Journal of Allergy and Clinical Immunology最新文献

{"title":"Melatonin treatment increases skin microbiota-derived propionic acid to alleviate atopic dermatitis","authors":"Lan Yang PhD ,&nbsp;Piao Wang BS ,&nbsp;Ting Gao MD, PhD ,&nbsp;Xinyu Huang BS ,&nbsp;Zhen Lin MS ,&nbsp;Evan Sweren BS ,&nbsp;Yue Li BS ,&nbsp;Lu Chen BS ,&nbsp;Martin P. Alphonse PhD ,&nbsp;Jianglin Zhang MD, PhD ,&nbsp;Gaofeng Wang MD, PhD","doi":"10.1016/j.jaci.2024.11.019","DOIUrl":"10.1016/j.jaci.2024.11.019","url":null,"abstract":"<div><h3>Background</h3><div>Melatonin has been reported to relieve the inflammatory symptoms and improve sleep disturbance in patients with atopic dermatitis (AD). Recent studies showed that melatonin produced beneficial effects by remodeling intestinal microbiota composition; however, whether the beneficial effects of melatonin in AD were mediated by the modulation of skin microbiota remains unclear.</div></div><div><h3>Objective</h3><div>We sought to investigate the mechanism by which melatonin treatment–induced changes in the skin microbiota composition further alleviated AD.</div></div><div><h3>Methods</h3><div>The changes in skin bacterial composition after melatonin treatment were detected by 16S-rRNA sequencing. Further mechanisms were explored in calcipotriol (MC903)-induced AD mice and HaCaT cells through skin microbiota transplantation, quantification detection of short-chain fatty acids, transcriptome and single-cell sequencing analysis, quantitative RT-PCR, Western blotting, and Cell Counting Kit-8 assay.</div></div><div><h3>Results</h3><div>We demonstrated that melatonin reshaped the skin microbiota in AD mice. The transplantation of skin microbiota from melatonin-treated mice alleviated AD symptoms in mice. Skin microbiota–derived short-chain fatty acids, especially propionic acid, were increased in the skin of melatonin-treated AD mice, which further inhibited FABP5 expression to alleviate AD. Propionic acid also inhibited FABP5 expression in HaCaT cells, which was reversed by the treatment of GPR43 inhibitor GLPG0974. GLPG0974 also blocked the therapeutic effects of melatonin on AD mice.</div></div><div><h3>Conclusions</h3><div>Our study demonstrated that melatonin alleviates AD through the skin microbiota/propionic acid/GPR43/FABP5 axis, highlighting a novel role of melatonin as a modulator of skin microbiota to alleviate AD.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 3","pages":"Pages 880-891.e9"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695527","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":"Splice site and de novo variants can cause PLCG2-associated immune dysregulation with cold urticaria","authors":"Sophia R. Chou BA ,&nbsp;Alexis C. Bailey MD ,&nbsp;Kathleen Baysac PhD ,&nbsp;Andrew J. Oler PhD ,&nbsp;Joshua D. Milner MD ,&nbsp;Michael J. Ombrello MD","doi":"10.1016/j.jaci.2024.06.025","DOIUrl":"10.1016/j.jaci.2024.06.025","url":null,"abstract":"<div><h3>Background</h3><div>Phospholipase Cγ2 (PLCγ2) is an important signaling molecule that receives and transmits signals from various cell surface receptors in most hematopoietic lineages. Variants of <em>PLCG2</em> cause PLCγ2-associated immune dysregulation (PLAID), a family of conditions classified by mutational effect. PLAID with cold urticaria (PLAID-CU) is caused by in-frame deletions of <em>PLCG2</em> that are dominant negative at physiologic temperatures but become spontaneously active at subphysiologic temperatures.</div></div><div><h3>Objective</h3><div>We identified genetic lesions that cause PLAID by combining RNA sequencing of full-length <em>PLCG2</em> with whole genome sequencing.</div></div><div><h3>Methods</h3><div>We studied 9 probands with antibody deficiency and a positive evaporative cooling test, along with 2 known PLAID-CU patients and 3 healthy subjects. Illumina sequencing was performed on full-length <em>PLCG2</em> cDNA synthesized from peripheral blood mononuclear cell RNA, and whole genome sequencing was used to identify genetic lesions. Novel alternate transcripts were overexpressed in the <em>Plcg2-</em>deficient DT40 cell overexpression system. Extracellular signal-regulated kinase (ERK) phosphorylation was quantified by flow cytometry with and without B-cell receptor crosslinking.</div></div><div><h3>Results</h3><div>Two probands expressed novel alternative transcripts of <em>PLCG2</em> with in-frame deletions. Proband 1, expressing <em>PLCG2</em> without exons 18-19, carried a splice site mutation in intron 19. Proband 2, expressing <em>PLCG2</em> without exons 19-22, carried a 14 kb <em>de novo</em> deletion of <em>PLCG2.</em> DT40 cells overexpressing the exon 18-19 or exon 19-22 deletions failed to phosphorylate ERK in response to B-cell receptor crosslinking.</div></div><div><h3>Conclusion</h3><div>In addition to autosomal dominant genomic deletions, <em>de novo</em> deletions and splice site mutations of <em>PLCG2</em> can also cause PLAID-CU. All of these can be identified by cDNA-based sequencing.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 3","pages":"Pages 1045-1049.e4"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817884","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":"Update on inborn errors of immunity","authors":"Hanna IJspeert PhD ,&nbsp;Emily S.J. Edwards PhD ,&nbsp;Robyn E. O’Hehir MD, PhD ,&nbsp;Virgil A.S.H. Dalm MD, PhD ,&nbsp;Menno C. van Zelm PhD","doi":"10.1016/j.jaci.2024.12.1075","DOIUrl":"10.1016/j.jaci.2024.12.1075","url":null,"abstract":"<div><div>Ever since the first description of an inherited immunodeficiency in 1952 in a boy with gammaglobulin deficiency, new insights have progressed rapidly in disorders that are now referred to as inborn errors of immunity. In a field where fundamental molecular biology, genetics, immune signaling, and clinical care are tightly intertwined, 2022-24 saw a multitude of advances. Here we report a selection of research updates with a main focus on (1) diagnosis and screening, (2) new genetic defects, (3) susceptibility to severe coronavirus disease 2019 infection and impact of vaccination, and (4) treatment. Importantly, new pathogenic insights more rapidly affect treatment outcomes, either through an earlier and more precise diagnosis or through implementation of novel, personalized treatment. The field is growing rapidly, so awareness, communication, and collaboration are key to improving treatment outcomes.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 3","pages":"Pages 740-751"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Special Thank-You to Our Reviewers","authors":"","doi":"10.1016/S0091-6749(25)00101-0","DOIUrl":"10.1016/S0091-6749(25)00101-0","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 3","pages":"Pages 754-758"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519082","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":"Examining disparities in biologic therapy initiation: The intersection of race/ethnicity and insurance type","authors":"Khamron Micheals PhD, MHA, RRT ,&nbsp;Darlene Bhavnani PhD, MPH ,&nbsp;Elizabeth C. Matsui MD, MHS","doi":"10.1016/j.jaci.2025.01.002","DOIUrl":"10.1016/j.jaci.2025.01.002","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 3","pages":"Pages 810-812"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989382","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 2024 Nobel Prizes: AI and computational science take center stage","authors":"Nicholas L. Rider DO ,&nbsp;Mohamed Shamji MSc, PhD. FAAAAI","doi":"10.1016/j.jaci.2024.11.040","DOIUrl":"10.1016/j.jaci.2024.11.040","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 3","pages":"Pages 808-809"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970835","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":"Role of DOCK8 in cytokine storm syndromes","authors":"Mingce Zhang MD, PhD ,&nbsp;Remy R. Cron ,&nbsp;Niansheng Chu MD ,&nbsp;Junior Nguyen BS ,&nbsp;Scott M. Gordon MD, PhD ,&nbsp;Esraa M. Eloseily MD, MSc ,&nbsp;T. Prescott Atkinson MD, PhD ,&nbsp;Peter Weiser MD ,&nbsp;Mark R. Walter PhD ,&nbsp;Portia A. Kreiger MD ,&nbsp;Scott W. Canna MD ,&nbsp;Edward M. Behrens MD ,&nbsp;Randy Q. Cron MD, PhD","doi":"10.1016/j.jaci.2024.10.004","DOIUrl":"10.1016/j.jaci.2024.10.004","url":null,"abstract":"<div><h3>Background</h3><div>Cytokine storm syndromes (CSSs), including hemophagocytic lymphohistiocytosis (HLH), are increasingly recognized as hyperinflammatory states leading to multiorgan failure and death. Familial HLH in infancy results from homozygous genetic defects in perforin-mediated cytolysis by CD8 T lymphocytes and natural killer (NK) cells. Later-onset CSSs are often associated with heterozygous defects in familial HLH genes, but genetic etiologies for most are unknown. We identified rare dedicator of cytokinesis 8 (<em>DOCK8</em>) variants in patients with CSS.</div></div><div><h3>Objective</h3><div>We sought to explore the role of CSS patient–derived <em>DOCK8</em> mutations on cytolytic activity in NK cells and to further study effects of <em>DOCK8</em> deficiency in murine models of CSSs.</div></div><div><h3>Methods</h3><div><em>DOCK8</em> cDNAs from 2 unrelated patients with CSS with different missense mutations were introduced into human NK-92 cells by foamy virus transduction. NK-cell degranulation (CD107a), cytolytic activity against K562 target cells, and IFN-γ production were explored by flow cytometry. A third patient with CSS with <em>DOCK8</em> mRNA splice acceptor site variant was explored by exon trapping. <em>Dock8</em>^{<em>−/−</em>} mice were assessed for features of CSS (weight loss, splenomegaly, hepatic inflammation, cytopenias, and IFN-γ levels) on challenge with lymphocytic choriomeningitis virus and excess IL-18.</div></div><div><h3>Results</h3><div>Both patient <em>DOCK8</em> missense mutations decreased cytolytic function in NK cells in a partial dominant-negative fashion <em>in vitro</em>. The patient <em>DOCK8</em> splice variant disrupted mRNA splicing <em>in vitro</em>. Lymphocytic choriomeningitis virus infection promoted CSS in <em>Dock8</em>^{<em>−/−</em>} mice and interacted with excess IL-18, limiting T-cell numbers while promoting CD8 T-cell hyperactivation.</div></div><div><h3>Conclusions</h3><div>Mutations in <em>DOCK8</em> may contribute to CSS-like hyperinflammatory states by altering cytolytic function in a threshold model of disease.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 3","pages":"Pages 1015-1026.e5"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451422","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":"Importance of mast cell histamine secretion in IgG-mediated systemic anaphylaxis","authors":"Marat V. Khodoun DVM, PhD ,&nbsp;Richard T. Strait MD ,&nbsp;Ashley Hall BS ,&nbsp;Adrienne Stolfi PhD ,&nbsp;Fred D. Finkelman MD","doi":"10.1016/j.jaci.2024.11.009","DOIUrl":"10.1016/j.jaci.2024.11.009","url":null,"abstract":"<div><h3>Background</h3><div>IgG can mediate murine and human systemic anaphylaxis (SA). The roles of mast cells (MCs) and histamine in IgG-mediated anaphylaxis are controversial for mice and have not been studied <em>in vivo</em> for humans. We are now investigating these issues.</div></div><div><h3>Methods</h3><div>Actively or passively sensitized wild-type and immune-deficient mice were induced to develop anaphylaxis by intravenous antigen challenge. Anaphylaxis was characterized by evaluating hypothermia, hypomobility, histamine, and MC protease responses.</div></div><div><h3>Results</h3><div>In contrast to our previous results with protein-immunized mice from a conventional colony, IgG-mediated passive SA in our specific pathogen-free colony mice depended considerably on histamine produced by connective tissue MCs (CTMCs) in response to FcγRIII crosslinking. This was found for C57BL/6 and young male and female BALB/c mice, including BALB/c mice newly arrived from 3 vendors. IgG-mediated anaphylaxis was less histamine dependent in old than young mice. Although both mucosal MC (MMC) and CTMC responses were severely depleted in c-kit–deficient mice, MMC responses depended considerably more than CTMC responses on c-kit for maintenance. In immunologically naive mice, FcγRIII crosslinking strongly activated a subset of CTMCs but had little ability to activate MMCs. <em>In vivo</em> LPS + poly I:C treatment decreased histamine dependence of IgG-mediated anaphylaxis, while a strong T_H2 immune response increased FcγRIII crosslinking-induced MMC activation. IgG-mediated activation of human MCs in reconstituted immunodeficient mice induced histamine-dependent anaphylaxis.</div></div><div><h3>Conclusion</h3><div>IgG-dependent SA can be mediated largely by histamine released by mouse CTMCs and human MCs; histamine dependence is influenced by mouse age, sex, and immune and infectious history, as well as the anaphylaxis model studied.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 3","pages":"Pages 956-973"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644188","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":"Effects of dupilumab on mannitol airway hyperresponsiveness in uncontrolled severe asthma","authors":"Kirsten E. Stewart MBChB ,&nbsp;Chris RuiWen Kuo MD ,&nbsp;Rory Chan PhD ,&nbsp;Brian J. Lipworth MD","doi":"10.1016/j.jaci.2024.11.024","DOIUrl":"10.1016/j.jaci.2024.11.024","url":null,"abstract":"<div><h3>Background</h3><div>Airway hyperresponsiveness (AHR) is a hallmark of persistent asthma. However, effects of IL-4/13 blockade with dupilumab (Dupi) on AHR are unknown.</div></div><div><h3>Objectives</h3><div>This study sought to investigate the effect of 12 weeks of Dupi on AHR, asthma control, and quality of life.</div></div><div><h3>Methods</h3><div>After a 4-week run-in on beclomethasone/formoterol maintenance and reliever therapy (baseline), participants with uncontrolled type-2 high severe asthma received open-label Dupi 300 mg twice weekly, for 12 weeks. Mannitol challenges were done at baseline, 2, 4, and 12 weeks and following a 12-week washout. Study power was 90% to detect 1 doubling difference (dd) in mannitol PD₁₀ FEV₁ threshold at week 12.</div></div><div><h3>Results</h3><div>Of 24 enrolled patients, 23 completed per protocol mannitol AHR at 12 weeks. Mean baseline values were age 52 years, FEV₁ 82%, Asthma Control Questionnaire 2.53, mini–Asthma Quality of Life Questionnaire 3.84, inhaled corticosteroids dose 1300 μg; fractional exhaled nitric oxide 50 parts per billion; Eosinophils 552 cells/μL. Mannitol sensitivity as PD₁₀ was significantly attenuated by week 4, and reactivity as response dose ratio by week 2. After 12 weeks of Dupi, mean dd for PD₁₀ was 1.78 (95% CI: 1.23-2.33; <em>P</em> &lt; .001) and for response dose ratio was 3.40 (95% CI: 2.25-4.55; <em>P</em> &lt; .001). At week 12, Asthma Control Questionnaire improved by 1.73 (95% CI: 1.11-2.36; <em>P</em> &lt; .001); mini–Asthma Quality of Life Questionnaire by 2.31 (95% CI: 1.57-3.05; <em>P</em> &lt; .001); FEV₁ by 0.39 L (95% CI: 0.11-0.67; <em>P</em> &lt; .01); and PEF by 61 L/min (95% CI: 24-98; <em>P</em> &lt; .001). Beclomethasone/formoterol maintenance and reliever therapy requirement was reduced at 12 weeks versus baseline by 1.7 puffs/d (95% CI: 0.7–2.7; <em>P</em> &lt; .01). After washout at week 24, the dd change was 0.96 (95% CI: 0.02-1.91; <em>P</em> &lt; .05).</div></div><div><h3>Conclusions</h3><div>Dupilumab attenuated mannitol AHR to a clinically relevant degree despite concomitant inhaled corticosteroid reduction, combined with improvements in lung function, asthma control, and quality of life.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 3","pages":"Pages 834-842.e6"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NLRC4-associated autoinflammatory disease: Insights from mouse models and somatic variants","authors":"Mathijs Willemsen MD, PhD ,&nbsp;Willem Roosens MD ,&nbsp;Frederik Staels MD, PhD ,&nbsp;Thea H.M. Schoonbrood MD ,&nbsp;Rik Schrijvers MD, PhD","doi":"10.1016/j.jaci.2024.12.1076","DOIUrl":"10.1016/j.jaci.2024.12.1076","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 3","pages":"Pages 803-807"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887523","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}