Journal of Allergy and Clinical Immunology最新文献

{"title":"Fine resolution of the N-terminal IgE-binding epitope of Ara h 2: discovery of variants with enhanced IgE binding.","authors":"Joshua S Bernstein,Nicole Canon,Catherine H Schein,Werner Braun,Surendra S Negi,Raffi Tchekmedyian,Marina Pozzoli,Edwin H Kim,Michael D Kulis,Thao Vu,Weimin Liu,Xueni Chen,Stephen C Dreskin","doi":"10.1016/j.jaci.2025.03.032","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.03.032","url":null,"abstract":"BACKGROUNDIgE binding to linear peptides from the N-terminal region of Ara h 2 (epitope 1) is associated with the achievement of sustained unresponsiveness (SU) in young children receiving oral immunotherapy (OIT) and may be important for cross-reactivity between peanuts and tree nuts. This region is also part of the binding site for neutralizing IgG monoclonal antibodies associated with SU following OIT.OBJECTIVETo perform alanine scanning of this epitope to determine the importance of individual amino acids and then amino acid scanning to screen for sequences with enhanced binding of IgE.METHODSA streptavidin IgE ELISA with biotinylated peptides was used to measure the binding of IgE to full length and truncated peptides in order to identify a core sequence (DRRCQSQLERAN). Peptide microarrays were used to screen multiple peptides and quantitate binding of IgE. Statistical analysis included one way ANOVA followed by Dunnett's multiple comparison test.RESULTSIgE binding was greatly reduced when alanine was substituted for arginine at positions 2, 3 and 10 (R2, P<0.001, R3, P<0.01, R10, P<0.001), glutamine at position 5 and 7 (Q5, P<0.01, Q7, P<0.001) and glutamate at position 9 (E9, P<0.01). Substitution of aspartate with asparagine at position 1 in conjunction with substitution of asparagine at position 12 with either leucine or lysine gave enhanced binding (p<0.0001). Molecular modeling of these data suggests a conformational basis for recognition by polyclonal IgE.CONCLUSIONSIgE binding assays using pooled and individual sera demonstrated the importance of aa throughout the sequence of epitope 1 for immune recognition. The results of alanine scanning indicated residues that could be changed as part of a larger strategy to generate hypoallergenic forms of Ara h 2 while sequence variants with enhanced binding were identified that may be useful for improving diagnostics.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"92 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902888","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":"Reply.","authors":"Nandinee Patel, Paul J Turner","doi":"10.1016/j.jaci.2025.03.031","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.03.031","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007174","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":"Food allergy endotypes revisited.","authors":"Mary Grace Baker, Lydia Su Yin Wong, George N Konstantinou, Anna Nowak-Wegrzyn","doi":"10.1016/j.jaci.2025.04.019","DOIUrl":"10.1016/j.jaci.2025.04.019","url":null,"abstract":"<p><p>In the last century, food allergy has become recognized as an increasingly prevalent and heterogeneous condition. Advances in biomedical technology have revealed complex genetic, environmental, immune, and metabolic pathways underlying the pathogenesis of food-allergic disorders. These findings permit classification of distinct food allergy endotypes with unique pathophysiologic features. In this review, we suggest that these endotypes of food-allergic disorders should be defined on the basis of (1) whether or not the allergic antibody IgE plays an essential role in disease pathogenesis, (2) the molecular features of the allergen (protein vs carbohydrate), and (3) the molecular markers associated with prognosis, severity, or clinical presentation. Beyond these broad categories, additional subtypes with unique mechanistic characteristics are discussed.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025450","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":"Epinephrine delivery devices: Pharmacokinetics and pharmacodynamics.","authors":"John M Kelso","doi":"10.1016/j.jaci.2025.03.030","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.03.030","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"91 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889320","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":"Lessons from the clinical use of ex vivo T-lymphopoiesis assays.","authors":"Grace Evans,Zainab M Golwala,Juan Moises Ocampo-Godinez,Alexandra Y Kreins","doi":"10.1016/j.jaci.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.008","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"9 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889308","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":"Complement dysregulation at lymphatics.","authors":"Ahmet Ozen, Salim Can, Asena Pinar Sefer, Necmiye Keser Ozturk, Burkay Cagan Colak","doi":"10.1016/j.jaci.2025.04.020","DOIUrl":"10.1016/j.jaci.2025.04.020","url":null,"abstract":"<p><p>The complement system is a central component of innate immunity, orchestrating pathogen clearance while regulating inflammation, tissue repair, and homeostasis. Its activation is tightly controlled by multiple inhibitors to prevent self-damage. However, complement dysregulation is implicated in numerous organ-specific diseases, including paroxysmal nocturnal hemoglobinuria (erythrocytes), atypical hemolytic uremic syndrome (kidneys), and age-related macular degeneration (eyes). Recent discoveries have revealed that complement hyperactivation also drives lymphatic dysfunction, most notably in CHAPLE (CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy) disease-a rare pediatric disorder caused by biallelic CD55 mutations. Impaired regulation of C3 and C5 convertases leads to unchecked complement and coagulation activation, resulting in membrane attack complex deposition, severe intestinal lymphangiectasia, and protein-losing enteropathy. Patients typically present with hypoalbuminemia, edema, gastrointestinal symptoms, growth retardation, and recurrent thromboembolic events, reflecting a severe thrombophilic phenotype. C5-blocking antibodies, including pozelimab and eculizumab, transformed CHAPLE management. In a phase 2/3 study, pozelimab led to normalization of serum albumin levels and notable reductions in hospitalizations and transfusion needs, leading to Food and Drug Administration approval. Emerging evidence suggests that complement-driven protein-losing enteropathy may also arise in other pathological contexts, expanding the clinical impact of complement dysregulation. As research progresses, novel diagnostic and therapeutic strategies are expected to emerge for a broader spectrum of complement-mediated lymphatic disorders.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025907","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":"Probing the diagnosis of SCID through in vitro T-cell development: experience in two centers in North America.","authors":"Clara Soulard,Francesca Pala,Marita Bosticardo,Elie Haddad","doi":"10.1016/j.jaci.2025.04.021","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.021","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"222 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889293","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":"Selective JAK1 inhibition remits multiorgan autoimmunity in a patient with refractory autoimmune polyendocrine syndrome type 1.","authors":"Yannis Hadjiyannis,Madison N Martinez,Joseph Pechacek,Ibrahim Abukhiran,Deanna Riley,Stefania Pittaluga,Elena M Morariu,Michail S Lionakis,David G Binion,Reed Van Deusen","doi":"10.1016/j.jaci.2025.03.026","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.03.026","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"1 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872022","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":"Clarification of the efficacy of tezepelumab in the phase 2a COURSE trial.","authors":"Dave Singh,MeiLan K Han,Jean-Pierre Llanos,Neil Martin,Amit Parulekar,Konstantinos Kostikas,Sandhia S Ponnarambil","doi":"10.1016/j.jaci.2024.12.1086","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.12.1086","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"32 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866831","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":"Metabotypes are linked to uncontrolled childhood asthma, gut microbiota, and systemic inflammation.","authors":"Mahmoud I Abdel-Aziz,Simone Hashimoto,Anne H Neerincx,Eric G Haarman,Alexander Cecil,Jutta Lintelmann,Michael Witting,Stefanie M Hauck,Nikki Kerssemakers,Joris C Verster,Corinna Bang,Andre Franke,Barbara S Dierdorp,Tamara Dekker,Nariman K A Metwally,Jan Willem Duitman,René Lutter,Mario Gorenjak,Antoaneta A Toncheva,Parastoo Kheiroddin,Susanne Harner,Susanne Brandstetter,Christine Wolff,Paula Corcuera-Elosegui,Leyre López-Fernández,Javier Perez-Garcia,Mario Martin Almeida,Olaia Sardón-Prado,Maria Pino-Yanes,Uroš Potočnik,Michael Kabesch,Susanne J H Vijverberg,Aletta D Kraneveld,Anke H Maitland-van der Zee,","doi":"10.1016/j.jaci.2025.04.017","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.017","url":null,"abstract":"BACKGROUNDChildhood asthma has been linked to distinct metabolomic profiles.OBJECTIVETo identify phenotypes (metabotypes) in children with moderate-to-severe asthma through integrative fecal and serum metabolome analysis.METHODSChildren from the Systems Pharmacology Approach to Uncontrolled Pediatric Asthma cohort with Global Initiative for Asthma treatment step ≥3 were recruited. Asthma control was defined by the Asthma Control Test and annual exacerbation history. Targeted metabolomics profiling of feces and serum was performed using liquid chromatography and flow injection electrospray ionization-triple quadrupole mass spectrometry. Similarity Network Fusion integrated fecal and serum metabolome profiles, followed by spectral clustering. Clusters were analyzed for differences in asthma characteristics, food diaries, fecal microbiota composition, and levels of serum inflammatory markers and blood cells.RESULTSIntegrative fecal and serum metabolome analysis of 92 children with moderate-to-severe asthma (median age: 11.5 years, 34% female) revealed three metabotypes. Metabotype1 had the lowest percentage of allergic rhinitis, with elevated serum ceramides and triglycerides. Metabotype2 had higher odds of asthma control, the highest percentage of children with ≥4 months of breastfeeding, reduced sugar intake, lowest levels of blood neutrophils and serum inflammatory markers, and with elevated serum acylcarnitines and ω-3 fatty acids. Metabotype3 included the highest percentage of uncontrolled asthma patients, with decreased serum cholesteryl esters, phosphatidylcholines, and sphingomyelins, elevated fecal amino acids, and reduced fecal microbiota diversity.CONCLUSIONSMetabotypes in children with moderate-to-severe asthma are linked to asthma control, distinct fecal microbiota and systemic inflammatory patterns. The findings suggest that metabotyping can be valuable in precision medicine approaches for asthma.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"19 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884939","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}