Journal of Allergy and Clinical Immunology最新文献

{"title":"Long-term durability between parent and child patient-reported outcomes in eosinophilic esophagitis","authors":"Lisa J. Martin PhD ,&nbsp;Xue Zhang PhD ,&nbsp;Mirna Chehade MD ,&nbsp;Carla M. Davis MD ,&nbsp;Evan S. Dellon MD, MPH ,&nbsp;Gary W. Falk MD ,&nbsp;Sandeep K. Gupta MD ,&nbsp;Ikuo Hirano MD ,&nbsp;Girish S. Hiremath MD ,&nbsp;David A. Katzka MD ,&nbsp;Paneez Khoury MD ,&nbsp;John Leung MD ,&nbsp;Paul Menard-Katcher MD ,&nbsp;Nirmala Gonsalves MD ,&nbsp;Robert D. Pesek MD ,&nbsp;Jonathan M. Spergel MD, PhD ,&nbsp;Joshua B. Wechsler MD ,&nbsp;Kara Kliewer PhD ,&nbsp;Nicoleta C. Arva MD ,&nbsp;Margaret H. Collins MD ,&nbsp;Seema S. Aceves MD, PhD","doi":"10.1016/j.jaci.2024.07.011","DOIUrl":"10.1016/j.jaci.2024.07.011","url":null,"abstract":"<div><h3>Background</h3><div>Because young children cannot self-report symptoms, there is a need for parent surrogate reports. Although early work suggested parent-child alignment for eosinophil esophagitis (EoE) patient-reported outcomes (PROs), the longitudinal alignment is unclear.</div></div><div><h3>Objective</h3><div>We sought to assess the agreement and longitudinal stability of PROs between children with EoE and their parents.</div></div><div><h3>Methods</h3><div>A total of 292 parent-child respondents completed 723 questionnaires over 5 years in an observational trial in the Consortium of Eosinophilic Gastrointestinal Disease Researchers. The change in and agreement between parent and child Pediatric Eosinophilic Esophagitis Symptom Score version 2 (PEESSv2.0) and Pediatric Quality of Life Eosinophilic Esophagitis Module (PedsQL-EoE) PROs over time were assessed using Pearson correlation and Bland-Altman analyses. Clinical factors influencing PROs and their agreement were evaluated using linear mixed models.</div></div><div><h3>Results</h3><div>The cohort had a median disease duration equaling 3.7 years and was predominantly male (73.6%) and White (85.3%). Child and parent PEESSv2.0 response groups were identified and were stable over time. There was strong correlation between child and parent reports (PEESSv2.0, 0.83;PedsQL-EoE, 0.74), with minimal pairwise differences for symptoms. Longitudinally, parent-reported PedsQL-EoE scores were stable (<em>P</em> ≥ .32), whereas child-reported PedsQL-EoE scores improved (<em>P</em> = .026). A larger difference in parent and child PedsQL-EoE reports was associated with younger age (<em>P</em> &lt; .001), and differences were driven by psychosocial PRO domains.</div></div><div><h3>Conclusions</h3><div>There is strong longitudinal alignment between child and parent reports using EoE PROs. These data provide evidence that parent report is a stable proxy for objective EoE symptoms in their children.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"154 5","pages":"Pages 1232-1240.e12"},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141766200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world effectiveness of dupilumab in a European cohort of CRSwNP (CHRINOSOR).","authors":"Sven F Seys, Sven Schneider, Joost de Kinderen, Sietze Reitsma, Carlo Cavaliere, Peter-Valentin Tomazic, Christina Morgenstern, Geoffrey Mortuaire, Martin Wagenmann, Giulia Bettio, Andrea Ciofalo, Zuzana Diamant, Julia Eckl-Dorna, Wytske J Fokkens, Clemens Holzmeister, Gert Mariën, Simonetta Masieri, Josje Otten, Kathrin Scheckenbach, Aldine Tu, Claus Bachert","doi":"10.1016/j.jaci.2024.10.016","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.016","url":null,"abstract":"<p><strong>Background: </strong>Pivotal studies with dupilumab demonstrated clinically relevant improvements in nasal polyp score (NPS), symptom and quality of life scores in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).</p><p><strong>Objective: </strong>We evaluated the effectiveness of dupilumab in a large-scale CRSwNP cohort from 6 European tertiary care centres.</p><p><strong>Methodology: </strong>NPS, SinoNasal Outcome Test (SNOT)-22 score, visual analogue scale (VAS) for total sinus symptoms, loss of smell (LoS) and nasal blockage (NB), and Asthma Control Test (ACT) score were collected from hospital records and assessed at baseline, 24 and 52 weeks of treatment of dupilumab in CRSwNP patients. Treatment effectiveness was evaluated in relation to demographic and lifestyle factors, sinus surgery history, presence of comorbidities and blood eosinophil counts (BEC). Treatment response was evaluated according to EUFOREA 2021 criteria.</p><p><strong>Results: </strong>All patient outcomes improved at 24 and 52 weeks of treatment compared to baseline. Dupilumab showed effectiveness independent of age, sex, body mass index, smoking status, prior sinus surgery, presence of asthma, NSAID exacerbated respiratory disease (NERD), allergy or baseline BEC. 92.5% and 94.4% showed an improvement in at least 1 EUFOREA criterion at 24 and 52 weeks respectively. 54.4% and 68.2% reached all 4 of the more stringent EUFOREA criteria at 24 and 52 weeks respectively.</p><p><strong>Conclusions: </strong>Real-world evaluation of dupilumab effectiveness demonstrates a robust and sustained response in at least two thirds of patients at 52 weeks of treatment. Favourable treatment response was independent of the number of sinus surgery procedures, major comorbidities or baseline systemic levels of type 2 inflammation.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564495","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":"Sensory neuroimmune signaling in the pathogenesis of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN).","authors":"Xiaobao Huang, Suiting Ao, Rui Xu, Xuemei Gao, Shiling Qi, Yarong Liang, Peiying Feng, Ruzeng Xue, Yingying Ren, Jiande Han, Fengxian Li, Coco Chu, Fang Wang","doi":"10.1016/j.jaci.2024.10.015","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.015","url":null,"abstract":"<p><strong>Background: </strong>Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening cutaneous reactions often triggered by medications. While the involvement of CD8⁺ T cells causing keratinocyte death is well recognized, the contribution of neural elements to the persistent skin inflammation has been largely overlooked.</p><p><strong>Objective: </strong>To investigate the potential neuroimmune regulation in SJS/TEN.</p><p><strong>Methods: </strong>Unbiased single-cell RNA sequencing and flow cytometry were performed using circulating CD8⁺ T cells from healthy controls and patients with SJS/TEN. ELISA and LEGENDplex assays were respectively used to detect neuropeptides and inflammatory mediators. Skin tissues were examined by immunofluorescence staining for neuropeptide-associated nerves and cytokine receptors. Calcium imaging, Smart-seq, and a 3D skin model were employed for cultured human CD8⁺ T cells.</p><p><strong>Results: </strong>The unbiased RNA-sequencing revealed an upregulation of the receptor for neuropeptide calcitonin gene-related peptide (CGRP), known as RAMP1, in effector CD8⁺ T cells in SJS/TEN. Increased CGRP⁺ nerve fibers and CGRP levels, along with upregulated IL-15R and IL-18R on CD8⁺ T cells, were displayed in the affected skin of SJS/TEN. The CGRP-RAMP1 axis was necessary and sufficient to enhance receptors for IL-15 and IL-18 and cytotoxic activities in CD8⁺ T cells, ultimately resulting in keratinocyte apoptosis. Calcium influx was detected in CGRP-stimulated CD8⁺ T cells. HCN2, a hyperpolarization-activated cation channel, was required for this process and the subsequent cytotoxic effects.</p><p><strong>Conclusions: </strong>Our study highlights the role of neural elements in regulating CD8⁺ T cell-mediated inflammatory responses and provides new potential translational targets to improve the outcomes of severe cutaneous drug reactions.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557789","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":"Eosinophil extracellular traps drive T follicular helper cell differentiation via VIRMA-dependent MAF stabilization in bullous pemphigoid.","authors":"Shengxian Shen, Hui Fang, Xia Li, Yifan Zhou, Xin Tang, Haijun Miao, Liang Li, Jiaoling Chen, Ke Xue, Chen Zhang, Mengyang Chu, Bingyu Pang, Yaxing Bai, Hongjiang Qiao, Erle Dang, Shuai Shao, Gang Wang","doi":"10.1016/j.jaci.2024.09.030","DOIUrl":"10.1016/j.jaci.2024.09.030","url":null,"abstract":"<p><strong>Background: </strong>Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by the presence of pathogenic autoantibodies and a substantial influx of immune cells into skin lesions. However, the role of eosinophils in BP remains inadequately elucidated.</p><p><strong>Objective: </strong>We sought to determine the pathologic involvement of eosinophils and eosinophil extracellular traps (EETs) in BP.</p><p><strong>Methods: </strong>Human samples collected from BP patients and healthy controls were utilized to explore the potential role of eosinophils and their EETs in BP patients through serologic detection, flow cytometry, and immunofluorescence. Naive CD4⁺ T cells isolated from healthy donors were stimulated and subjected to further analysis via RNA sequencing. We additionally evaluated the potential of targeting EETs in BP180-immunized BP-like mice and in in vitro settings.</p><p><strong>Results: </strong>We found that elevated levels of eosinophils and EETs in BP patients correlated with disease severity. The DNA components within EETs played a crucial role in driving the differentiation of naive CD4⁺ T cells into follicular helper T (Tfh) cells by activating coil domains containing 25 (CCDC25). Treatment with DNase I, which disrupts the structural integrity of EETs, or neutralizing antibody against CCDC25 reduced the expansion of Tfh cells and suppressed the production of autoantibodies in BP180-immunized BP-like mouse models. Additionally, we discovered that EETs induced the N⁶-methyladenosine methylation of the transcription factor musculoaponeurotic fibrosarcoma (MAF) via the DNA-CCDC25-VIRMA pathway, thereby enhancing its mRNA stability and promoting Tfh cell differentiation.</p><p><strong>Conclusion: </strong>Our study revealed a previously unrecognized mechanism by which EETs trigger abnormal Tfh cell differentiation through CCDC25, followed by Vir-like m⁶A methyltransferase-associated protein (VIRMA)-mediated N⁶-methyladenosine modification of MAF. These insights provide promising avenues for the development of targeted therapeutic interventions in the field of BP and potentially other autoimmune diseases.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567337","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":"Inborn errors of immunity are associated with increased COVID-19-related hospitalization and intensive care compared to the general population.","authors":"Hannes Lindahl,Fredrik Kahn,Åsa Nilsdotter-Augustinsson,Mats Fredrikson,Pontus Hedberg,Isabela Killander Möller,Lotta Hansson,Lisa Blixt,Sandra Eketorp Sylvan,Anders Österborg,Soo Aleman,Christina Carlander,Sofia Nyström,Peter Bergman","doi":"10.1016/j.jaci.2024.10.013","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.013","url":null,"abstract":"BACKGROUNDIt is thought that patients with inborn errors of immunity (IEI) are more susceptible to severe Covid-19 than the general population, but a quantification of this potential risk is largely missing.OBJECTIVETo assess the impact of Covid-19 on patients with IEI.METHODSA nationwide cohort study was performed to estimate the relative risk (RR) for hospitalization, intensive care, and death within 30 days after a positive SARS-CoV-2 test in an IEI population (n=2392) compared to the general population (n=8,270,705) using data from Swedish national registries. Three time-periods were studied: Pre-vaccination, Alpha/Delta, and Omicron. Adjustment was made for demographics, income, comorbidities, and vaccination status.RESULTSDuring the Pre-vaccination period 25.2% of the IEI population were hospitalized, compared to 17.5% and 5.2% during the Alpha/Delta and Omicron periods, respectively. For the three time periods the adjusted RR for hospitalization in the IEI population compared to the general population was 3.1 [95% CI 2.1-4.2], 3.5 [2.4-4.8], and 4.3 [2.5-6.7], respectively. The adjusted RR for intensive care after Covid-19 were 5.6 [2.6-10.8], 4.7 [1.7-10.1], and 4.7 [1.7-10.1] for the three periods. Five patients (0.6%) in the IEI population died within 30 days of a positive PCR test compared to 18,773 (0.2%) in the general population during the three study periods.CONCLUSIONPatients with IEI had 3-4 times higher risk for hospitalization and 5 times higher risk for intensive care during Covid-19, compared to the general population.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"24 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490443","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":"Defining the overlap between asthma and bronchiectasis: A call for consensus definition.","authors":"Sang Hyuk Kim, Bumhee Yang, Kyung Hoon Min, Hyun Lee","doi":"10.1016/j.jaci.2024.05.033","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.05.033","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466077","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":"Atopic dermatitis, food allergy, anaphylaxis, other atopic conditions.","authors":"Michelle L Hernandez, Pedro Giavina Bianchi, Richard Lockey, Sarita U Patil","doi":"10.1016/j.jaci.2024.10.011","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.011","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466076","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":"Thymic inborn errors of immunity.","authors":"Francesca Pala, Luigi D Notarangelo, Michail S Lionakis","doi":"10.1016/j.jaci.2024.10.009","DOIUrl":"10.1016/j.jaci.2024.10.009","url":null,"abstract":"<p><p>The thymus is crucial for optimal T-cell development by facilitating the generation and selection of a diverse repertoire of T cells that can recognize foreign antigens while promoting tolerance to self-antigens. A number of inborn errors of immunity causing complete or partial defects in thymic development (athymia) and/or impaired thymic function have been increasingly recognized that manifest clinically with a combination of life-threatening infections, severe multiorgan autoimmunity, and/or cardiac, craniofacial, ectodermal, and endocrine abnormalities. The introduction of newborn screening programs and the advent of thymic transplantation show promise for early detection and improving the outcomes of patients with certain thymic inborn errors of immunity. We discuss our current understanding of the genetics, immunopathogenesis, diagnosis, and treatment of inborn errors of immunity that impair thymic development and/or function.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466079","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":"Evolution of the concept of immune dysregulation and current classification.","authors":"Sarah E Henrickson","doi":"10.1016/j.jaci.2024.10.010","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.010","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466078","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":"Evolution of the concept of immune dysregulation and current classification.","authors":"Sarah E Henrickson","doi":"10.1016/j.jaci.2024.10.010","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.010","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"75 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486315","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}