Journal of Allergy and Clinical Immunology最新文献

{"title":"Endotypes of Atopic Dermatitis.","authors":"Nanna Fyhrquist, Ying Yang, Piia Karisola, Harri Alenius","doi":"10.1016/j.jaci.2025.02.029","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.029","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a chronic, heterogeneous skin condition driven by a combination of genetic, immune, and environmental factors. The original classification into extrinsic and intrinsic endotypes has proven overly simplistic. Recent research into the varied immune profiles and molecular signatures of AD has revealed distinct endotypes - subtypes defined by specific biological processes rather than visible symptoms alone. These endotypes encompass classifications based on immune pathways, including Th2-dominant, Th1, Th17/Th22-driven responses, genetic factors, and microbial interactions. Recognizing these endotypes has become essential for advancing personalized treatments, as each subtype responds differently to immune-modulating therapies. Current treatment options, such as moisturizers, immunosuppressants, and biologics, show varied efficacy across AD endotypes, underscoring the need for more precise, endotype-specific approaches. Emerging molecular profiling technologies offer promising avenues to identify distinct biomarkers, refining AD classification and paving the way for more targeted treatments and improved patient outcomes.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584861","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":"Epicutaneous immunotherapy with VIASKIN patch for peanut allergy: Permeability via intact skin.","authors":"Christophe Dupont, Hugh A Sampson","doi":"10.1016/j.jaci.2025.01.038","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.038","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567162","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":"The Drug Allergy History Tool (DAHT): Validation of a Patient-Reported Survey Instrument.","authors":"Kimberly G Blumenthal, Daniel A Gundersen, Liam R Smith, Brett Nava-Coulter, Andrew King, Elizabeth J Phillips, Alexei Gonzalez-Estrada, Iris M Otani, Allison Ramsey, Aleena Banerji, Timothy Chow, Cosby A Stone, Whitney A Salinas, David A Khan","doi":"10.1016/j.jaci.2025.02.027","DOIUrl":"10.1016/j.jaci.2025.02.027","url":null,"abstract":"<p><strong>Background: </strong>While the reaction history is critical for drug allergy evaluations and is typically self-reported, there is no validated survey instrument to collect drug allergy history from patients.</p><p><strong>Objective: </strong>To validate a survey instrument that collects patient-reported drug allergy history.</p><p><strong>Methods: </strong>The Drug Allergy History Tool (DAHT) was revised after three rounds of cognitive testing, with data assessed for reliability, through test-retest comparison, and quality and validity, through a concordance analysis against electronic health record (EHR) allergist documentation. Participants completing testing and surveys were recruited from drug allergy clinics at Massachusetts General Hospital. Primary evaluative measures were percent agreement and Kappa statistic values.</p><p><strong>Results: </strong>The DAHT was completed by 79 individuals (mean age 49 [SD 17] years, 85% Female, 85% White, 11% Hispanic ethnicity); 29 with single-drug allergy labels and 50 with multiple drug allergy labels. The most common drug allergy labels were penicillins (77%), sulfonamides (32%), cephalosporins (15%), and nonsteroidal anti-inflammatory drugs (8%). DAHT achieved acceptable test-retest reliability (median Kappa = 0.64, median percent agreement = 86%). The DAHT achieved a more complete allergy history than the allergist documentation in the EHR with lower median item uncertainty (21% DAHT vs 79% EHR) with fair concordance (median Kappa = 0.21, median percent agreement = 67%) between the two data sources.</p><p><strong>Conclusion: </strong>The DAHT is a reliable and valid source of patient-reported allergy information. This tool can be used in clinical care and clinical research to obtain standardized patient reported drug allergy history.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572974","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":"Predicting future exacerbations in uncontrolled asthma: a discovery/validation approach using large-scale clinical proteomics.","authors":"Lisa M Jurak, Ian A Yang, Jodie L Simpson, Peter G Gibson, Michelle M Hill, John W Upham","doi":"10.1016/j.jaci.2025.02.028","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.028","url":null,"abstract":"<p><strong>Background: </strong>Exacerbations contribute significantly to the burden of asthma. Some individuals are predisposed to recurring exacerbations however, the underlying mechanisms are not well understood.</p><p><strong>Objective: </strong>To generate a sputum protein signature associated with future exacerbations.</p><p><strong>Method: </strong>22 baseline sputum samples from the control (placebo control) arm of the AMAZES study were analysed using an optimised high-throughput mass spectrometry method.</p><p><strong>Results: </strong>Using a log-fold change of ≥ 1.5 and a p-value of 0.05 as cut-offs, univariate analysis identified 533 differentially abundant sputum proteins in participants with and without future exacerbations over the ensuring 48 weeks. A multivariate signature of 260 proteins for predicting future exacerbations was developed using sparse partial least squares data analysis, that was partially able to predict those who would likely experience an exacerbation with an area under the receiver-operating curve of 0.95 and an error rate of 0.41. Next, the 20 most influential proteins were selected for validation and quantification in sputum from an additional 123 participants. Upon validation, 9 proteins were found to be linked to future exacerbation risk. The final model could predict future exacerbations with an area under the receiver-operating curve of 0.77 with an error rate of 0.40. Pathway analysis revealed major themes associated with exacerbations including inflammation, recruitment, and proliferation of immune cells.</p><p><strong>Conclusion: </strong>This study has identified for the first time a sputum proteomic signature and pathways associated with future exacerbations, which will facilitate the discovery of new biomarkers and novel therapeutic targets in uncontrolled persistent asthma.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572970","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":"Prior SARS-Cov-2 infection affects adaptive immune responses to Omicron BA.4/BA.5 mRNA booster.","authors":"Brianna T Wachter, Qin Xu, Lihong Shi, Peter D Burbelo, Kathy Myint-Hpu, Pamela L Schwartzberg, Muhammad Tauseef Rehman, Robin L Dewar, Kristin L Boswell, Richard A Koup, Cihan Oguz, Luisa Imberti, Lorenza Bellusci, Sara Pourhashemi, Surender Khurana, Kalpana Manthiram, Luigi D Notarangelo, Ottavia M Delmonte","doi":"10.1016/j.jaci.2025.02.026","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.026","url":null,"abstract":"<p><strong>Background: </strong>Bivalent COVID-19 mRNA vaccines encoding Wuhan-1 and Omicron BA.4/5 spike proteins can prevent SARS-CoV-2 infection, but the quality of adaptive immune responses and the importance of hybrid immunity are not well-documented.</p><p><strong>Objectives: </strong>Adaptive immune responses to the bivalent vaccine were studied in 40 healthy participants with (COVID+) or without (COVID-) prior history of SARS-CoV-2 infection.</p><p><strong>Methods: </strong>We analyzed anti-N and anti-S IgG titers and surrogate virus neutralization capacity against variants of concern (VOCs) and assessed SARS-CoV-2 specific B and T cell responses by high-dimensional spectral flow cytometry, intracellular cytokine staining assay upon stimulation with SARS-CoV-2 peptides and TRB and IGH repertoire analysis.</p><p><strong>Results: </strong>The COVID+ group had higher anti-S IgG levels pre- and post-booster and higher neutralization activity against BA.4/5 than the COVID- group. Spike antibody levels positively correlated with neutralizing activity against Omicron VOCs in all participants. For VOCs, lowest neutralization capacity was against XBB1.5. At baseline, the proportion of S1+ RBD+ B cells was higher in COVID+ than in COVID- subjects, but an increase of these cells post-boost was detected only in the COVID- group. Consistent with natural infection, COVID+ subjects had a higher frequency of IgA+ CXCR3+S1+RBD+ B cells at baseline than COVID- subjects. CD4+ memory T cells responses and breath of class II epitope SARS-CoV-2 specific clonotypes were increased post-boost only in COVID- participants.</p><p><strong>Conclusions: </strong>The bivalent vaccine induces robust adaptive immune responses against the Omicron variant. Prior SARS-CoV-2 infection provides increased protection, but optimal timing of booster administration after natural infection should be defined to maximize benefits.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567166","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":"Analysis of human neutrophils from nasal polyps by single-cell RNA sequencing reveals roles of neutrophils in chronic rhinosinusitis","authors":"Naruhito Iwasaki MD, PhD ,&nbsp;Julie A. Poposki MS ,&nbsp;Masanori Kidoguchi MD, PhD ,&nbsp;Aiko Oka MD, PhD ,&nbsp;Aiko I. Klingler PhD ,&nbsp;Whitney W. Stevens MD, PhD ,&nbsp;Lydia A. Suh MS ,&nbsp;Junqin Bai PhD ,&nbsp;Anju T. Peters MD ,&nbsp;Leslie C. Grammer MD ,&nbsp;Kevin C. Welch MD ,&nbsp;Stephanie S. Smith MD ,&nbsp;David B. Conley MD ,&nbsp;Bruce S. Bochner MD ,&nbsp;Robert P. Schleimer PhD ,&nbsp;Robert C. Kern MD ,&nbsp;Bruce K. Tan MD, MS ,&nbsp;Atsushi Kato PhD","doi":"10.1016/j.jaci.2024.10.032","DOIUrl":"10.1016/j.jaci.2024.10.032","url":null,"abstract":"<div><h3>Background</h3><div>Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 (T2) inflammation. Recent studies, including our own, suggest that neutrophils are also elevated in T2 nasal polyps (NP) and that elevated neutrophils display an activated phenotype. However, the actual roles of neutrophils in NP pathogenesis in T2 CRSwNP are still largely unclear.</div></div><div><h3>Objective</h3><div>To reveal the roles and heterogeneity of neutrophils in NP tissue by single-cell RNA sequencing analysis.</div></div><div><h3>Methods</h3><div>We developed a novel microwell-based single-cell RNA sequencing assay using granulocyte-enriched samples from 5 control sinus tissues, 5 NP tissues and patient-matched peripheral blood (PB) samples. This approach allowed for examination of differential expression of genes in NP neutrophils by the Benjamini-Hochberg algorithm and predicted the overall function of NP neutrophils by pathway and Gene Ontology enrichment analyses.</div></div><div><h3>Results</h3><div>After performing all quality control steps, we successfully detected neutrophils. We identified 333 downregulated and 128 upregulated genes in NP neutrophils (1,151 cells) compared with all PB neutrophils (13,591 cells) (&gt;1.5-fold, <em>q</em> &lt; 0.05) and found commonly dysregulated genes in NP neutrophils compared with both all PB and control sinus tissue neutrophils (3,136 cells). Commonly downregulated genes in NP neutrophils were associated with the innate immune system, and upregulated genes were associated with nuclear factor-κB signaling, cytokine activity, and cellular response to oxygen-containing compounds. NP neutrophils displayed 4 clusters revealing potential heterogeneity of neutrophils in NP tissue.</div></div><div><h3>Conclusions</h3><div>Elevated neutrophils in NP tissue appear to exist in several subphenotypes that may play important pathogenic roles in CRSwNP.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 3","pages":"Pages 843-855"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620952","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":"Baseline epitope-specific IgE profiles are predictive of sustained unresponsiveness or high threshold 1-year post oral immunotherapy in the POISED trial","authors":"Maria Suprun PhD ,&nbsp;Ashley Sang Eun Lee MD ,&nbsp;Robert Getts PhD ,&nbsp;Simon Peck BS ,&nbsp;Sayantani B. Sindher MD ,&nbsp;Kari C. Nadeau MD, PhD ,&nbsp;R. Sharon Chinthrajah MD ,&nbsp;Stephen J. Galli MD ,&nbsp;Hugh A. Sampson MD","doi":"10.1016/j.jaci.2024.10.017","DOIUrl":"10.1016/j.jaci.2024.10.017","url":null,"abstract":"<div><h3>Background</h3><div>Results from the POISED trial suggest that discontinuation of peanut oral immunotherapy can increase the risk of regaining clinical reactivity to peanut.</div></div><div><h3>Objective</h3><div>We sought to determine whether patients who achieved sustained unresponsiveness (SU) or sustained high threshold (SHT) have different baseline sequential epitope-specific IgE profiles than patients who achieved transient desensitization.</div></div><div><h3>Methods</h3><div>Subjects in the POISED trial (NCT02103270) were randomized to peanut (n = 95) or placebo (n = 25) for 24 months. Oral immunotherapy–desensitized subjects were then assigned to no peanut (PN-0) (n = 51) or 300 mg peanut (PN-300) (n = 30) for 12 months. SU and SHT were determined by subjects in PN-0 and PN-300, respectively, passing 4000-mg peanut oral challenge. Specific IgE and IgG₄ levels to peanut; Ara h 1, Ara h 2, and Ara h 3 proteins; and 64 allergenic epitopes were measured. We developed machine learning models with bootstrap simulations using baseline data to predict SU/SHT.</div></div><div><h3>Results</h3><div>Of 80 (84%) subjects who were desensitized to peanut, 13% (n = 8) and 37% (n = 13) achieved SU/SHT in PN-0 and PN-300 groups. Decreases in epitope-and protein-specific IgE levels and increases in IgG₄ levels were observed during 2 years of oral immunotherapy. At baseline, patients with SU in PN-0, but not PN-300, group had lower epitope-specific IgE and protein-specific IgE levels compared with the transient desensitization group. A machine learning model with 12 baseline epitope-specific IgEs and age could predict SU/SHT with accuracy of 94%, area under the curve 0.97, sensitivity 1.00, and specificity 0.91.</div></div><div><h3>Conclusions</h3><div>Subjects who achieved SU/SHT had different baseline protein- and epitope-specific IgE profiles than subjects with transient desensitization. These profiles may help identify patients with an increased likelihood of achieving SU/SHT.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 3","pages":"Pages 923-931.e2"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590625","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":"MRGPRX2 facilitates IgE-mediated systemic anaphylaxis in a newly established knock-in mouse model","authors":"Maram Bawazir BDS ,&nbsp;Sangita Sutradhar PhD ,&nbsp;Saptarshi Roy PhD ,&nbsp;Hydar Ali PhD","doi":"10.1016/j.jaci.2024.11.021","DOIUrl":"10.1016/j.jaci.2024.11.021","url":null,"abstract":"<div><h3>Background</h3><div>In addition to FcεRI, a subtype of human mast cells (MCs) expresses Mas-related G protein–coupled receptor X2 (MRGPRX2; mouse counterpart MrgprB2). Although MrgprB2 contributes to IgE-mediated passive systemic anaphylaxis (PSA) <em>in vivo</em>, an MRGPRX2 inhibitor, compound 9 (C9), does not block MrgprB2- or IgE-mediated MC degranulation <em>in vitro</em>.</div></div><div><h3>Objective</h3><div>Our aim was to generate mice expressing human MRGPRX2 to study receptor function <em>in vitro</em> and PSA <em>in vivo</em>.</div></div><div><h3>Methods</h3><div>The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated gene editing approach was utilized to replace endogenous MrgprB2 with human MRGPRX2 in mice (MRGPRX2-KI mice). MRGPRX2 expression in the skin, gingiva, trachea, and colon were evaluated by using an anti-human MRGPRX2 antibody. Peritoneal MCs (PMCs) cultured from wild-type, MRGPRX2-KI, and MrgprB2^−/− mice were used to study agonists-induced degranulation. The effects of selective MRGPRX2 inhibitors (C9 and compound 9-6 [C9-6]) on substance P– or IgE-mediated MC degranulation <em>in vitro</em> and IgE-mediated PSA <em>in vivo</em> were tested.</div></div><div><h3>Results</h3><div>MRGPRX2-expressing MCs were present in tissues of MRGPRX2-KI mice. Most of the agonists tested induced greater degranulation at lower concentrations in PMCs from MRGPRX2-KI mice than in cells from wild-type mice. Furthermore, C9 and C9-6 inhibited degranulation in MRGPRX2-KI PMCs in response to substance P. In contrast, they had no effect on IgE-mediated degranulation <em>in vitro</em> but did inhibit PSA in MRGPRX2-KI mice <em>in vivo</em>.</div></div><div><h3>Conclusions</h3><div>MRGPRX2-KI mice provide a readily available source of primary MCs for signaling studies. Furthermore, transactivation of MRGPRX2 contributes to IgE-mediated PSA, suggesting that MRGPRX2-KI mice could be utilized as a preclinical model for testing novel therapeutics targeting MRGPRX2 and its cross talk with FcεRI.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 3","pages":"Pages 974-987.e1"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710270","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":"Leptin augments IL-13–induced airway eotaxins and submucosal eosinophilia in obesity-associated asthma","authors":"Jennifer L. Ingram PhD ,&nbsp;Victoria L. McQuade MRes ,&nbsp;Jasmine Weiss MD, MHS ,&nbsp;Jack T. Womble BS ,&nbsp;Mark D. Ihrie PhD ,&nbsp;Karen Zhao BS ,&nbsp;Dave Francisco BS ,&nbsp;Barbara Theriot MS ,&nbsp;Katelynn May BSN ,&nbsp;Haein Kim BS ,&nbsp;Matthew McCravy MD ,&nbsp;Maor Sauler MD ,&nbsp;Njira L. Lugogo MD ,&nbsp;Mary E. Sunday MD, PhD ,&nbsp;Jeffrey Everitt DVM ,&nbsp;Julia K.L. Walker PhD ,&nbsp;Robert M. Tighe MD ,&nbsp;Monica Kraft MD ,&nbsp;Loretta G. Que MD","doi":"10.1016/j.jaci.2024.10.039","DOIUrl":"10.1016/j.jaci.2024.10.039","url":null,"abstract":"<div><h3>Background</h3><div>Airway tissue eosinophilia can be an observed feature of obesity-associated type 2 (T2) asthma, but the processes mediating this inflammation are unknown.</div></div><div><h3>Objective</h3><div>To investigate a process whereby leptin, an adipokine elevated in obesity, potentiates pulmonary eosinophilia and eotaxin production by airway fibroblasts in T2 asthma.</div></div><div><h3>Methods</h3><div>We assessed associations between body mass index and airway eosinophilia as well as leptin and eotaxin production in 82 participants with asthma, 37 of whom exhibited obesity. Cultured human airway fibroblasts and mouse models of chronic allergic airway disease were used to evaluate leptin’s effect on eotaxin production and lung eosinophilia. The role of IL-13 receptor alpha 2 (IL-13Rα2) in mediating these processes was examined using specific neutralizing antibodies <em>in vitro</em>.</div></div><div><h3>Results</h3><div>In participants with T2 asthma and obesity, we observed that airway tissue eosinophilia did not associate with traditional T2 inflammation metrics such as peripheral and/or bronchoalveolar lavage fluid eosinophil counts or with fractional exhaled nitric oxide. Alternatively, we observed elevated bronchoalveolar lavage fluid leptin and eotaxin-1 levels. In airway fibroblasts from participants with asthma, leptin augmented IL-13–induced eotaxin-1 and eotaxin-3 production and <em>IL13RA2</em> expression. In mice, elevated leptin promoted airway IL-13Rα2 and eotaxin production by lung fibroblasts and lung tissue eosinophilia following chronic house dust mite allergen exposure. Inhibition of IL-13Rα2 reduced combined leptin and IL-13–stimulated eotaxin secretion by human airway fibroblasts.</div></div><div><h3>Conclusions</h3><div>We identified a potential association explaining airway tissue eosinophil retention in obesity-associated T2 asthma through leptin-mediated enhancement of IL-13–induced eosinophil chemokine production by airway fibroblasts, a process requiring IL-13Rα2.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 3","pages":"Pages 819-833.e10"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710263","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":"Somatic mosaicism in genetic errors of immunity","authors":"Megan A. Cooper MD, PhD","doi":"10.1016/j.jaci.2024.11.038","DOIUrl":"10.1016/j.jaci.2024.11.038","url":null,"abstract":"<div><div>Genetic mosaicism in somatic cells can lead to the presence of pathogenic variants in a subset of immune cells causing genetic errors of immunity, often phenocopying germline inborn errors of immunity. Over the last 2 decades, significant progress has been made in the identification of these disorders in patients, including discovery of new diseases. Diagnosis of disease-causing somatic mosaicism provides a target for treatment and monitoring of patients and has implications for genetic counseling. However, there continue to be barriers in the identification of somatic mosaicism, particularly for the clinical diagnosis of patients, based on the limitations of current diagnostic sequencing and analysis approaches. This review focuses on how somatic mosaicism can lead to genetic errors of immunity, the genes known to be associated with somatic genetic errors of immunity, and challenges in the field for accurate diagnosis of patients.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 3","pages":"Pages 759-767"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887520","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}