Clinical Reviews in Allergy & Immunology最新文献

{"title":"Neurological Complications in Inborn Errors of Immunity: A Scoping Review of Clinical Spectrum, Pathophysiological Mechanisms, and Therapeutic Strategies.","authors":"Ningkun Xiao, Xinlin Huang, Linzi Chen, Wanli Zang, Maosen Guan, Tianjiao Li, Irina Tuzankina, Valery Chereshnev, Guojun Liu","doi":"10.1007/s12016-025-09078-7","DOIUrl":"https://doi.org/10.1007/s12016-025-09078-7","url":null,"abstract":"<p><p>Inborn errors of immunity (IEIs) are traditionally viewed as monogenic disorders of the immune system, but mounting evidence indicates that they often have underappreciated impacts on the nervous system. We review the emerging intersection between IEIs and neurological diseases, spanning neurodevelopmental and neurodegenerative manifestations. We discuss how genetic overlaps between immunity and brain development-for example, defects in DNA repair, chromatin remodeling, or cytokine signaling-can lead to combined immunological and neurological phenotypes. Clinical data from patient cohorts highlight that a substantial subset of IEIs present with neurodevelopmental disorders (such as autism spectrum disorder, intellectual disability, or ADHD) and/or neurodegenerative diseases (such as progressive ataxia, motor regression, or cognitive decline). These comorbidities arise through diverse mechanisms, including direct roles of immune genes in neural development, the impact of chronic inflammation on the brain, and metabolic byproducts toxic to neural tissue. We illustrate these mechanisms with examples such as ataxia-telangiectasia (a DNA repair defect causing immunodeficiency and cerebellar degeneration) and DiGeorge syndrome (a developmental immunodeficiency often initially diagnosed as autism). The translational importance of these insights is profound-recognizing neurological involvement in IEIs can improve early diagnosis and multidisciplinary care, whereas a deeper understanding of immune-neural crosstalk opens avenues for novel therapies (such as targeted anti-inflammatory treatments or gene therapies that address both immune and neural dysfunction). By integrating immunology and neuroscience perspectives, this comprehensive review sheds light on the immune underpinnings of certain neurologic diseases and underscores the importance of collaborative management for patients at this complex interface.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"67"},"PeriodicalIF":8.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667249","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 c.64 + 2 T > A Founder Variant Hits Home: Report on 14 Patients Expands the Phenotypic Landscape of Inherited ARPC1B Deficiency - a Comparative Analysis.","authors":"Dharmagat Bhattarai, Aaqib Zaffar Banday, Pratap Kumar Patra, Ramji Baral, Chakshu Chaudhry, Katta M Girisha, Jolan E Walter, Ganga Narasimhan, Bénédicte Neven, Asbjørg Stray-Pedersen, Kathleen E Sullivan","doi":"10.1007/s12016-025-09070-1","DOIUrl":"https://doi.org/10.1007/s12016-025-09070-1","url":null,"abstract":"<p><strong>Background: </strong>Inherited ARPC1B deficiency (ARPC1BD) is a rare autosomal recessive inborn error of immunity that manifests with allergic, infective, and autoimmune/inflammatory features. Only about three dozen patients with ARPC1BD have been reported in the literature thus far.</p><p><strong>Methods: </strong>We describe 14 patients (ten families) with ARPC1BD from Nepal. Many of these patients have unique/rare clinical features that expand the phenotypic spectrum of ARPC1BD. The study included data on clinical-epidemiological features, immuno-hematological parameters, treatment, and outcome. Homozygosity mapping and haplotype analysis were used to evaluate the founder effect.</p><p><strong>Results: </strong>We noted allergic/autoimmune and infective manifestations in all of our patients. Notable clinical features noted in our study include rheumatoid factor positive (RF+) chronic arthritis (mimicking RF+ juvenile idiopathic arthritis), significantly elevated anti-tissue transglutaminase antibody titers, generalized skin hyperpigmentation, distal phalangeal enlargement, frontal bone hypertrophy, hypertrophic skin scars, and hyperkeratosis. All cases harbored the founder splice-site variant c.64+2T>A in the ARPC1B gene. Long-term outcomes in our patients appeared worse than reported previously. Comparative phenotypic analysis showed significantly greater proportions of otitis, gastroenteritis, inflammatory bowel disease-like manifestations, and elevated IgA in patients with c.64+2T>A variant as compared to other variants. Homozygosity mapping (in eight probands) revealed that the gene/variant is contained within the only overlapping region of homozygosity (>1 Mb) across all autosomal chromosomes. Besides, the included probands share a similar haplotype around the said variant.</p><p><strong>Conclusions: </strong>c.64+2T>A is a founder variant in Nepalese patients with ARPC1BD. This variant is associated with a severe clinical phenotype and diverse clinical complications.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"64"},"PeriodicalIF":8.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641974","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 beyond Eczema: A Review on its Systemic Impact through Pruritus and Associated Comorbidities.","authors":"Alvaro Prados-Carmona, Husein Husein-ElAhmed, Francisco J Navarro-Triviño, Ricardo Ruiz-Villaverde","doi":"10.1007/s12016-025-09075-w","DOIUrl":"https://doi.org/10.1007/s12016-025-09075-w","url":null,"abstract":"<p><p>Atopic dermatitis is the most prevalent chronic inflammatory skin disease, traditionally recognized for its defining eczematous lesions. However, the implications of atopic dermatitis extend far beyond eczema itself. Increasing understanding of the disease has enabled a more accurate characterization of its burden, including structural and functional skin alterations as well as various systemic comorbidities. This review examines the impact of the disease, beginning with the neuroimmune pathways underlying pruritus and its psychosocial burden, and progressing to the current concepts surrounding the atopic march and the broader spectrum of inflammatory or immune-mediated non-atopic comorbidities, including the emerging discussion on its similarities and differences with psoriasis. Special attention has been given to literature published from 2015 onwards. Ultimately, this review aims to deepen the understanding of the systemic nature of atopic dermatitis, providing a broader conceptual framework for assessing disease extent and severity.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"66"},"PeriodicalIF":8.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641973","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":"Advances in Shellfish Allergy Therapy: From Current Approaches to Future Strategies.","authors":"Sahel Heidari, Thimo Ruethers, Shaymaviswanathan Karnaneedi, Lydia Wong Su Yin, Andreas Ludwig Lopata","doi":"10.1007/s12016-025-09077-8","DOIUrl":"10.1007/s12016-025-09077-8","url":null,"abstract":"<p><p>Shellfish allergy, triggered by immune reactions to crustacean and mollusk proteins upon consumption/inhalation, is one of the most severe and persistent food allergies, affecting approximately 1%-3% of the general population worldwide. Shellfish is among the \"big nine\" food allergens responsible for over 90% of food allergy cases worldwide. Its diagnosis poses major challenges due to regional species diversity and a lack of reliable diagnostic tools. Management strategies generally emphasize strict avoidance and provision of emergency adrenaline autoinjectors; however, these approaches are inconvenient and insufficient for both patients and healthcare providers. Given the rising prevalence of shellfish allergy, there is an urgent need for targeted therapies that focus on key allergens, particularly tropomyosin-a major pan-allergen. As the primary target in current immunotherapy approaches, tropomyosin plays a central role in driving shellfish-induced immune responses. Recent advancements in immunotherapy are exploring alternatives beyond avoidance, aiming for long-term desensitization. This review discusses progress with allergen-specific immunotherapy, hypoallergenic allergen variants, DNA-based vaccines, and innovative approaches involving immunoregulatory peptides and probiotics. These strategies collectively strive to desensitize patients, reduce allergic symptoms, and enhance quality of life. Although some therapies are in active trials, most are in the investigational stages and offer promising directions for effective, patient-centered long-term management of shellfish allergy.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"65"},"PeriodicalIF":8.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641972","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":"The Treatment of Primary Biliary Cholangitis: Time for Personalized Medicine.","authors":"Xinyi Men, Yansheng Liu, Han Zhao, Bingrui Xie, Changcun Guo, Patrick S C Leung, Suraj Timilsina, M Eric Gershwin, Yulong Shang, Ying Han","doi":"10.1007/s12016-025-09074-x","DOIUrl":"10.1007/s12016-025-09074-x","url":null,"abstract":"<p><p>Primary Biliary Cholangitis is an autoimmune liver disease distinguished by Anti-mitochondrial Antibodies and chronic non-suppurative lymphocytic microcholangitis. UDCA remains the exclusively recommended initial therapy for PBC. However, 40% of patients experience either incomplete biochemical response or intolerance to UDCA, which represents poorer outcomes and increased mortality. Therefore, early identification of high-risk patients and timely intensive treatments are necessary to delay the progression of PBC and better improve the prognosis. Intensive therapeutic strategies based on more stringent treatment goals and early efficacy assessment criteria are elaborated in this review. To exclude AIH-PBC overlap syndrome, liver biopsy is required for cholestasis patients with negative AMAs or PBC patients who respond inadequately to UDCA, especially those with elevated ALT and IgG. Combined immunosuppressants are considered for patients with moderate-to-severe hepatitis. ALP normalization is considered the improved therapeutic goal for high-risk patients, which has been verified achievable in multiple treatment attempts. The control of pruritus and fatigue constitutes the key therapeutic targets in the symptom management of PBC. Bezafibrate, Seladelpar, and IBAT inhibitors have demonstrated significant therapeutic potential in pruritus. Last but not least, Liver Stiffness Measurement is substantiated as efficient in the fibrotic monitoring of PBC patients. OCA and fibrates are respectively useful for compensated and decompensated fibrotic patients. Moreover, the conventional efficacy assessment procedure, which is the \"wait-to-fail\" strategy, exhibits suboptimal sensitivity in the timely detection of treatment-responsive patients. Therefore, early prediction and evaluation criteria at baseline and 1-month treatment will help in timely interventions for patients with insufficient efficacy. This improved identification strategy is expected to provide precise and personalized treatment for PBC patients.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"63"},"PeriodicalIF":8.4,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616622","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":"Integrating Machine Learning into Myositis Research: a Systematic Review.","authors":"Christian Juarez-Gomez, Andrea Aguilar-Vazquez, Emiliano Gonzalez-Gauna, Gabriela Paola Garcia-Ordoñez, Beatriz Teresita Martin-Marquez, Cynthia-Alejandra Gomez-Rios, Jose Becerra-Jimenez, Arahi Gaspar-Ruiz, Monica Vazquez-Del Mercado","doi":"10.1007/s12016-025-09076-9","DOIUrl":"10.1007/s12016-025-09076-9","url":null,"abstract":"<p><p>Idiopathic inflammatory myopathies (IIM) are a group of autoimmune rheumatic diseases characterized by proximal muscle weakness and extra muscular manifestations. Since 1975, these IIM have been classified into different clinical phenotypes. Each clinical phenotype is associated with a better or worse prognosis and a particular physiopathology. Machine learning (ML) is a fascinating field of knowledge with worldwide applications in different fields. In IIM, ML is an emerging tool assessed in very specific clinical contexts as a complementary tool for research purposes, including transcriptome profiles in muscle biopsies, differential diagnosis using magnetic resonance imaging (MRI), and ultrasound (US). With the cancer-associated risk and predisposing factors for interstitial lung disease (ILD) development, this systematic review evaluates 23 original studies using supervised learning models, including logistic regression (LR), random forest (RF), support vector machines (SVM), and convolutional neural networks (CNN), with performance assessed primarily through the area under the curve coupled with the receiver operating characteristic (AUC-ROC).</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"62"},"PeriodicalIF":8.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583255","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":"Towards a Multi-omics Understanding of Anaphylaxis: Insights into Pathogenesis and Biomarker Identification.","authors":"Manca Svetina, Tanja Kunej, Peter Korošec, Matija Rijavec","doi":"10.1007/s12016-025-09069-8","DOIUrl":"10.1007/s12016-025-09069-8","url":null,"abstract":"<p><p>Anaphylaxis is a severe, life-threatening hypersensitivity reaction that presents significant challenges in both clinical practice and scientific research. While individual omics studies have provided valuable insights into the genetic predisposition, immune dysregulation, and metabolic alterations associated with anaphylaxis, a comprehensive understanding of its full pathophysiology remains elusive. Multi-omics integration, which combines genomics, epigenomics, transcriptomics, proteomics, and metabolomics, has the potential to uncover novel mechanisms, biomarkers, and therapeutic targets. However, studies employing comprehensive multi-omics approaches in anaphylaxis are still limited. This review of 107 studies published between 2000 and 2024-including genomics (43), metagenomics (2), epigenomics (2), transcriptomics (20), proteomics (26), and metabolomics (14)-synthesizes findings from existing single-omics studies on human anaphylaxis, identifies key interconnections across omics layers, and underscores the critical need for large-scale, integrative research. Advancing this type of research is essential to advance our understanding of anaphylaxis, improve risk prediction, and enhance both diagnosis and treatment strategies.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"61"},"PeriodicalIF":8.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526698","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":"Aberrant Activation of Mast Cells: Molecular Mechanisms and Targets for Intervention.","authors":"Jinghao Wen, Zehao Lan, Liting He, Hai Long","doi":"10.1007/s12016-025-09065-y","DOIUrl":"10.1007/s12016-025-09065-y","url":null,"abstract":"<p><p>Mast cells play a key role in innate immunity by mediating host defense and maintaining tissue balance. They achieve this through the controlled release of bioactive mediators such as histamine, heparin, leukotrienes, and prostaglandin D2. Their functional diversity is enabled by multiple receptor systems that coordinate differentiation, maturation, and degranulation processes through tissue-specific microenvironmental signals. Pathological activation through allergen exposure or intrinsic regulatory dysfunction contributes to various disorders, ranging from allergic conditions to autoimmune diseases and chronic inflammatory states. Current anti-mast cell therapies have expanded from broad-spectrum antihistamines to more precise treatments targeting IgE or its surface receptors expressed on mast cells. Emerging insights into activation mechanisms of mast cells, particularly structural and functional characterization of critical receptors, have accelerated the development of novel therapeutic interventions. This review discusses the advances in molecular mechanisms of mast cell activation and summarizes how these findings redefine our understanding of disease progression and emerging therapeutic targets.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"60"},"PeriodicalIF":8.4,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336380","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":"Current Understanding of Epithelial-Derived Alarmins in Chronic Rhinosinusitis with Nasal Polyps.","authors":"Fuying Cheng, Yizhang Wang, Yingqi Gao, Chen Zhang, Qianqian Zhang, Jiani Chen, Yumin Zhou, Le Shi, Li Hu, Huan Wang, Yaguang Zhang, Xicai Sun","doi":"10.1007/s12016-025-09073-y","DOIUrl":"https://doi.org/10.1007/s12016-025-09073-y","url":null,"abstract":"<p><p>Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory condition characterized by persistent sinus inflammation and tissue remodeling. Epithelial-derived alarmins, including thymic stromal lymphopoietin (TSLP), interleukin-33 (IL-33), and interleukin-25 (IL-25), are critical mediators that initiate and amplify immune responses in CRSwNP. These alarmins are secreted by stressed or damaged nasal epithelial cells in response to environmental insults, such as allergens, microbial infections, pollutants, and proteases. Once released, they orchestrate immune cell activation and amplify inflammatory pathways. Targeting epithelial-derived alarmins has emerged as a promising therapeutic strategy for CRSwNP, with several biologics, including TSLP and IL-33 inhibitors, showing encouraging clinical outcomes. This review focuses on the role of epithelial-derived alarmins in CRSwNP, examining their expression patterns, regulatory mechanisms, and contributions to inflammation, evaluating the current progress in alarmin-targeted therapies, and exploring future research directions to optimize their clinical application.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"59"},"PeriodicalIF":8.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324648","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 Findings on the Development and Immunological Functions of Palatine Tonsils.","authors":"Nadiya Abulikemu, Zheng Liu, Yang Liu","doi":"10.1007/s12016-025-09071-0","DOIUrl":"https://doi.org/10.1007/s12016-025-09071-0","url":null,"abstract":"<p><p>The palatine tonsils, positioned at the aerodigestive crossroads, serve as immunological sentinels orchestrating frontline defense through coordinated surveillance of inhaled and ingested antigens. As secondary lymphoid organs, palatine tonsils bridge innate and adaptive immunity via specialized microanatomical domains. Recent paradigm shifts now position the tonsils as dual-function immunological entities: while essential for pathogen surveillance and mucosal immunity, their dysregulated immune responses may paradoxically drive systemic inflammation. Concurrently, emerging evidence demonstrates therapeutic implications of tonsillar modulation, particularly through precision interventions such as tonsillectomy. This review examines recent advances in tonsillar anatomy and histology while critically evaluating novel insights into their pathogenic involvement in autoimmune diseases and other extra-tonsillar disorders. Furthermore, we analyze evolving perspectives on tonsil-targeted therapies as potential disease-modifying strategies. The synthesis underscores the tonsils' evolving status from regional lymphoid tissue to systemic immunomodulatory organ, bridging mucosal defense mechanisms with systemic inflammatory pathogenesis.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"68 1","pages":"58"},"PeriodicalIF":8.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324649","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}