Clinical Reviews in Allergy & Immunology最新文献

{"title":"Heterogeneity in Atopic Dermatitis: Ethnic, Anatomical Site, and Age-related Variations.","authors":"Yixuan Liu, Yizhen Li, Liangliang Sun, Hao Wu, Huibin Yin, Haihong Qin, Chaoying Gu, Christopher Chang, Wei Li","doi":"10.1007/s12016-026-09141-x","DOIUrl":"10.1007/s12016-026-09141-x","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a chronic, systematic inflammatory dermatosis with a high prevalence worldwide, characterized by multiple heterogeneities. Recent studies have highlighted variations in the incidence and manifestation of AD among different ethnic populations due to genetic and immunological differences. The severity of AD also varies by anatomical sites, influenced by factors such as regional skin microenvironment, microbiome-immune interaction, and environmental exposure. Notably, head and neck dermatitis (HND) is a refractory phenotype of AD, which responds less well to conventional and novel systemic treatment. Furthermore, distinct susceptibility factors exist across age groups, including food allergies in infants and young children, psychological stress in adults, and aging-related AD in the elderly. The heterogeneity of AD requires further exploration of the pathogenesis in different states, which also poses a significant challenge for therapy. This review synthesizes current evidence on AD heterogeneity, elucidating variations across ethnicities, anatomical sites, and age groups to guide the development of precision treatment.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":"8"},"PeriodicalIF":11.5,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218973","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":"The Geoepidemiology of Autoimmune Hepatitis.","authors":"Yang Li, Xiangzhen Meng, Patrick S C Leung, M Eric Gershwin, Diego Vergani, Junmin Song","doi":"10.1007/s12016-026-09138-6","DOIUrl":"10.1007/s12016-026-09138-6","url":null,"abstract":"<p><p>Autoimmune hepatitis (AIH) is typically a chronic, inflammatory, and progressive liver disease of autoimmune origin. Currently, two recognized types are identified in clinical practice: type 1 and type 2. The disease can occur in all geographic regions and racial/ethnic groups worldwide, but shows marked variations. This pattern reflects a complex interplay between genetic factors and environmental triggers. In this review, we aim to examine the geoepidemiological features of AIH and explore how these features relate to its etiopathogenesis, providing an integrated analysis of this complex condition. Our work may shed light on the initiation and progression of AIH, as well as its treatment and prevention.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":"7"},"PeriodicalIF":11.5,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156348","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":"The Role of Aryl Hydrocarbon Receptor in Airway Remodeling: Mechanistic Insights Across Cellular Functions.","authors":"Mohammad Irshad Reza, Ashish Kumar, Rodney D Britt, Venkatachalem Sathish","doi":"10.1007/s12016-026-09135-9","DOIUrl":"10.1007/s12016-026-09135-9","url":null,"abstract":"<p><p>Airway remodeling, a hallmark of asthma, involves structural and functional changes in the airways including extracellular matrix (ECM) deposition, airway smooth muscle (ASM) cell hypertrophy and hyperplasia, epithelial and fibroblasts remodeling, and mitochondrial dysfunction driven by chronic inflammation. The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor commonly known for mediating xenobiotic responses, has recently emerged as a key regulator of cellular processes implicated in airway remodeling. This review explores the multifaceted role of AhR in modulating proliferation, migration, ECM remodeling, contraction, and mitochondrial homeostasis across various airway structural cell types. Based on recent studies, we highlight how AhR exerts anti-proliferative effects in ASM, epithelial, and fibroblasts, modulates calcium signaling to influence contraction, and regulates ECM turnover via transforming growth factor-β and matrix metallopeptidase pathways. Additionally, the dual, ligand- and context-dependent nature of AhR activation is emphasized, with both protective and detrimental outcomes observed depending on the specific agonist and disease conditions. Collectively, this review underscores the therapeutic potential of targeting AhR in airway remodeling.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":"6"},"PeriodicalIF":11.5,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13032855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141315","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":"Neuro-immune Crosstalk in Atopic Dermatitis: A Multiaxial Regulatory Network and Novel Therapeutic Perspectives.","authors":"Wanyao Liu, Hanyi Zhang, Xiang Chen, Yi Xiao, Juan Su","doi":"10.1007/s12016-025-09127-1","DOIUrl":"10.1007/s12016-025-09127-1","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a chronic inflammatory disorder driven by complex neuro‑immune interactions beyond classical immune dysregulation. Previous reviews have largely focused on local peripheral neuro‑immune circuits mediating itch and inflammation, but they have not provided an integrative framework connecting peripheral, systemic, and psychological axes. Here, we propose a “multi‑axial neuro‑immune regulatory network” unifying cutaneous, central, and gut–brain–skin pathways to explain the systemic and psychosomatic nature of AD. We highlight neuroplastic remodeling, psycho-neuro-immunologic mechanisms, and therapeutic innovations that target these intertwined axes. This conceptual framework extends beyond prior literature by positioning AD as a dynamic neuro‑immune disorder rather than a purely epithelial or allergic disease.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":"5"},"PeriodicalIF":11.5,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112495","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":"Novel Therapeutic Strategies for Atopic Dermatitis: Biomarker Modulation and Clinical Implications. A Systematic Review.","authors":"Noelia Moreiras-Arias, Juan José Nieto-Fontarigo, Francisco Javier Salgado, Daniel González-Vilas, Carmen Paredes-Suárez, Enma Combo-García, Carmen Rodríguez-Otero, Ángeles Flórez","doi":"10.1007/s12016-025-09129-z","DOIUrl":"10.1007/s12016-025-09129-z","url":null,"abstract":"<p><p>Advances in the understanding of atopic dermatitis (AD) pathogenesis have driven the development of innovative systemic therapies targeting key immunologic pathways. This systematic review summarizes current evidence on the impact of biologic agents, Janus kinase (JAK) inhibitors, and other emerging treatments on AD-related biomarkers and their correlation with clinical outcomes. A comprehensive literature search was conducted across PubMed, Embase, Scopus, and Web of Science for studies published between 2014 and 2024. Eighty studies met the inclusion criteria. Dupilumab was the most extensively investigated therapy, followed by tralokinumab, JAK inhibitors, and novel agents such as amlitelimab, stapokibart, and tezepelumab. Across drug classes, consistent reductions in CCL17/TARC, LDH, and total IgE levels were observed, generally paralleling clinical improvement in EASI and SCORAD scores. Transcriptomic and proteomic analyses revealed normalization of Th2/Th22 inflammatory signatures and restoration of barrier-related gene expression, while microbiome studies showed a reduction in Staphylococcus aureus colonization. Despite these advances, the heterogeneity of study designs and analytical techniques limits the comparability of results. CCL17 and LDH currently represent the most reliable biomarkers associated with disease severity and treatment response, although their limited specificity restricts clinical applicability. Future research should aim to validate integrated biomarker panels combining immunologic, transcriptomic, and microbiomic data to enable precision medicine approaches in atopic dermatitis management.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":"4"},"PeriodicalIF":11.3,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12855363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146084492","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":"Atopic Comorbidities and Topical Steroids in Early Childhood Atopic Dermatitis: Are We Missing a Piece of the Puzzle?","authors":"Courtney A Chau, Sonya L Cyr, Ruchi Gupta, Peter Lio","doi":"10.1007/s12016-025-09131-5","DOIUrl":"10.1007/s12016-025-09131-5","url":null,"abstract":"<p><p>Topical corticosteroids (TCS) remain the first-line treatment for (AD). This narrative review examines clinical data on the immunomodulatory effects of TCS and recent treatments for atopic dermatitis (AD) in early childhood in the context of atopic comorbidities. While TCS are effective in reducing several markers of inflammation in infants with AD, certain type 2 cytokines, such as interleukin (IL)−4, IL-5, and IL-13, remain uncontrolled in the infant stratum corneum, a major source of dysregulated systemic cytokines. A pathomechanism known as remote priming has been identified, wherein allergen-induced antigen-specific immune responses in disrupted skin facilitate allergen-sensitizing immune responses in distant mucosal barrier sites, such as the gut or lung. In the gut, remote priming occurs through the activation of epidermal type 2 innate lymphoid cells (ILC2), which prime gut mast cells and promote food allergies. ILC2s produce IL-5 and IL-13, which remain present in the epidermis with TCS. Consequently, ILC2 cells in the skin of children with AD may remain able to contribute to remote gut priming. Type 2 cytokines also promote immunoglobulin E (IgE) production—a marker of atopic development in children. Over 16 weeks, children aged 6 months to 5 years treated with dupilumab and TCS show a 70% reduction in IgE levels, whereas those treated with TCS alone exhibit a 30% increase in IgE levels. These observations highlight the need for a more comprehensive approach to managing infant AD. Therapies that target inflammation originating from both innate and adaptive effector cells involved in type 2 inflammation may not only alleviate the burden of AD but also disrupt the progression of the atopic march.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":"3"},"PeriodicalIF":11.5,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12847183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050658","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":"Model-Based Meta-Analysis of IL-17 A Inhibitors for Moderate-to-Severe Plaque Psoriasis: Establishing Exposure-Response Relationships to Inform Targeted Drug Development.","authors":"Yixiao Liu, Xiaoya Chen, Ling Xu, Qingshan Zheng, Lujin Li","doi":"10.1007/s12016-025-09123-5","DOIUrl":"10.1007/s12016-025-09123-5","url":null,"abstract":"<p><p>This study aimed to establish an exposure-response model for IL-17 A inhibitors to predict the clinical efficacy of novel agents based on in vitro potency and pharmacokinetic parameters, guiding the development of new IL-17 A-targeting therapies. A systematic literature search was conducted in PubMed, Cochrane Library, and Embase to identify randomized controlled trials of three FDA-approved IL-17 A inhibitors: secukinumab, ixekizumab, and bimekizumab. Primary endpoints included PASI 75 and PASI 90. Pharmacokinetic parameters were extracted from FDA and EMA review documents, while the half-maximal inhibitory concentration (IC₅₀) values came from published studies. An exposure-response model was developed to characterize treatment effects in moderate-to-severe plaque psoriasis and externally validated using clinical data of xeligekimab. A total of 30 clinical trials involving 12,491 subjects were included. The model accurately described the time-effect characteristics of the PASI 75/90 response rates of the three IL-17 A inhibitors. Average drug concentration (C_av) was the most relevant exposure metric. The IC₅₀ value significantly influenced exposure-response outcomes, and lower IC₅₀ values required lower C_av for comparable efficacy. External validation showed high predictive accuracy for xeligekimab. A reference table was also constructed to estimate required doses based on IC₅₀ and desired therapeutic targets, facilitating rational dose selection. Based on existing pharmacokinetic and clinical efficacy data of IL-17 A inhibitors, this study successfully developed a streamlined and accurate exposure-response model, offers a practical tool for efficacy prediction and dose optimization in the development of novel agents targeting IL-17 A.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":"2"},"PeriodicalIF":11.5,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145987971","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":"Baseline Blood Eosinophil Count for Identifying Superior Responders to Biologics in Chronic Rhinosinusitis with Nasal Polyps: A Systematic Review and Meta-Analysis.","authors":"Yang Zheng, Wei Liu, Yujuan Yang, Haoran Lu, Huikang Wang, Zhen Liu, Congxian Lu, Jianbo Fu, Yingxue Li, Xicheng Song, Yu Zhang","doi":"10.1007/s12016-025-09130-6","DOIUrl":"10.1007/s12016-025-09130-6","url":null,"abstract":"<p><p>Current guidelines recommend the presence of type 2 inflammation as one of the indications for biologic therapy in chronic rhinosinusitis with nasal polyps (CRSwNP). Although blood eosinophil (Eos) levels are commonly used as a biomarker for type 2 inflammation, their value in predicting differential responses to biologic treatment has not been verified by high-quality evidence. We searched the PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (Central) databases, and hand-searched Clinicaltrials.gov for all RCTs that used biologic therapies for CRSwNP. Primary outcomes included the nasal polyp score (NPS), nasal congestion score (NCS), a 22-item sino-nasal outcome test (SNOT-22) score, and loss of smell (Los) score. This study is registered with PROSPERO (CRD420251063136). This meta-analysis included 9 studies comprising 10 RCTs (n = 2,551), all of which were judged to be at a high risk of selection bias. The results showed that when compared with placebo treatment, biologic therapy significantly improved all outcome measures, including the NPS, NCS, SNOT-22 score, and LoS score, —regardless of baseline Eos levels. However, inter-subgroup comparisons clearly showed that both the Eos ≥ 150 cells/µL and Eos ≥ 300 cells/µL groups had significantly greater improvements in their NPS and NCS when compared with the Eos < 150 cells/µL group (p < 0.05). In contrast, improvements in the SNOT-22 scores and LoS scores were comparable across all subgroups, with no statistically significant differences observed. An exploratory analysis suggested that at the Eos ≥ 300 cells/µL threshold, anti-IL-4Rα monoclonal antibodies may be superior to anti-IL-5 monoclonal antibodies for improving the NPS and NCS (p < 0.05). Although biologics demonstrate efficacy in the overall CRSwNP population, a baseline blood eosinophil count ≥ 150 cells/µL pinpoints the patient subgroup with a superior response.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":"1"},"PeriodicalIF":11.5,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896458","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":"Comparative Efficacy of Combined and Standalone Oral Immunotherapies for Peanut Allergy: a Bayesian Network Meta-Analysis of RCTs.","authors":"Xinyu Tian, Shuang Liu, Lisha Li, Kai Guan","doi":"10.1007/s12016-025-09118-2","DOIUrl":"10.1007/s12016-025-09118-2","url":null,"abstract":"<p><strong>Background: </strong>Peanut allergy is a chronic IgE-mediated disease with potentially life-threatening consequences. While several immunotherapeutic strategies have emerged, including oral immunotherapy (OIT), omalizumab (OMA)-based therapies, and probiotic and peanut oral immunotherapy (PPOIT), the comparative effectiveness of these interventions remains unclear. This study aimed to evaluate the relative efficacy and safety of combined and standalone oral immunotherapies for peanut allergy using a Bayesian network meta-analysis (NMA).</p><p><strong>Methods: </strong>A systematic literature search was conducted in PubMed, EMBASE, and Web of Science up to March 2025. We included randomized controlled trials (RCTs) involving patients with IgE-mediated peanut allergy who received OIT + OMA, OMA monotherapy, OIT alone, or PPOIT. Outcomes included low-dose and high-dose desensitization, sustained unresponsiveness (SU), and safety outcomes (adverse events, AEs). The risk of bias was assessed using RoB 2. Analyses were performed using R software (version 4.4.3) with Bayesian NMA methods.</p><p><strong>Results: </strong>Nineteen RCTs involving 2040 participants were included. Based on Probability Scores (P-scores), OIT + OMA demonstrated the highest efficacy for both low- (P-score: 97.20%) and high-dose desensitization (96.69%), followed by PPOIT (70.15% and 51.16%), OIT third (64.40% and 52.72%), and OMA fourth (75.29% and 71.21%). PPOIT and OIT showed moderate efficacy for SU. OIT was associated with a higher frequency of AEs compared with placebo.</p><p><strong>Conclusions: </strong>Combination and modified immunotherapies may offer improved efficacy and safety profiles, though results should be interpreted in the context of limited data and study heterogeneity.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"113"},"PeriodicalIF":11.3,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12748126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145854833","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":"Immunopathogenesis and Therapeutics of Systemic Lupus Erythematosus: an Integrative Review.","authors":"Qian Lyu, Huan Zou, Shen Hu","doi":"10.1007/s12016-025-09119-1","DOIUrl":"10.1007/s12016-025-09119-1","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a chronic, heterogeneous autoimmune disease with a strong female predisposition, characterized by multi-organ inflammation and damage. Its pathogenesis arises from a complex interplay of genetic susceptibility, epigenetic alterations, hormonal influences, and environmental triggers. This confluence drives a sustained loss of self-tolerance and profound immune dysregulation. Innate immune dysfunction, featuring unchecked type I interferon (IFN) production and defective clearance of cellular debris, exposes autoantigens. Concurrent adaptive immune defects include a breakdown of B and T cell tolerance, leading to pathogenic autoantibody production, dysregulated cytokine networks, and aberrant lymphocyte interactions. These processes culminate in tissue injury via immune complex deposition and direct cellular effects. This review synthesizes current understanding of these multifaceted immunological mechanisms in SLE, underscoring how their delineation has informed the development of targeted biologic therapies and highlighting the ongoing need for translational research to improve patient outcomes. Furthermore, emerging insights into the heterogeneity of immune pathways among patients emphasize the potential for personalized treatment approaches tailored to specific molecular profiles.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"112"},"PeriodicalIF":11.5,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848640","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}