Clinical Reviews in Allergy & Immunology最新文献

{"title":"Immune Checkpoint Dysfunction Remodels Adaptive Immune Receptor Repertoires in CTLA-4 Insufficiency and LRBA Deficiency.","authors":"Gökhan Cildir, Selin Cildir, Rahmi Kutay Erdogan, Umran Aba, Sule Haskologlu, Selcen Bozkurt, Necmiye Ozturk, Caner Aytekin, Nicholas I Warnock, Chung Hoow Kok, Damla Pehlivan, Canberk Ipsir, Ceren Yarimkaya, Bade Sila Karatas, Nihan Doga Kozanli, Feyza Bayram Catak, Mehmet Cihangir Catak, Gülşah Merve Kılınç, Gunes Esendagli, Hamdullah Yanik, Dilek Ozcan, Mahir Serbes, Candan Islamoglu, Sara Sebnem Kilic, Yasin Karali, Salim Can, Melek Yorgun Altunbas, Esra Karabiber, Cigdem Aydogmus, Sait Karaman, Fatih Celmeli, Gul Ergen Yildiz, Emine Vezir, Gulay Irem Parlak Özel, Sevgi Keles, Ismail Reisli, Sukru Nail Guner, Mehmet Yavuz Ozbey, Alisan Yildiran, Şefika İlknur Kökçü Karadağ, Nesrin Gulez, Ferah Genel, Figen Celebi Celik, Ozgen Soyoz, Neslihan Edeer Karaca, Guzide Aksu, Tugba Arikoglu, Aylin Kont Ozhan, Semanur Kuyucu, Sevgi Bilgic-Eltan, Elif Karakoc-Aydiner, Ilhan Tezcan, Figen Dogu, Aydan Ikinciogullari, Ahmet Ozen, Safa Baris, Baran Erman","doi":"10.1007/s12016-026-09209-8","DOIUrl":"https://doi.org/10.1007/s12016-026-09209-8","url":null,"abstract":"<p><p>Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a critical negative regulator of T-cell activation, and its function is impaired either directly in CTLA-4 insufficiency or indirectly through LRBA deficiency. Although the immunological consequences of these closely related inborn errors of immunity (IEI) have been extensively characterized, their impact on adaptive immune receptor repertoires (AIRRs) remains poorly understood. Here, we performed a comprehensive analysis of αβ T-cell receptor (TCR) and B-cell receptor (BCR) repertoires in patients with CTLA-4 insufficiency and LRBA deficiency using high-resolution AIRR sequencing (AIRR-seq). Total and naïve CD4⁺ and CD8⁺ T-cell subsets were purified from patients with CTLA-4 insufficiency (n = 11), LRBA deficiency (n = 10), and healthy controls (n = 11), followed by sequencing of complete TRA and TRB V(D)J regions. Bulk sequencing of IgM and IgG heavy-chain repertoires was additionally performed in a subset of patients. Both CTLA-4 insufficiency and LRBA deficiency were associated with marked restriction of the αβ TCR repertoire, with the most pronounced abnormalities observed in the CD8⁺ compartment. Notably, repertoire restriction extended into the naïve CD8⁺ T-cell compartment in LRBA-deficient patients. In contrast, the IgM repertoire remained broadly preserved despite enrichment of the autoreactivity-associated IGHV4-34 gene segment, whereas the switched IgG repertoire was significantly restricted. Collectively, these findings demonstrate that inherited disruption of the CTLA-4/LRBA axis profoundly remodels AIRRs, preferentially affecting CD8⁺ T-cell diversity while also constraining humoral immunity, and highlight a central role for this immune checkpoint pathway in maintaining adaptive immune repertoire diversity and clonal homeostasis.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223451","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":"Type 2 Inflammation in Airway Diseases: Eosinophilic Bronchiectasis as an Emerging Phenotype.","authors":"Carlo Lombardi, Marcello Cottini, Francesco Menzella, Rory Chan, Riccardo Corbellari, Alvise Berti","doi":"10.1007/s12016-026-09207-w","DOIUrl":"https://doi.org/10.1007/s12016-026-09207-w","url":null,"abstract":"<p><p>Bronchiectasis is a chronic and highly heterogeneous airway disease traditionally regarded as a neutrophil-dominated condition driven by persistent infection and dysregulated innate immunity. Over the last decade, this traditional view has been increasingly challenged by the identification of distinct inflammatory phenotypes with important biological and therapeutic implications.Among these, eosinophilic bronchiectasis has emerged as a clinically meaningful and mechanistically distinct phenotype, characterized by type 2 (T2) immune activation, eosinophil-driven airway inflammation, and differential responsiveness to targeted therapies.In this narrative review, we provide an overview of eosinophilic bronchiectasis, emphasizing epidemiology, immunopathogenesis, and cellular and molecular mechanisms underlying airway damage and remodelling. We discuss key pathways involving eosinophils, epithelial-immune interactions, and T2 cytokine signalling, as well as established and emerging biomarkers for phenotype identification.We proposed a diagnostic framework and definitions for eosinophilic bronchiectasis, i.e. definite (airway eosinophilia with sputum or bronchoalveolar lavage eosinophils ≥ 3%), probable (persistent peripheral blood eosinophilia ≥ 300 cells/µL), and possible (a single elevated blood eosinophil count of ≥ 150-300 cells/µL or elevated FeNO > 25 ppb in the absence of asthma), to be provisionally used in the absence of shared consensus criteria.Particular attention is devoted to therapeutic implications, including biologic agents targeting the IL-5/IL-5r axes and novel disease-modifying strategies for eosinophilic disorders. Finally, we highlight unmet needs and future research directions toward precision medicine approaches aimed at improving outcomes in this increasingly recognized bronchiectasis phenotype.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223521","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":"Single-cell Transcriptomics in Autoimmune Diseases: Mechanistic Insights, Cross-disease Convergence, and Translational Challenges in Rheumatoid Arthritis, Systemic Lupus Erythematosus, Type 1 Diabetes, and Multiple Sclerosis.","authors":"Thanh-Hong Nguyen, Tuan-Dinh Nguyen, Oanh-Thi Hoang, Thuy-Thu T Can, Minh-Huyen T Nguyen, Mai-Hoang Tran, Hieu-Chi Chu, Dinh-Van Nguyen","doi":"10.1007/s12016-026-09211-0","DOIUrl":"10.1007/s12016-026-09211-0","url":null,"abstract":"<p><p>Autoimmune diseases are characterized by loss of immune tolerance and substantial heterogeneity across patients, tissues, and disease stages. Although bulk transcriptomic studies have identified important inflammatory pathways, they cannot directly resolve rare, transitional, and tissue-contextualized cell states that may be relevant to disease mechanisms and therapeutic response. Single-cell RNA sequencing (scRNA-seq) enables transcriptomic profiling at cellular resolution, while complementary multimodal, receptor-repertoire, epigenomic, and spatial approaches can link cellular states to protein phenotype, clonal architecture, regulatory programs, and tissue context. This review critically examines recent single-cell studies in rheumatoid arthritis, systemic lupus erythematosus and lupus nephritis, type 1 diabetes, and multiple sclerosis. Rather than providing a descriptive catalogue of published studies, we assess the strength of available evidence by distinguishing independently replicated findings from observations supported by limited studies, and cross-sectional associations from longitudinal, treatment-response, and functional evidence. Across the selected diseases, studies repeatedly report inflammatory programs involving interferon signaling, chemokine-mediated immune recruitment, and stromal-immune interactions; however, evidence for convergence at the cell-state and regulatory-network levels remains limited, and the extent to which shared signatures represent common pathogenic mechanisms rather than inflammatory context remains uncertain. We evaluate the translational potential of scRNA-seq for biomarker discovery, patient stratification, and treatment response prediction, while considering evidence from related tissue-based molecular stratification approaches, including the R4RA randomized trial in rheumatoid arthritis. R4RA provides prospective randomized evidence that synovial molecular features can enrich for differential therapeutic responses, but its use of bulk synovial transcriptomics and histopathology does not constitute prospective validation of single-cell-derived biomarkers. We further highlight cohort biases, reproducibility challenges, dissociation artifacts, computational ambiguity, and privacy concerns that constrain immediate clinical implementation. Together, these advances position single-cell profiling as a mechanistic discovery platform with substantial translational promise, contingent on standardization, validation across diverse cohorts, and integration with functional perturbation approaches.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179682","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":"Food-Associated Kounis Syndrome: Clinical Spectrum and Diagnostic Considerations from a Case Report and Systematic Qualitative Synthesis of Published Cases.","authors":"Sergio Sanchez-Fernandez, Gabriel Gastaminza Lasarte, Carmen D'Amelio Garófalo, Enrique Paredes-Gutierrez, Alfonso Calvo Alonso, José Bodero-Sánchez, Edurne Cerrada Uribesalgo, Lucía Parrado Gil, Irene Martín De Prado, Jimena Crespo Quirós, Laura Argiz Álvarez, Aitor Hernández Hernández, Elisa Fernández Elías, Teresa Toscano de Las Heras","doi":"10.1007/s12016-026-09210-1","DOIUrl":"10.1007/s12016-026-09210-1","url":null,"abstract":"<p><p>Kounis syndrome (KS) is a hypersensitivity-associated acute coronary syndrome. Food-associated KS remains poorly characterized, and its clinical presentation may be mimicked by non-immune food-related toxic reactions. To characterize the food exposures, clinical and cardiovascular presentations, allergological assessment, potential cofactors, KS phenotypes, management, and outcomes reported in food-associated KS. PubMed, Scopus, and Web of Science Core Collection were searched from inception to August 22, 2026. Original case reports, case series, and sufficiently informative conference reports describing objective coronary involvement temporally associated with a food or food-derived exposure were included. Patient-level data were synthesized qualitatively. KS diagnostic certainty, coronary phenotype, food causality, and presumed mechanism were assessed separately. Planned sensitivity analyses restricted the synthesis to confirmed or suspected food allergy, definite or probable KS, and cases without epinephrine administration before coronary onset or its first objective documentation. The synthesis included 50 publications or reports describing 53 unique patients. Food-related mechanisms comprised confirmed food allergy in 20 patients, clinically suspected food allergy in 26, scombroid poisoning in six, and a Coprinopsis atramentaria-alcohol interaction in one. The reported coronary spectrum ranged from transient vasospasm and nonobstructive presentations to plaque-related myocardial infarction, native-coronary thrombosis, and stent or graft thrombosis. Type I was the most frequently assigned phenotype. Allergological assessment, paired acute and baseline tryptase measurements, treatment chronology, and long-term follow-up were inconsistently reported. The main cardiovascular patterns remained broadly consistent across the planned sensitivity analyses. Food-associated KS encompasses a heterogeneous spectrum of allergic coronary presentations. Clinically similar non-immune food-related toxic reactions, including scombroid poisoning, should be recognized as differential diagnoses and analyzed separately from true allergic KS. Diagnosis requires integration of exposure chronology, objective cardiovascular findings, coronary substrate, allergological evidence, potential cofactors, and competing exposures. Intramuscular epinephrine remains the first-line treatment for anaphylaxis, and temporal precedence should not be interpreted as evidence that epinephrine caused the coronary event.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164551","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":"Ataxia-Telangiectasia, DNA Repair Deficits, Immune Dysfunction, and Cancer: A Review of Mechanisms, Clinical Presentations, and Emerging Therapies.","authors":"Birinder Singh Doad, Gustavo Borges, Yusheng Zhao, Danny Laurent, Susan Patricia Lees-Miller, Luis Murguía-Favela, Eyal Grunebaum, Aru Narendran","doi":"10.1007/s12016-026-09205-y","DOIUrl":"10.1007/s12016-026-09205-y","url":null,"abstract":"<p><p>Ataxia-Telangiectasia (A-T) is a rare, autosomal recessive disorder caused by biallelic pathogenic variants in the ATM gene. Loss of ataxia-telangiectasia mutated (ATM) protein function impairs DNA damage responses, leading to progressive neurodegeneration, genomic instability, immunodeficiency, and an increased risk of malignancy. Some A-T patients develop cancers at a young age and display extreme sensitivity to ionizing radiation and certain chemotherapeutics. Therefore, standard treatments often cause severe, life-threatening toxicities in these patients. This review discusses the dual role of ATM as a tumor suppressor and key DNA repair kinase, the mechanisms by which ATM deficiency promotes oncogenesis, and the unique challenges of treating malignancies in the context of A-T. We highlight emerging, less genotoxic therapies for ATM-deficient cancers including cancer vaccines, immune checkpoint inhibitors, CAR T-cell therapy, and synthetic lethal approaches such as Poly(ADP-ribose) polymerase (PARP) and Ataxia Telangiectasia and Rad3-related (ATR) inhibitors. These novel strategies may improve outcomes for A-T patients while minimizing treatment toxicity. We also outline future directions and clinical implications, emphasizing the need for tailored therapeutic approaches and multidisciplinary care for this high-risk population. Because prospective, A-T-specific therapeutic data are scarce, we draw extensively on the broader literature on somatic ATM-mutant cancers to inform management, while highlighting the additional constraints imposed by germline ATM loss.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105082","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":"Rethinking Monospecific Antibody Therapy in Chronic Rhinosinusitis with Nasal Polyps: Dual- and Multispecific Antibodies.","authors":"Yingying Dai, Tong Guo, Muhan Shi, Deyun Wang, Min Wang","doi":"10.1007/s12016-026-09200-3","DOIUrl":"https://doi.org/10.1007/s12016-026-09200-3","url":null,"abstract":"<p><p>Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disorder in which type 2 inflammation predominates but varies in its local organization, clinical context, and downstream tissue effects. Biologics targeting interleukin-4 receptor alpha, immunoglobulin E, the interleukin-5/interleukin-5 receptor axis, and thymic stromal lymphopoietin have expanded treatment options for severe disease and can improve polyp burden, nasal obstruction, olfactory function, quality of life, and corticosteroid- or surgery-related outcomes. However, responses remain variable across patients and clinical domains, and incomplete control may reflect target mismatch, persistent parallel inflammatory pathways, comorbid airway disease, or established tissue remodeling rather than insufficient pathway coverage alone. In this review, we summarize the mechanisms and clinical evidence for current monospecific antibodies and examine biological contexts that may contribute to variable treatment responses, including local IgE activity, microbial and antigenic amplification, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD), comorbid asthma, and persistent epithelial remodeling. We then discuss biomarkers, multidimensional response assessment, and clinical positioning of biologic therapy before evaluating the rationale, boundaries, molecular design, and current pipeline of dual- and multispecific antibodies. Attention is given to whether broader pathway targeting can provide incremental benefit over optimized monospecific therapy, while maintaining acceptable long-term safety, treatment practicality, and economic value. The future role of multispecific biologics in CRSwNP will depend on rational target pairing, comparative clinical evidence, and improved identification of patients most likely to benefit.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105044","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":"Beyond the Index Case: A Practical Framework for Cascade Family Screening in Hereditary Angioedema.","authors":"Gabriel Kc Leung, Andy Kc Kan, Philip H Li","doi":"10.1007/s12016-026-09206-x","DOIUrl":"https://doi.org/10.1007/s12016-026-09206-x","url":null,"abstract":"<p><p>Hereditary angioedema (HAE) is a genetic disorder characterised by recurrent cutaneous or submucosal oedema. Most cases are caused by pathogenic SERPING1 variants (types I and II), while a smaller subset presents with normal C1-inhibitor (C1-INH) levels and function (HAE-nC1INH). Despite its potentially life-threatening attacks, HAE remains under-diagnosed owing to inconsistent screening practices, low clinical awareness, poor patient acceptance, and resource limitations, resulting in diagnostic delays and preventable morbidity. Although international guidelines recommend family screening to identify at-risk relatives, no standardised protocol exists for its systematic implementation. Cascade family screening offers a structured approach to trace and test all known at-risk relatives across generations. Complementing this strategy, dried blood spot (DBS) assays provide a less invasive, cost-effective alternative to conventional serological testing, with particular utility in resource-limited settings. In this review, we critically appraise current screening methodologies, synthesise emerging evidence on cascade family screening and DBS-based diagnostics, and propose an actionable clinical flowchart to standardise identification, testing, and patient education from index case detection through multi-generational family screening.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105041","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":"Different Inflammatory Phenotypes and Immune Endotypes Drive Disease Heterogeneity in Asthma and COPD.","authors":"Cong Xie, Yaomin Jia, Xidan Kai, Weifeng Tang, Huijie Zhang, Congcong Li, Jian Cheng, Zhen Gao, Ying Wei, Maimaititusun Yalikun, Jingcheng Dong","doi":"10.1007/s12016-026-09204-z","DOIUrl":"10.1007/s12016-026-09204-z","url":null,"abstract":"<p><p>Asthma and chronic obstructive pulmonary disease (COPD) are highly heterogeneous airway disorders that cannot be adequately understood or managed as single disease entities. Instead, both encompass a wide spectrum of inflammatory phenotypes and immune endotypes that differ in pathobiological mechanisms, clinical presentation, exacerbation risk, and therapeutic responsiveness. In asthma, the classical type 2-high eosinophilic phenotype is typically driven by T helper 2 (Th2) cells, group 2 innate lymphoid cells (ILCs), and the canonical cytokines interleukin (IL)-4, IL-5, and IL-13, whereas non-type 2 asthma includes neutrophilic, mixed granulocytic, and paucigranulocytic patterns associated with Th17-related inflammation, epithelial dysfunction, and relative corticosteroid resistance. In COPD, neutrophil-dominant inflammation mediated by macrophages, Th1/Tc1 cells, and, in some patients, Th17-associated pathways has long been considered the dominant immunopathological pattern. However, growing evidence indicates that a substantial subset of patients with COPD exhibit eosinophil-associated, type 2-skewed inflammation with important implications for inhaled corticosteroid responsiveness and biologic therapy. In this review, we distinguish the concepts of phenotype and endotype, summarize the major inflammatory and immune subtypes of asthma and COPD, and discuss their underlying cellular and molecular mechanisms. We further examine clinically relevant biomarkers, including blood and sputum eosinophils, IgE, and fractional exhaled nitric oxide (FeNO), as well as the expanding therapeutic landscape encompassing anti-IgE, anti-IL-5, anti-IL-4Rα, anti-thymic stromal lymphopoietin (anti-TSLP), macrolides, phosphodiesterase-4 inhibitors, and emerging endotype-directed strategies. By comparing asthma and COPD within a unified immunological framework, this review highlights both shared and disease-specific mechanisms of heterogeneity and argues that mechanistically informed phenotyping and endotyping are central to advancing precision medicine in chronic airway disease.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036839","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":"Computational Approaches to Penicillin Allergy De-labelling: A Clinical Review.","authors":"Shuayb Elkhalifa, Jack Devey, Abdulrahaman Al-Asali, Haggar Elbashir, Maja Bulatović Ćalasan, Rick G Pleijhuis, Ingrid Terreehorst, Fulvio Salvo, Irfan Shafiq, Said Isse, Mohamed Abuzakouk, Mohamed Medhat Gaber, Rehan Bhana","doi":"10.1007/s12016-026-09203-0","DOIUrl":"10.1007/s12016-026-09203-0","url":null,"abstract":"<p><p>Penicillin allergy is recorded in roughly one in ten hospital patients, yet fewer than one in ten of those records reflects a real, clinically significant allergy. The mismatch matters: patients with a penicillin label receive more second-line and broader-spectrum antibiotics, with measurable downstream costs in infection, surgical site morbidity, length of stay, and antimicrobial resistance. Specialist-led skin testing and graded oral challenge remain the diagnostic standard, but the global allergy workforce cannot test the population that needs testing. Validated decision rules such as PEN-FAST, structured non-allergist pathways, and direct oral challenge in low-risk patients have closed part of that gap, but uptake is still limited by inconsistent free-text documentation, variable clinician confidence, and weak integration with electronic health records. This review summarises how computational methods are being added to that pathway. Supervised machine-learning models can mine electronic health records to identify candidates for review. Natural language processing can recover the timing, character, and severity of a reaction from clinic letters that the structured allergy field omitted. Predictive models that combine clinical, laboratory, and immunological inputs are starting to outperform rule-based scores on beta-lactam risk. Decision-support systems are moving past simple drug-name matching toward context-aware alerts. Image classifiers and large language models are opening a route to rapid, photograph-and-history triage. We discuss what is needed for any of this to be safe in routine care: representative training data, transparent model behaviour, regulatory alignment, and prospective evaluation against the outcomes the antimicrobial stewardship community already measures.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13597546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024180","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":"Gram-Positive and Gram-Negative Probiotic Extracellular Vesicles: Mechanisms of Immune Modulation and Therapeutic Opportunities in Atopic Dermatitis.","authors":"Vipul Wayal, Mey-Fann Lee, Jiu-Yao Wang, Yi-Hsing Chen","doi":"10.1007/s12016-026-09201-2","DOIUrl":"10.1007/s12016-026-09201-2","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease characterized by epidermal barrier dysfunction, type 2 immune skewing, and microbiome dysbiosis. Although live probiotics can modulate the gut-skin axis, their clinical use is limited by variable efficacy and safety concerns. Probiotic extracellular vesicles (PEVs) have emerged as cell-free nanotherapeutics that retain microbial bioactivity while circumventing the risks associated with live bacteria. However, the comparative immunological roles of vesicles from Gram-positive and Gram-negative probiotics remain incompletely understood. This review systematically compares Gram-negative outer membrane vesicles (OMVs) and Gram-positive membrane vesicles (MVs) in the context of AD. OMVs, enriched with lipopolysaccharide (LPS) and other bioactive cargo, mainly signal through toll-like receptor 4 (TLR4) to regulate innate immunity, strengthen antimicrobial defense, and modulate inflammation. In contrast, Gram-positive MVs, containing lipoteichoic acid (LTA), peptidoglycan (PG), proteins, and small RNAs, preferentially activate TLR2-linked pathways that support immune tolerance, regulatory T cell (Treg) responses, and barrier repair. Both PEV classes demonstrate significant potential in preclinical models by attenuating inflammation, improving epithelial integrity, and restoring microbiome balance. Despite this potential, clinical translation requires standardized isolation protocols, scalable manufacturing, rigorous safety testing, and regulatory alignment. Advances in microbial engineering and EV design may enable targeted, microbiota-directed therapies for AD.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13569578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944322","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}