl":"https://doi.org/10.1002/clt2.12324","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Astigmatic mites contain potent allergens that can trigger IgE-mediated immune responses, leading to allergic diseases such as asthma, allergic rhinitis and atopic dermatitis. In house dust mites <i>Dermatophagoides pteronyssinus</i> and <i>Dermatophagoides farinae</i>, group 1 allergens (Der p 1 and Der f 1), characterized as papain-like cysteine proteases, have been defined as the major allergens that have high prevalence and potency. Previous studies of mite group 1 allergens mainly focused on identification, comparison of sequence and structure, as well as the investigation of cross-reactivity. To achieve a comprehensive view of mite group 1 allergens, we performed a comparative genomic analysis of all the cysteine proteases in six astigmatic mite species to elucidate the evolutionary relationships of group 1 allergens.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Based on the high-quality and annotated genomes, all the cysteine proteases in six astigmatic mite species were identified by sequence homology search. The phylogenetic relationships, gene synteny and expression levels were revealed by bioinformatic tools. The allergenicity of recombinant cysteine proteases was evaluated by enzyme-linked immunosorbent assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Tandem duplication was revealed as the major feature of cysteine protease gene evolution in astigmatic mites. The high IgE-binding capacity and the significant expression level of the cysteine protease DP_007902.01 suggested its potential as a novel group 1 allergen of <i>D. pteronyssinus</i>. In addition, gene decay events were identified in the skin-burrowing parasitic mite <i>Sarcoptes scabiei</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This comprehensive analysis provided insights into the evolution of cysteine proteases, as well as the component-resolved diagnosis of mite allergies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12324","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138634142","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":"Cognitive, neuropsychiatric and neurological alterations in mastocytosis: A systematic review","authors":"Elena Sagües-Sesé,&nbsp;Natalia García-Casares,&nbsp;Ivan Álvarez-Twose","doi":"10.1002/clt2.12319","DOIUrl":"10.1002/clt2.12319","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mastocytosis manifests with multisystemic symptoms, often involving the nervous system. Numerous cognitive, neuropsychiatric and neurological alterations have been reported in multiple observational studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a qualitative systematic literature review of reported data consulting the electronic databases Medline, Scopus, Web of Science, Cochrane, and BASE until June 2023.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We selected 24 studies in which the majority showed that a high proportion of mastocytosis patients suffer cognitive, neuropsychiatric and neurological alterations. The most common disorders and estimated ranges of frequency observed in adults were depression (68%–75%), anxiety, high stress or irritability (27%–54%), cognitive impairment (27%–39%, primarily affecting memory skills), and headaches (55%–69%). Attention challenges and learning difficulties were reported in children at a rate of 13%, while neurodevelopmental disorders occurred at rates of 8%–12%. Frequent white abnormalities in mastocytosis patients with concomitant psychocognitive symptoms have been reported although neuroimaging studies have been performed rarely in this population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Further studies with more comprehensive and homogeneous evaluations and neuroimaging and histological analysis should be performed for a better understanding of these manifestations. An earlier detection and proper management of these symptoms could greatly improve the quality of life of these patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138629651","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":"Sensitization to alpha-gal as a cause of idiopathic anaphylaxis","authors":"Thushali Ranasinghe,&nbsp;Inoka Sepali Aberathna,&nbsp;Jeewantha Jayamali,&nbsp;Thashmi Nimasha,&nbsp;Harshani Chathurangika,&nbsp;Deneshan Peranantharajah,&nbsp;Hashini Colambage,&nbsp;Gathsaurie Neelika Malavige,&nbsp;Chandima Jeewandara","doi":"10.1002/clt2.12309","DOIUrl":"https://doi.org/10.1002/clt2.12309","url":null,"abstract":"&lt;p&gt;The incidence of anaphylaxis continues to rise globally based on hospital data from Europe (Sweden), United States, Australia, Brazil and some Asian (Japan) countries.&lt;span&gt;&lt;sup&gt;1-4&lt;/sup&gt;&lt;/span&gt; However, the incidence is likely to be higher due to misdiagnosis, misclassification, and underreporting&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; and because allergies and anaphylaxis are being neglected in developing countries due to other disease priorities.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; In a large proportion of cases, after extensive evaluation, a trigger cannot be identified and are classified as ‘idiopathic anaphylaxis’ (IA). As food consumption patterns, genetic background, and environmental factors can lead to differences in allergen sensitization patterns in different geographical regions, we sought to identify possible triggers of IA in Sri Lankan patients presenting to a specialized allergy clinic.&lt;/p&gt;&lt;p&gt;All patients referred with a history of anaphylaxis were recruited following informed consent. The patients were evaluated for possible aetiological factors and contributing cofactors for the development of anaphylaxis. Relevant skin prick tests were conducted to identify the allergen. Those in whom a possible allergen could not be identified were classified as having idiopathic anaphylaxis. Accordingly, from January to December 2021, of 200 patients with anaphylaxis screened at the clinic, 65 patients were considered to have IA. In all patients, the events that led to the episode, the foods consumed, the severity of symptoms, and treatment received were recorded. Ethical approval was obtained from the Ethics Review Committee, Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Lanka. A blood sample was obtained from all patients on which an Immuno Solid-Phase Allergen Chip (ISAC) ImmunoCAP was performed. In patients whose ISAC was negative, a serum tryptase was done and results were within the normal range. Statistical analysis was done using GraphPad prism version 9.0.&lt;/p&gt;&lt;p&gt;Of the 65 patients, 42 (64.6%) were females and 49 (75.38%) were adults. Eight (12.3%) had grade 1 anaphylaxis, forty-six (70.8%) grade 2 anaphylaxis, and eleven (16.9%) grade 3 anaphylaxis. The allergen sensitization pattern is shown in (Table 1). Thirty-four (52.3%) patients were found to have specific IgE to alpha-gal. The other main allergens sensitized were house dust mites, twenty (30.8%), and grass pollen, sixteen (24.6%).&lt;/p&gt;&lt;p&gt;Allergy to Galactose-α-1,3-galactose (α-gal) has been shown as an important cause of anaphylaxis among those in whom a cause is unidentifiable.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Of the patients sensitized to alpha-gal, fourteen (41.2%) were male and twenty-two (64.7%) were adults. Sixteen (47.1%) did not have detectable IgE to other allergens included in the ISAC ImmunoCAP. Twelve (35.3%) had consumed mammalian meat prior to developing anaphylaxis, and therefore, alpha-gal allergy is most likely to be the trigger in these patients. Fourteen had consume","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12309","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138491420","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":"The efficacy and safety of oral microecological agents as add-on therapy for atopic dermatitis: A systematic review and meta-analysis of randomized clinical trials","authors":"Peiwen Xue,&nbsp;Haiyan Qin,&nbsp;Di Qin,&nbsp;Huilin Liu,&nbsp;Juan Li,&nbsp;Rongjiang Jin,&nbsp;Xianjun Xiao","doi":"10.1002/clt2.12318","DOIUrl":"https://doi.org/10.1002/clt2.12318","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;Atopic dermatitis (AD) is a common skin disease that is hard to completely cure in a short time. Guidelines recommend the use of topical corticosteroids (TCS) as first-line anti-inflammatory therapy for AD, but long-term use has significant side effects. Microecological agents (MA), including probiotics, prebiotics and synbiotics, have been widely reported as a potential adjunctive therapy of AD, but whether MA can contribute to AD treatment is currently controversial. Therefore, we conducted a systematic review and meta-analysis to investigate whether MA as an add-on therapy for AD has synergistic and attenuated effects and to further understand the role of MA in clinical interventions for AD.&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;We systematically searched Medline, Embase, Web of Science, Cochrane Library and PsycINFO databases up to Apr 11, 2023, and bibliographies were also manually searched, for potentially relevant studies regarding MA as additional therapy of AD. The Cochrane Risk of Bias Tool for assessing risk of bias was used to assess the quality of randomized controlled trials (RCTs). Two reviewers screened studies, extracted data, and evaluated the risk of bias independently. The primary outcomes (SCORAD scores and the number of adverse events) and the secondary outcomes (pruritus scores, the quality of life and the frequency of TCS) were extracted from each article. The data were combined and analyzed to quantify the safety and efficacy of the treatment. R (V4.4.3) software was used for data synthesis. The certainty of the evidence was evaluated with the Grade of Recommendation, Assessment, Development and Evaluation (GRADE) system. We also performed a trial sequential analysis to assess the reliability of the evidence.&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 21 studies, including 1230 individuals, were identified, 20 of which met the eligibility criteria for the meta-analysis. Our pooled meta-analyses showed that compared with controls, oral MA as an add-on therapy was associated with significantly lower SCORAD scores (MD = −5.30, 95% CI −8.50, −1.55, &lt;i&gt;p&lt;/i&gt; &lt; 0.01, &lt;i&gt;I&lt;/i&gt;&lt;sup&gt;&lt;i&gt;2&lt;/i&gt;&lt;/sup&gt; = 81%). However, adverse events, pruritus scores, quality of life, and frequency of TCS use showed no significant difference in this meta-analysis study (&lt;i&gt;p&lt;/i&gt; &gt; 0.05).&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;This meta-analysis showed that MA plus TCS could be an effective and safe treatment for patients with AD to relieve relevant symptoms, which might be use","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138480850","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":"Asthma is associated with increased severity and duration of rhinitis: A study with the Allergic Rhinitis and its Impact on Asthma classes in the Constances cohort","authors":"Marine Savouré,&nbsp;Jean Bousquet,&nbsp;Bénédicte Leynaert,&nbsp;Céline Ribet,&nbsp;Marcel Goldberg,&nbsp;Marie Zins,&nbsp;Bénédicte Jacquemin,&nbsp;Rachel Nadif","doi":"10.1002/clt2.12316","DOIUrl":"https://doi.org/10.1002/clt2.12316","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Few population-based studies have described allergic rhinitis (AR) according to the Allergic Rhinitis and its Impact on Asthma (ARIA) classification, and none have assessed the impact of asthma on this classification. Our aims were to 1) describe AR according to four ARIA classes and 2) within each of the four ARIA classes, compare participants with AR alone versus those with AR and asthma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cross-sectional analyses were performed using data from the 2014 annual follow-up questionnaire of the French adult population-based cohort Constances. Current AR was defined by the report of sneezing, runny, or blocked nose in the last 12 months and the report of nasal allergies. Following ARIA recommendations, rhinitis was classified according to its severity (mild or moderate-severe) and duration (intermittent or persistent). Ever asthma was also defined by a questionnaire.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 4675 participants with AR (57% women, mean age 50.2 ± 12.7 years), 44% were classified as mild/intermittent, 16% mild/persistent, 25% moderate-severe/intermittent, and 15% moderate-severe/persistent. Within each of the four ARIA classes, compared to participants with rhinitis alone, participants with rhinitis and asthma had significantly more severe symptoms, more conjunctivitis, a higher mean eosinophil count and more treatments with intra-nasal corticosteroids and oral antihistamines co-medication.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This is a paradigm shift study as for the first time this large population-based study in adults showed that asthma status has a profound effect on the ARIA classification. Rhinitis alone and rhinitis with asthma represent two distinct phenotypes. These results reinforce the need to include asthma status in the ARIA classification and guidelines.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12316","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138432294","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":"Application of a dried blood spot based proteomic and genetic assay for diagnosing hereditary angioedema","authors":"Marius-Ionuţ Iuraşcu,&nbsp;Zsuzsanna Balla,&nbsp;Catarina Pereira,&nbsp;Noémi Andrási,&nbsp;Lilian Varga,&nbsp;Dorottya Csuka,&nbsp;Ágnes Szilágyi,&nbsp;Kornelia Tripolszki,&nbsp;Suliman Khan,&nbsp;Iuliana Susnea,&nbsp;Peter Bauer,&nbsp;Claudia Cozma,&nbsp;Henriette Farkas","doi":"10.1002/clt2.12317","DOIUrl":"https://doi.org/10.1002/clt2.12317","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hereditary angioedema (HAE) with C1-inhibitor deficiency (C1-INH-HAE) is a rare disease caused by low level (type I) or dysfunction (type II) of the C1-inhibitor protein with subsequent reduction of certain complement protein levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To develop and test the reliability of a two-tier method based on C1-INH and C4 quantitation followed by genetic analysis from dried blood spot (DBS) for establishing the diagnosis of C1-INH-HAE. C1-INH and C4 proteins have been quantified in human plasma using a classical immuno-assay and in DBS using a newly developed proteolytic liquid chromatography–mass spectrometry method. Genetic analysis was carried out as reported previously (PMID: 35386643) and by a targeted next-generation sequencing panel, multiplex ligation-dependent probe amplification and in some cases whole genome sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DBS quantification of C1-INH and C4 showed the same pattern as plasma, offering the possibility of screening patients with AE symptoms either locally or remotely. Genetic analysis from DBS verified each of the previously identified <i>SERPING1</i> mutations of the tested C1-INH-HAE patients and revealed the presence of other rare variations in genes that may be involved in the pathogenesis of AE episodes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>C1-INH/C4 quantification in DBS can be used for screening of hereditary AE and DNA extracted from dried blood spots is suitable for identifying various types of mutations of the <i>SERPING1</i> gene.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12317","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138432293","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":"A robust mRNA signature obtained via recursive ensemble feature selection predicts the responsiveness of omalizumab in moderate-to-severe asthma","authors":"Sarah Kidwai,&nbsp;Pietro Barbiero,&nbsp;Irma Meijerman,&nbsp;Alberto Tonda,&nbsp;Paula Perez-Pardo,&nbsp;Pietro Lio ́,&nbsp;Anke H. van der Maitland-Zee,&nbsp;Daniel L. Oberski,&nbsp;Aletta D. Kraneveld,&nbsp;Alejandro Lopez-Rincon","doi":"10.1002/clt2.12306","DOIUrl":"https://doi.org/10.1002/clt2.12306","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Not being well controlled by therapy with inhaled corticosteroids and long-acting β2 agonist bronchodilators is a major concern for severe-asthma patients. The current treatment option for these patients is the use of biologicals such as anti-IgE treatment, omalizumab, as an add-on therapy. Despite the accepted use of omalizumab, patients do not always benefit from it. Therefore, there is a need to identify reliable biomarkers as predictors of omalizumab response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Two novel computational algorithms, machine-learning based Recursive Ensemble Feature Selection (REFS) and rule-based algorithm Logic Explainable Networks (LEN), were used on open accessible mRNA expression data from moderate-to-severe asthma patients to identify genes as predictors of omalizumab response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>With REFS, the number of features was reduced from 28,402 genes to 5 genes while obtaining a cross-validated accuracy of 0.975. The 5 responsiveness predictive genes encode the following proteins: Coiled-coil domain- containing protein 113 (<i>CCDC113</i>), Solute Carrier Family 26 Member 8 (<i>SLC26A</i>), Protein Phosphatase 1 Regulatory Subunit 3D (<i>PPP1R3D</i>), C-Type lectin Domain Family 4 member C (<i>CLEC4C</i>) and <i>LOC100131780</i> (not annotated). The LEN algorithm found 4 identical genes with REFS: <i>CCDC113, SLC26A8 PPP1R3D</i> and <i>LOC100131780</i>. Literature research showed that the 4 identified responsiveness predicting genes are associated with mucosal immunity, cell metabolism, and airway remodeling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion and clinical relevance</h3>\u0000 \u0000 <p>Both computational methods show 4 identical genes as predictors of omalizumab response in moderate-to-severe asthma patients. The obtained high accuracy indicates that our approach has potential in clinical settings. Future studies in relevant cohort data should validate our computational approach.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12306","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137691337","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":"Exercise-induced eosinophil responses: Normal cell counts with a marked decrease in responsiveness","authors":"Bernard N. Jukema,&nbsp;Thomas C. Pelgrim,&nbsp;Sylvan L. J. E. Janssen,&nbsp;Thijs M. H. Eijsvogels,&nbsp;Alma Mingels,&nbsp;Wim Vroemen,&nbsp;Nienke Vrisekoop,&nbsp;Leo Koenderman","doi":"10.1002/clt2.12314","DOIUrl":"https://doi.org/10.1002/clt2.12314","url":null,"abstract":"&lt;p&gt;To the Editor,&lt;/p&gt;&lt;p&gt;Type II inflammation is characterized by elevated blood eosinophils which makes these cells an important diagnostic and treatment target in, for instance, severe asthma. Therefore, blood eosinophil numbers are a main inclusion criterion for many clinical studies that have investigated the treatment of eosinophilic asthma with, for example, anti-IL5(Rα).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; However, there is no consensus on cut-off values for blood eosinophils at inclusion as evidenced by a high variability between studies, ranging from 150 to 400 cells/μL. Moreover, the range of blood eosinophils in a healthy population, without confounding factors for increased blood eosinophils, is 30–330 cells/μL in males and 30–310 cells/μL in females.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; This implies that the cut-off values used for clinical studies greatly overlap with blood eosinophil counts that are found in the healthy population. This inherently poses a problem as eosinophil blood counts seem to be inadequate to use for diagnosing eosinophilic diseases other than hypereosinophilia (&gt;1500 cells/μL).&lt;/p&gt;&lt;p&gt;This overlap in eosinophil counts between patients and the healthy population limits the application of eosinophil numbers for discriminating between health and several inflammatory diseases. Eosinophil activation status ex vivo has already been investigated primarily with regard to asthma phenotypes,&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; but this study did not account for the effects of ex vivo activation caused by the manipulation of cells during sample work-up procedures. So, at least part of the activation phenotype might have been caused by enhanced sensitivity for ex vivo activation under these inflammatory conditions. Thus, a more promising approach in diagnosing eosinophilic disease would be to combine eosinophil numbers with their activation status under controlled conditions with minimal ex vivo manipulation.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; This could improve eosinophil diagnostics, particularly in situations with (relative) eosinopenia. Unfortunately, there is surprisingly little evidence that blood eosinophil &lt;i&gt;counts&lt;/i&gt; correlate with their activation status and/or responsiveness in vivo. Apart from activation ex vivo,&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; this lack of correlation can also be caused by homing of activated cells to the lung leaving behind non-activated cells in the blood.&lt;span&gt;&lt;sup&gt;4, 6&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Most studies on eosinophil activation in vivo have been performed in the context of T-2 diseases. These studies imply that eosinophil activation in vivo is mainly driven by T-2 cytokines such as IL-5. Surprisingly little is known about eosinophil activation in vivo in donors without inflammatory diseases. Therefore, we designed this study on eosinophil activation in healthy individuals. Minimal ex vivo activation was achieved by analyzing blood eosinophils directly after venipuncture with a fast, automated, point-of-care, mobile flow cytometer (AQUIOS","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12314","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134879447","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":"A high-dose, depigmented polymerized birch pollen extract for subcutaneous allergen immunotherapy has a favourable efficacy/safety ratio","authors":"Oliver Pfaar,&nbsp;Angelika Sager,&nbsp;Ralph Mösges,&nbsp;Margitta Worm","doi":"10.1002/clt2.12315","DOIUrl":"https://doi.org/10.1002/clt2.12315","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Subcutaneous allergen immunotherapy (SCIT) with depigmented, polymerized (DPP) birch pollen extract has been marketed at doses of up to 1000 DPP units/mL since 2001. We sought to determine the dose-dependent efficacy of a DPP birch pollen extract formulation in patients suffering from birch-pollen-induced allergic rhinitis or rhinoconjunctivitis with or without intermittent asthma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A titrated conjunctival provocation test (CPT) was applied as a surrogate marker. This Phase II randomized, double-blind, parallel-group, dose-ranging clinical trial was performed at 39 centres in Germany, Lithuania and Poland. After randomization to four dose-level groups (100, 1000, 5000 and 10,000 DPP units/mL) and up-dosing, participants received maintenance SCIT with five monthly subcutaneous injections. The primary endpoint was the proportion of patients in whom a higher concentration of birch pollen (vs. baseline) was needed to elicit a positive CPT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Three hundred forty-three patients were included (mean (range) age: 42.6 (19–70)). The highest CPT responder rates were seen in the higher dose-level groups. In the intention-to-treat analysis, the difference between the 100 and 10,000 groups was statistically significant (<i>p</i> = 0.0118). Although the proportion of patients with ≥1 treatment-emergent adverse events increased with the dose, almost all these events were mild (65.6%) or moderate (18.5%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Judging by the results of a CPT, the efficacy/safety ratio in SCIT appears to be favourable for a high-dose-level preparation of a DPP birch pollen extract.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"109169667","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":"Epidemiology and treatment of children with hereditary angioedema in Germany: A retrospective database study","authors":"Freerk Prenzel,&nbsp;Susanne Abraham,&nbsp;Christoph Hirche,&nbsp;Gerrit Müller,&nbsp;Stephan Kaiser,&nbsp;Leonarda Serdani-Neuhaus,&nbsp;Rebecca Zingel,&nbsp;Inmaculada Martinez-Saguer","doi":"10.1002/clt2.12313","DOIUrl":"https://doi.org/10.1002/clt2.12313","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hereditary angioedema (HAE) is a potentially life-threatening inherited disease that causes recurrent, serious, and debilitating episodes of swelling. While evidence has improved in adult patients, data on the epidemiology and treatment of pediatric patients with HAE remain very limited. The aim of this study was to determine the incidence and prevalence of pediatric patients with HAE aged &lt;12 years, as well as treatment patterns, co-medication, and specialties involved.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this retrospective study (2016–2021), the German IQVIA^TM pharmacy claims (LRx) database was used to analyze prescriptions of HAE-specific treatments and co-medications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found an HAE prevalence in pediatric patients aged &lt;12 years of 2.51:100,000 and a 12-month prevalence of up to 1.02:100,000 between 2016 and 2021. Most HAE treatments were prescribed by outpatient clinics and pediatricians, with an increasing proportion of icatibant as an on-demand treatment and low rates of long-term prophylaxis (LTP). The prescription rate of analgesics as the most common co-medication decreased notably after HAE diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings provide insights into the epidemiology and current pediatric HAE treatment landscape in Germany. The obtained HAE prevalence in pediatric patients aged &lt;12 years was even higher than the previously reported average of overall cohorts, whereas the LTP rate was low, which might indicate an unmet need for newer LTP treatment options in pediatric patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12313","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"109168475","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}