Clinical Reviews in Allergy & Immunology最新文献

{"title":"Allergic Rhinitis is Associated with Increased Suicidality: A Systematic Review and Meta-Analysis.","authors":"Simon Høj, Frederik Kronvold Nielsen, Bo Chawes, Vibeke Backer, Allan Linneberg, Simon Francis Thomsen, Torben Sigsgaard, Howraman Meteran","doi":"10.1007/s12016-025-09061-2","DOIUrl":"https://doi.org/10.1007/s12016-025-09061-2","url":null,"abstract":"<p><p>Allergic rhinitis (AR) is a common inflammatory condition affecting millions globally. Emerging evidence suggests a potential link between AR and suicidality; however, this association remains underexplored compared to other atopic diseases. This systematic review and meta-analysis aimed to investigate the association between AR and the risks of suicidal ideation, attempts, and death. Following PRISMA guidelines, we conducted a systematic search across PubMed, Embase, PsycINFO, Cochrane databases, Web of Science, Scopus, CINAHL, and Google Scholar. A total of 590 studies were screened, with 9 eligible cross-sectional studies involving 1,604,962 participants included. Data on suicidal ideation, suicide attempts, and death were synthesized using random-effects meta-analyses. Odds ratios (ORs) were calculated with 95% confidence intervals (CIs). The risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist, and evidence was graded using the GRADE framework. AR was not significantly associated with suicidal ideation (OR: 1.12, 95% CI: 0.97-1.30; 1,101,819 participants from 7 studies). However, AR patients demonstrated an elevated risk of suicide attempts (OR: 1.25, 95% CI: 1.00-1.57; 1,554,297 participants from 5 studies) and suicide death (OR: 1.65, 95% CI: 1.46-1.86; 478,244 participants from 2 studies). This meta-analysis highlights an association between allergic rhinitis and increased risk of suicide attempts and death. However, due to the cross-sectional nature of included studies, causality cannot be inferred.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"52"},"PeriodicalIF":8.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Bias in Systemic Sclerosis: from Clinical to Immunological Differences.","authors":"Lazaros I Sakkas, Dimitrios P Bogdanos, Ian C Chikanza","doi":"10.1007/s12016-025-09062-1","DOIUrl":"10.1007/s12016-025-09062-1","url":null,"abstract":"<p><p>Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by microvasculopathy, extensive fibrosis, and autoantibodies. The disease affects mostly the female sex. In this review, we highlight sex bias in clinical manifestations in SSc, and the pathophysiological changes underlying this bias. Male sex is associated with the diffuse cutaneous form of the disease, digital ulcers, interstitial lung disease, and worse prognosis. These clinical differences can be attributed to sex hormones and sex chromosomes, as females differ from males in sex hormones (estrogens in females, androgens in males) and sex chromosomes (XX in females, XY in males). Estrogens in females generally have immunostimulatory and profibrotic effects, and androgens have immunosuppressive effects. The X-chromosome contains many immunity-related genes, but the double dose of X-linked genes in females is avoided by random inactivation of one X-chromosome (XCI). However, many X-linked immunity-related genes, including toll-like receptor (TLR)7, TLR8 and Bruton's tyrosine kinase (BTK), escape XCI resulting in a biallelic expression with pathophysiological implications. Also, autosomal genes are differentially expressed between sexes. Therefore, sex should be included in future studies on SSc to aid in forming predictive algorithms and helping therapeutic decisions in this difficult-to-treat disease.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"51"},"PeriodicalIF":8.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage-Centric Immunometabolic Crosstalk in Alopecia Areata Pathogenesis: Mechanisms and Therapeutic Implications.","authors":"Xu Liu, Xiuzu Song","doi":"10.1007/s12016-025-09060-3","DOIUrl":"https://doi.org/10.1007/s12016-025-09060-3","url":null,"abstract":"<p><p>Although alopecia areata (AA) is recognized as a hair loss disorder stemming from the dysregulation of cutaneous immune homeostasis, its precise pathogenesis still remains elusive. The collapse of hair follicle (HF) immune privilege (IP), leading to immune cell-mediated attack on the hair follicle, is currently the widely accepted fundamental mechanism of AA. Among the immune cells studied in this context, CD8⁺ T cells and regulatory T (Treg) cells are relatively well-researched, but the direct involvement of macrophages in the disease process has been less frequently demonstrated. In this review, we summarize various previous studies on macrophages and hypothesize the immune mechanisms by which macrophages contribute to the pathogenesis of AA. This exploration provides new insights for future research and potential clinical treatments.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"50"},"PeriodicalIF":8.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atopic Dermatitis: The Relationship Between Immune Mediators and Skin Lipid Barrier.","authors":"Huayan You, Yunsheng Liang","doi":"10.1007/s12016-025-09057-y","DOIUrl":"https://doi.org/10.1007/s12016-025-09057-y","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a chronic inflammatory skin disease that is prevalent worldwide with complex etiology. Skin barrier defects and abnormal immune activation are crucial in the occurrence and development of AD. In the classic model of the skin barrier, lipids are essential for the formation and maintenance of this barrier as a \"mortar\" component. However, abnormally activated immune responses promote the lipid barrier deficiency through the secretion of various types of immune mediators directly or indirectly. In this review, we first introduce the skin lipid barrier (SLB) under both normal and abnormal conditions, highlighting the contributions of lipids derived from keratinocytes and sebaceous glands (SGs). Subsequently, the relationships between the immune mediators of Th1, Th2, Th17, Th22, and other types (adipokines, prostaglandins, leukotrienes) and SLB are elaborated in turn. Finally, the therapies for restoring SLB to treat AD are summarized, with a focus on the restoration effect of dupilumab on SLB. We hope that this review will offer a comprehensive perspective for understanding the pathogenesis of lipid metabolism disorders and SLB deficiency caused by immune mediators in AD. It also aims to provide guidance for further research on targeting inflammatory mediators to restore SLB.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"49"},"PeriodicalIF":8.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophilic Urticarial Dermatosis: A Window into Systemic Inflammation and Autoimmune Disorders.","authors":"Xiaoxuan Cai, Yihe Zheng, Changyi Yang, Jiali Xu, Hong Fang, Jianjun Qiao","doi":"10.1007/s12016-025-09056-z","DOIUrl":"https://doi.org/10.1007/s12016-025-09056-z","url":null,"abstract":"<p><p>Neutrophilic urticarial dermatosis (NUD) is a distinctive dermatological manifestation that is commonly associated with systemic autoinflammatory and autoimmune diseases. This review comprehensively explores NUD in the context of five major conditions: Schnitzler syndrome, Still's disease, cryopyrin-associated periodic syndrome, systemic lupus erythematosus, and VEXAS syndrome. For each condition, a detailed discussion of the underlying mechanisms, clinical presentations, diagnostic criteria, and treatment strategies is provided. In addition, cases exhibiting features similar to NUD are emphasized, with a comprehensive examination of the pathological characteristics, particularly focusing on neutrophilic epitheliotropism. This review underscores the significance of identifying NUD as a potential indicator of systemic autoimmune disorders and discusses the role of skin biopsy and laboratory tests in diagnosing the underlying etiology. Finally, a diagnostic framework for NUD is proposed, highlighting the importance of a multidisciplinary assessment to ascertain the underlying systemic condition responsible for the dermatological manifestations. The objective of this review is to enhance the comprehension of NUD, thereby facilitating early diagnosis and the implementation of targeted strategies for affected patients.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"48"},"PeriodicalIF":8.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Diagnosis to IgE-mediated Wheat Allergy and Wheat-Dependent Exercise-Induced Anaphylaxis.","authors":"Witchaya Srisuwatchari, Kantima Kanchanapoomi, Punchama Pacharn","doi":"10.1007/s12016-025-09059-w","DOIUrl":"https://doi.org/10.1007/s12016-025-09059-w","url":null,"abstract":"<p><p>IgE-mediated wheat allergy is an emerging problem worldwide, particularly prevalent in Northern Europe and parts of Asia. Another unique manifestation of wheat allergy, wheat-dependent exercise-induced anaphylaxis (WDEIA), and hydrolyzed wheat protein-induced urticaria/anaphylaxis/WDEIA, has increasingly been reported in recent decades. Major wheat protein allergens are classified into two main categories: water/salt-soluble proteins (e.g., alpha-amylase inhibitors, lipid transfer proteins (LTP), and avenin-like proteins) and alcohol/diluted acid-soluble proteins (e.g., gliadins and glutenins). The most allergenic wheat proteins responsible for IgE-mediated wheat allergy are gliadins, particularly omega (ω)-5-gliadin, and glutenins. In cases of WDEIA, ω-5-gliadin and LTP have been identified as the major allergens involved. Diagnostic challenges for IgE-mediated wheat allergy and WDEIA exist due to the variable sensitivity and specificity of currently available tests, including skin prick tests (SPT) and serum-specific IgE (sIgE), which may lead to misdiagnosis. These variations in diagnostic value may be attributed to factors such as clinical presentation, the specific allergens involved, the type of SPT extracts used, and the component tested. Additionally, in countries where grass pollen is a primary sensitizer, in vivo or in vitro cross-reactivity between timothy grass and wheat is common. However, this cross-reactivity is usually asymptomatic and lacks clinical significance. Diagnostic methods have been developed to minimize the risks associated with oral food challenge tests (OFC). Novel approaches, including component-resolved diagnostics (CRD), basophil activation tests (BAT), and epitope-specific antibody assays, provide more precise diagnostic options for IgE-mediated wheat allergy, WDEIA, and its subtypes by targeting specific allergens and components. However, further large-scale studies and validations are required to standardize these diagnostic protocols.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"47"},"PeriodicalIF":8.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms and Therapeutic Implications of EZH2 in Nasal Diseases.","authors":"Jiani Li, Meng Wang, Jing Yang, Zhiwei Cao, Zhaowei Gu, Yunxiu Wang","doi":"10.1007/s12016-025-09058-x","DOIUrl":"https://doi.org/10.1007/s12016-025-09058-x","url":null,"abstract":"<p><p>Enhancer of zeste homolog 2 (EZH2), a protein encoded by the EZH2 gene, is a crucial subunit in polycomb repressive complex 2. EZH2 controls the transcription of genes critical for cell proliferation, differentiation, amplification, and function through both methylated and unmethylated functions. EZH2 is considered to be a transcriptional suppressor protein when it controls histone methylation. Its dysregulation is related to a variety of cancers, with significant evidence showing its role in prostate cancer and breast cancer. EZH2 is also thought to be involved in the differentiation and function of immune cells. Ongoing research on EZH2 has revealed the correlation between inflammatory nasal diseases, the occurrence and development of nasal sinus tumors, and EZH2. This article aimed to review the research progress on the role of EZH2 in nasal diseases and explore the possibility of future EZH2-targeted therapies for nasal diseases.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"46"},"PeriodicalIF":8.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Questionnaire for Clinical Diagnosis of House Dust Mite's Allergy Approved by Delphi Consensus.","authors":"Angelica Tiotiu, Fulvio Braido, Krysztof Kowal, Guillermo Guidos Fogelbach, Herberto Chong Neto, Juan Carlos Ivancevich, Daniela Muti, Francisco-Javier Gonzalez-Barcala, Paschalis Steiropoulos, Silviya Novakova, Denislava Nedeva, Plamena Novakova, Stefan Mihaicuta, Jonathan Bernstein, Arzu Yorgancioglu, Pierachille Santus, Andras Bikov, Giorgio Walter Canonica, Charles Pilette","doi":"10.1007/s12016-025-09055-0","DOIUrl":"https://doi.org/10.1007/s12016-025-09055-0","url":null,"abstract":"<p><p>Despite house dust mite (HDM)-allergy is the most frequent in the world, no standard questionnaire exists to help physicians in their clinical practice for screening patients with this possible diagnosis. The objective of this survey was to develop a questionnaire that could be used to identify patients with suspicion of HDM-allergy. The survey was conducted using the Delphi methodology. Nineteen international experts in allergology constituted the scientific board who established the items included in the first version of the questionnaire, defined the criteria of the selection for the next steps, and validated the final questionnaire and its interpretation. The initial version of the questionnaire included 15 items. For each item, five answers were suggested graduated by scores from \"no importance\" to \"very high importance.\" The predefined conditions for the item selection after each round were a median score ≥ 7 and > 50% of responses according \"high importance\" and \"very high importance.\" The electronic survey circulated within the Interasma Scientific Network platform. Eight questions based on the occurrence/worsening of symptoms induced by HDM-allergen exposure meet the survey criteria after the second and the third rounds and were included in the final questionnaire. Binomial answers for each question with 1 point accorded for \"Yes\" and none for \"No\" were suggested for the final version with a score ≥ 5 points associated with a high probability for HDM-allergy. By applying the Delphi process, we generated a brief questionnaire with binomial answers, easy to use in clinical practice for screening patients with HDM-allergy.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"45"},"PeriodicalIF":8.4,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting IL-13 and IL-4 in Asthma: Therapeutic Implications on Airway Remodeling in Severe Asthma.","authors":"Lina Sahnoon, Khuloud Bajbouj, Bassam Mahboub, Rifat Hamoudi, Qutayba Hamid","doi":"10.1007/s12016-025-09045-2","DOIUrl":"https://doi.org/10.1007/s12016-025-09045-2","url":null,"abstract":"<p><p>Asthma is a chronic respiratory disorder affecting individuals across all age groups. It is characterized by airway inflammation and remodeling and leads to progressive airflow restriction. While corticosteroids remain a mainstay therapy, their efficacy is limited in severe asthma due to genetic and epigenetic alterations, as well as elevated pro-inflammatory cytokines interleukin-4 (IL-4), interleukin-13 (IL-13), and interleukin-5 (IL-5), which drive structural airway changes including subepithelial fibrosis, smooth muscle hypertrophy, and goblet cell hyperplasia. This underscores the critical need for biologically targeted therapies. This review systematically examines the roles of IL-4 and IL-13, key drivers of type-2 inflammation, in airway remodeling and their potential as therapeutic targets. IL-4 orchestrates eosinophil recruitment, immunoglobulin class switching, and Th2 differentiation, whereas IL-13 directly modulates structural cells, including fibroblasts and epithelial cells, to promote mucus hypersecretion and extracellular matrix (ECM) deposition. Despite shared signaling pathways, IL-13 emerges as the dominant cytokine in remodeling processes including mucus hypersecretion, fibrosis and smooth muscle hypertrophy. While IL-4 primarily amplifies inflammatory cascades by driving IgE switching, promoting Th2 cell polarization that sustain cytokine release, and inducing chemokines to recruit eosinophils. In steroid-resistant severe asthma, biologics targeting IL-4/IL-13 show promise in reducing exacerbations and eosinophilic inflammation. However, their capacity to reverse established remodeling remains inconsistent, as clinical trials prioritize inflammatory biomarkers over long-term structural outcomes. This synthesis highlights critical gaps in understanding the durability of IL-4/IL-13 inhibition on airway structure and advocates for therapies combining biologics with remodeling-specific strategies. Through the integration of mechanistic insights and clinical evidence, this review emphasizes the need for long-term studies utilizing advanced imaging, histopathological techniques, and patient-reported outcomes to evaluate how IL-4/IL-13-targeted therapies alter airway remodeling and symptom burden, thereby informing more effective treatment approaches for severe, steroid-resistant asthma.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"44"},"PeriodicalIF":8.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhalant Mediated Allergy: Immunobiology, Clinical Manifestations and Diagnosis.","authors":"Ki Lam, Elaine Au, W K Ip, Jenna K Tam, Patrick S C Leung","doi":"10.1007/s12016-025-09053-2","DOIUrl":"https://doi.org/10.1007/s12016-025-09053-2","url":null,"abstract":"<p><p>Inhalant allergen-mediated respiratory diseases, including asthma and allergic rhinitis, have become increasing global health issues. While air pollution is believed to favor allergic sensitization and intensify clinical symptoms of allergy, allergen sensitization can vary highly with geographical location, climate, and lifestyle differences. Pollen sensitization is higher in European countries, while dust mite is more common in regions with high humidity. Domestic pet sensitization is on the rising trend in industrialized nations, but the paradoxical effect of intensive cat exposure in early childhood is also observed. Clinical management of inhalant allergic diseases has greatly benefited from the immunological and mechanistic understanding of pathophysiology. In this review, we discuss the current knowledge on inhalant mediated allergic disorders with emphasis on (1) the major immune cells and relevant chemokines and cytokines in the sensitization and effector phase with aeroallergen exposure, (2) their manifestation in asthma and allergic rhinitis, (3) characterization of inhalant allergens, (4) chemical contributions to the development of allergic diseases, and (5) clinical diagnosis of aeroallergen sensitization and management of inhalant allergy. Knowledge on the role of Th2 skewing, IgE, basophil, mast cells, and eosinophils in respiratory allergic diseases are fundamental in the diagnosis and management of these disorders. Skin test, basophil activation test, and specific IgE component-resolved diagnostics are used for diagnosis and facilitate further management. Advances in the development of biologics and allergen-specific immunotherapy will strategize the future approaches in the clinical care of respiratory allergic diseases.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"43"},"PeriodicalIF":8.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12000167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}