Journal of Allergy and Clinical Immunology最新文献

{"title":"New insights into the endotypes of chronic rhinosinusitis in the biologic era.","authors":"Ming Wang, Ying Li, Jingyun Li, Bing Yan, Chengshuo Wang, Luo Zhang, Feng Lan","doi":"10.1016/j.jaci.2025.02.015","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.015","url":null,"abstract":"<p><p>Chronic rhinosinusitis (CRS) exhibits significant heterogeneity and has been generally classified as Type 1 (T1), T2, and T3 endotypes according to the histopathological and inflammatory features of the nasal mucosa. T2 inflammation has been regarded as the predominant endotype of CRS linked to disease severity and refractory conditions. The development of biological agents that specifically target key molecules involved in T2 inflammation offers a highly effective and promising therapeutic approach for CRS. Recent findings have expanded the understanding of CRS endotypes by incorporating a range of disease-related molecules for classification, with progress made on the endotyping of CRS without nasal polyps. In addition, there has been an increasing emphasis on the study of mixed inflammatory endotypes. This review examines recent findings on CRS endotyping and the related non-invasive biomarkers, as well as novel mechanisms governing endotype formation, and the efficacy of biologics in targeting T2 inflammation. Further research is warranted to understand if newly identified CRS endotypes show clinical significance for precision medicine and the management and treatment of refractory CRS in the era of biologics.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476641","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":"Molecular mimicry-driven autoimmunity in chronic rhinosinusitis with nasal polyps.","authors":"Tomoaki Asamori, Hiroto Katoh, Mikiya Takata, Daisuke Komura, Miwako Kakiuchi, Itaru Hashimoto, Madoka Sakurai, Asami Yamamoto, Takeshi Tsutsumi, Takahiro Asakage, Yasushi Ota, Shumpei Ishikawa","doi":"10.1016/j.jaci.2025.02.014","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.014","url":null,"abstract":"<p><strong>Background: </strong>The pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) remains a subject of discussion. Although both microbial infection and autoimmunity have been proposed as potential contributors to CRSwNP pathobiology, their respective roles and intricate interactions in disease progression remain unclear owing to the limited knowledge regarding dysregulated humoral immunity in CRSwNP.</p><p><strong>Objective: </strong>To deepen our understanding of CRSwNP, we sought to identify the precise humoral antigens targeted by dominant B-cell clones within the disease environments.</p><p><strong>Methods: </strong>Immunoglobulin repertoire sequencing was performed to identify dominant B-cell clones in CRSwNP tissues. These immunoglobulin clones were reconstructed as antibodies, which were then used in immunoprecipitation and antigen array experiments for hypothesis-free global antigen profiling of auto- and exogenous antigens.</p><p><strong>Results: </strong>From the analysis of 13 CRSwNP patients, 31 antibodies were reconstructed from dominant B-cell clones identified in nine patients. Seven novel protein autoantigens were identified, five of which were nucleic acid-binding proteins, and all were associated with autoimmune diseases. Additionally, nine microbial antigens, including various viruses, bacteria, and fungi, were discovered. Notably, two antibodies demonstrated dual reactivity, simultaneously recognizing both microbial and human proteins. For example, one antibody targeted CMV, Clostridium tetani, and human plectin (PLEC), while another recognized Aspergillus niger and human dihydrolipoamide S-acetyltransferase (DLAT), through molecular mimicry of shared amino acid homologies.</p><p><strong>Conclusion: </strong>Our data indicate the possibility that the pathobiology of CRSwNP involves autoreactive humoral immunity, with a subset of cases potentially exhibiting molecular mimicry-driven autoimmune features triggered by microbial infections. Nevertheless, this hypothesis requires further investigation.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472273","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":"Exploring the Temporal Interplay of Allergic Sensitization and Asthma via Graph and Manifold Analysis.","authors":"Alex Cucco, Angela Simpson, Clare Murray, Adnan Custovic, Sara Fontanella","doi":"10.1016/j.jaci.2025.02.012","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.012","url":null,"abstract":"<p><strong>Background: </strong>The association between allergic sensitization and asthma is well-documented, but its precise role in asthma remains uncertain. Component-resolved diagnostics allows detailed assessment of IgE-sensitization to multiple allergenic molecules (c-sIgE). We applied advanced network embedding techniques to investigate the dynamics of temporal development of multiple c-sIgE and identify networks associated with asthma.</p><p><strong>Methods: </strong>In a population-based birth cohort, we measured c-sIgE to 112 proteins using multiplex array at 6 time-points from infancy to adolescence. We built weighted co-occurrence networks between c-sIgEs to investigate connectivity structures at different ages. To identify critical periods where networks are similar/divergent, we applied Graph embedding and dimensionality reduction techniques. We then compared network development structure between subjects with and without asthma at different ages, and analyzed topological features to compare network structures.</p><p><strong>Results: </strong>c-sIgEs sensitization networks across ages revealed significant changes and a continuous evolution rather than abrupt shifts, with networks at ages 5 and 8 being very similar. Individuals with asthma consistently exhibited more complex and interconnected networks of c-sIgEs, which became more pronounced with age. Graph embedding showed that while profiles of those with and without asthma were distinct and the separation persisted across ages. A specific set of c-sIgEs and their interactions was responsible for this distinction. Topological features of networks which distinguished between sensitized individuals with and without asthma were age dependent.</p><p><strong>Conclusions: </strong>The differences in c-sIgE networks between subjects with and without asthma are consistently observed throughout childhood. Age needs to be considered when developing interpretation algorithms for asthma diagnosis/prediction.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472191","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":"Targeting OX40-OX40L pathway: A new era in atopic dermatitis management by T cell rebalancing.","authors":"Saeko Nakajima, Satoru Yonekura, Kenji Kabashima","doi":"10.1016/j.jaci.2025.02.007","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.007","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468212","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":"Critical evaluation of feature importance assessment in proteomic analysis using skin microdialysis.","authors":"Yoshiyasu Takefuji","doi":"10.1016/j.jaci.2024.12.1096","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.12.1096","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449208","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":"From rare to more common: The emerging role of omics in improving understanding and treatment of severe inflammatory and hyperinflammatory conditions.","authors":"Salla Keskitalo, Mikko Seppänen, Antonio Del Sol, Markku Varjosalo","doi":"10.1016/j.jaci.2025.02.011","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.011","url":null,"abstract":"<p><p>Inflammation is a pathogenic driver of many diseases, including atherosclerosis and rheumatoid arthritis. 'Hyperinflammation' can be seen as any inflammatory response that is deleterious to the host, regardless of cause. In medicine, hyperinflammation is defined as severe, deleterious, fluctuating, systemic or local inflammation with presence of a cytokine storm. It has been associated with rare auto-inflammatory disorders. However, advances in omics technologies, including genomics, proteomics, and metabolomics, have revealed it to be more common, occurring in sepsis and severe COVID-19. Focusing on proteomics, this review highlights the key role of omics in this shift. Through an exploration of research, we present how omics technologies have contributed to improved diagnostics, prognostics, and targeted therapeutics in the field of hyperinflammation. We also discuss the integration of advanced technologies, multiomics approaches and artificial intelligence (AI), in analyzing complex datasets to develop targeted therapies, and their potential for revolutionizing clinical aspects of hyperinflammation. We emphasize personalized medicine approaches for effective treatments and outline challenges, including the need for standardized methodologies, robust bioinformatics tools, and ethical considerations regarding data privacy. This review aims to provide comprehensive understanding of the molecular mechanisms underpinning hyperinflammation and underscores the potential of omics technologies in enabling successful clinical management.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468183","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":"Plasmacytoid dendritic cells alleviate allergic asthma via airway epithelial cells-dependent thymosin β4 expression.","authors":"Yue Li, Zhengrong Chen, Miaomiao Han, Zhen Duan, Ruizhe Li, Xinyi Cui, Haiyan Ge, Yilai Shu, Huabin Li, Rui He","doi":"10.1016/j.jaci.2025.01.047","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.047","url":null,"abstract":"<p><strong>Background: </strong>Plasmacytoid dendritic cells (pDCs) are previously reported to induce immune tolerance to allergen by inhibiting allergic Th2 cell priming. However, there is limited knowledge on pDC function during Th2 effector phase of allergic asthma.</p><p><strong>Objective: </strong>We aimed to investigate the role of pDCs in ongoing allergic asthma following airway sensitization and challenge with house mite dust (HDM).</p><p><strong>Methods: </strong>BDCA2-DTR mice were used for pDC depletion. RNA-sequencing (RNA-seq) of sorted mouse lung pDCs, in vitro cell experiments, and in vivo CCR2 blockade or Tβ4 supplementation were performed to elucidate the underlying mechanism.</p><p><strong>Results: </strong>pDC depletion during HDM challenge enhanced CCR2-dependent inflammatory monocyte-derived cells (inf-MCs) accumulation, leading to exacerbated Th2-mediated allergic asthma phenotypes. RNA-seq analysis revealed an anti-inflammatory peptide thymosin β4 (Tβ4) among the most up-regulated genes in asthmatic lung pDCs. Airway epithelial cells-derived IL-33 was required for up-regulating Tβ4 expression in pDCs, which represented the main source of Tβ4 in asthmatic lungs. Importantly, Tβ4 supplementation reversed the exacerbation of asthmatic phenotypes in BDCA2-DTR mice. Alveolar macrophages were identified as the major source of CCL2 and the target of Tβ4 in asthmatic lungs. Mechanistically, Tβ4 inhibited IL-4/IL-13-induced phosphorylation of JAK1 and STAT6 and downstream EGR2 expression in macrophages, thereby reducing CCL2 expression and subsequent inf-MC recruitment. Unexpectedly, decreased serum Tβ4 levels were detected in mice and humans with ongoing allergic asthma. This could be due to increased uptake of Tβ4 by alveolar macrophage, which was required for its inhibitory effect on CCL2 expression.</p><p><strong>Conclusions: </strong>Lung pDCs exert anti-inflammatory effects in allergic asthma via expressing Tβ4, which could have therapeutic potential.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468189","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":"Psoriasis Harbors Multiple Pathogenic Type 17 T-cell Subsets: Selective Modulation by Risankizumab.","authors":"Jaehwan Kim, Jongmi Lee, Jongeun Lee, Katherine Kim, Xuan Li, Wei Zhou, Junyue Cao, James G Krueger","doi":"10.1016/j.jaci.2025.02.008","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.008","url":null,"abstract":"<p><strong>Background: </strong>Recent single-cell studies indicated that IL-17-producing T-cells (T17) have diverse subsets expressing IL-17A, IL-17F, or a combination of them in human psoriasis skin. However, it is unknown how T17 subsets are differently regulated by IL-23 versus IL-17A blockades.</p><p><strong>Objective: </strong>We sought to investigate how systemic monoclonal antibody injections blocking IL-23 versus IL-17A differently modify immune cell transcriptomes in human psoriasis skin.</p><p><strong>Methods: </strong>We analyzed a total of 93 human skin single-cell libraries, including 42 psoriasis pretreatment lesional skin, 25 psoriasis pretreatment non-lesional skin, 12 psoriasis posttreatment after IL-23 inhibition, 4 psoriasis posttreatment after IL-17A inhibition, and 10 control skin samples.</p><p><strong>Results: </strong>Of the six T17 cell subsets identified, an IL17A+ IFNG+ subset and an IL17F+ IL10- subset expressed the IL-23 receptor along with other inflammatory cytokines, and IL-23 inhibition downregulated these potentially pathogenic T17 subsets. In contrast, T17 cells expressing both IL-17A and IL-17F did not express the IL-23 receptor, and the percentage of this potentially non-pathogenic T17 subset increased after IL-23 inhibition. In addition, the expression of the IL-17 negative regulation genes, such as TNFAIP3, increased in myeloid cells more after IL-23 inhibition than after IL-17A inhibition.</p><p><strong>Conclusions: </strong>This study suggests multiple immune mechanisms of how IL-23 inhibition can modify the complex inflammatory environment present in psoriatic skin, highlighting the roles of specific T17 subsets in psoriasis development and background skin protection.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468207","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":"IL-36-driven pustulosis: Transcriptomic signatures match between generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis (AGEP).","authors":"Theresa Benezeder, Natalie Bordag, Johannes Woltsche, Katharina Falkensteiner, Thomas Graier, Eva Schadelbauer, Lorenzo Cerroni, Damian Meyersburg, Valeria Mateeva, Adam Reich, Marta Kołt-Kamińska, Gudrun Ratzinger, Julia-Tatjana Maul, Barbara Meier-Schiesser, Alexander A Navarini, Romana Ceovic, Knut Prillinger, Maruska Marovt, Lev Pavlovksy, Andrea Szegedi, Maria Sanzharovskaja, Herwig Zach, Peter Wolf","doi":"10.1016/j.jaci.2025.01.046","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.046","url":null,"abstract":"<p><strong>Background: </strong>Due to similarities, the distinction between generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis (AGEP) has been a matter of debate for long time.</p><p><strong>Objective: </strong>Our aim was to define the molecular features of GPP and AGEP.</p><p><strong>Methods: </strong>We analyzed skin biopsy samples and clinical data from 125 patients with AGEP, GPP, palmoplantar pustulosis (PPP), plaque psoriasis (PSO), and non-pustular cutaneous adverse drug reactions (ADRs), as well as from healthy skin controls using RNA sequencing and blinded histopathological analyses.</p><p><strong>Results: </strong>The transcriptome and histopathologic features of AGEP and GPP samples exhibited significant overlap (177 differentially expressed genes (DEGs) in GPP and AGEP compared to healthy skin, only 2 DEGs comparing AGEP and GPP), yet displayed marked differences from those of PPP, PSO, and ADR samples, with a notable number of DEGs (131 DEGs comparing AGEP and PSO, 75 DEGs comparing AGEP and PPP and 52 DEGs comparing AGEP and ADR) and pathways. A transcriptome profile subgroup evaluation of more than 13,000 analyzed genes did not reveal any differentially expressed genes in drug-induced GPP and AGEP. Moreover, the immune response pattern and immune cell composition did not differ between drug-induced GPP and AGEP, whereas non-drug-induced GPP had higher expression of Th17-related genes and a higher neutrophil count than AGEP.</p><p><strong>Conclusion: </strong>We propose that AGEP is a drug-induced variant of GPP and therefore part of IL-36-related pustulosis. A key signature overarching this spectrum was identified, thereby opening the therapeutic approach of IL-36 inhibition to all subtypes of the disease.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468185","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":"Stephan Traidl, Moritz Maximilian Hollstein, Andreas Leha, Timo Buhl","doi":"10.1016/j.jaci.2025.01.026","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.026","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449211","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}