Journal of Allergy and Clinical Immunology最新文献

{"title":"A Call to Standardize Exposure and Outcome Measures in Birth Cohort Studies on Asthma and Allergic Diseases.","authors":"James E Gern, Fernando D Martinez","doi":"10.1016/j.jaci.2025.01.043","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.043","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adulthood outcomes of thymic transplantation in a case of congenital athymia due to FOXN1 mutation.","authors":"Margarida Paulo-Pedro, Beatriz Moleirinho, Diana F Santos, André M C Gomes, Margarida Rei, Afonso R M Almeida, José G Marques, Susana L Silva, Ana E Sousa","doi":"10.1016/j.jaci.2025.02.006","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.006","url":null,"abstract":"<p><strong>Background: </strong>Defects of thymic stromal cell development may lead to congenital athymia and severe immunodeficiency. Allogeneic thymus transplantation is the only recognized effective therapy to reconstitute naïve T-cells in these rare cases, increasingly diagnosed due to worldwide newborn screening. Nevertheless, data on long-term outcomes are still missing.</p><p><strong>Objective: </strong>Report the clinical and immunological outcomes of an adult with R255X homozygous FOXN1 mutation, followed for 19 years upon thymus transplantation with effective immune reconstitution attested by clearance of BCG dissemination and reconstitution of the naïve T-cell compartment with a full-diverse repertoire.</p><p><strong>Methods: </strong>Longitudinal autoimmunity screening and immune profiling were complemented with T-cell studies by high-dimensional spectral flow cytometry (18 and 20 years-old) and single-cell RNA-sequencing (scRNA-seq, 18 years-old) combined with TCR and cell surface protein sequencing (CITE-seq) alongside age-matched controls.</p><p><strong>Results: </strong>The uneventful clinical report contrasted with the progressive decline of circulating T-cell counts (below 400 cells/μl), with marked contraction of the naïve compartment and lack of terminal differentiation. CD4 T-cells featured a unique transcriptional signature supporting a distinct biology of T-cells developed in an allogeneic thymus implant. Regulatory T-cells presented a suppressive signature, which may explain the absence of autoimmune manifestations. The expanded oligoclonal population of double-negative αβ T-cells identified before the transplant persisted with similar phenotype with transcriptional evidence of a role for the EGFR pathway in its maintenance.</p><p><strong>Conclusion: </strong>This rare case supports a distinct biology of T-cells educated in allogeneic thymus, with poor naïve T-cell sustainability emphasizing the need for research on immune reconstitution mechanisms.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoimmunity in Long-COVID.","authors":"Shubha Talwar, James A Harker, Peter J M Openshaw, Ryan S Thwaites","doi":"10.1016/j.jaci.2025.02.005","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.005","url":null,"abstract":"<p><p>Long-COVID (also termed Post-Acute Sequelae of SARS-CoV-2 or PASC) affects up to 10% of people recovering from SARS-CoV-2 infection. Diagnosis is hampered by diffuse symptomatology, lack of biomarkers, an incomplete understanding of pathogenesis, and the lack of validated treatments. In terms of pathogenesis, hypothesised causes include viral persistence, the legacy of endotheliitis and thrombosis, low-grade tissue-based inflammation and/or scarring, perturbation of the host virome/microbiome, or triggering of autoimmunity. Several studies show pre-existing and/or de novo production of autoantibodies after infection with SARS-CoV-2, but the persistence of these antibodies and their role in causing long-COVID is debated. Here, we review the mechanisms through which autoimmune responses can arise during and after viral infection, focusing on the evidence for B-cell dysregulation and autoantibody production in acute and long-COVID.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating Large Language Model Performance to Support the Diagnosis and Management of Patients with Primary Immune Disorders.","authors":"Nicholas L Rider, Yingya Li, Aaron T Chin, Daniel V DiGiacomo, Cullen Dutmer, Jocelyn R Farmer, Kirk Roberts, Guergana Savova, Mei-Sing Ong","doi":"10.1016/j.jaci.2025.02.004","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.004","url":null,"abstract":"<p><strong>Background: </strong>Generative artificial intelligence (GAI) is transforming healthcare in a variety of ways; however, present utility of GAI for supporting clinicians in rare disease such as primary immune disorders (PI) is not well studied. Here we evaluate the ability of 6 state-of-the-art large language models (LLMs) for providing clinical guidance about PI.</p><p><strong>Objective: </strong>We sought to quantitatively and qualitatively measure the utility of current, open-source LLMs for diagnosing and providing helpful clinical decision support about PI.</p><p><strong>Methods: </strong>Five expert clinical immunologists provided 5 real-world (n=25), anonymized PI case vignettes via multi-turn prompting to 6 LLMs (OpenAI GPT-4o, Llama-3.1-8B-Instruct, Llama-3.1-70B-Instruct, Mistral-7B-Instruct-v0.3, Mistral-Large-Instruct-2407, and Mixtral-8x7B-Instruct-v0.1). We assessed the diagnostic accuracy of the LLMs and the quality of clinical reasoning using the Revised-IDEA (R-IDEA) score. Qualitative LLM assessment was made by immunologist narratives.</p><p><strong>Results: </strong>Performance accuracy (>88%) and R-IDEA scores (>=8) were superior for 3 models (GPT-4o, Llama-3.1-70B-Instruct, Mistral-Large-Instruct-2407), with GPT-4o achieving the highest diagnostic accuracy (96.2%). Conversely, the remaining 3 models fell below acceptable accuracy rates near 60% or worse and poor R-IDEA scores (<=0.55), with Mistral-7B-Instruct-v0.3 attaining the worst diagnostic accuracy (42.3%). Compared with the 3 best-performing LLMs, the 3 worst-performing LLMs received a substantially lower median R-IDEA score (p<0.001). Interclass correlation coefficient for R-IDEA score assignments varied substantially by LLM, ranging from good to poor agreement, and did not appear to correlate with either diagnostic accuracy or the median R-IDEA score. Qualitatively, immunologists identified several themes (e.g. correctness, differential diagnosis appropriateness, relative conciseness of explanations) of relevance to PI.</p><p><strong>Conclusions: </strong>LLM can support the diagnosis and management of PI; however, further tuning is needed to optimize LLMs for best practice recommendations.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Opportunities in AI/ML to Endotype Asthma and Other Eosinophilic Diseases.","authors":"Anuradha Ray, Jishnu Das, Paneez Khoury","doi":"10.1016/j.jaci.2025.01.044","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.044","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement and fungal diseases.","authors":"Jigar V Desai, Michail S Lionakis","doi":"10.1016/j.jaci.2025.02.003","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.003","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tezepelumab for the Treatment of Chronic Spontaneous Urticaria: Results of the Phase 2b INCEPTION Study.","authors":"Julie McLaren, Yun Chon, Kevin S Gorski, Jonathan A Bernstein, Jonathan Corren, Koremasa Hayama, Vipul Jain, Hermenio Lima, Howard Sofen, Sandhia Ponnarambil, Nestor A Molfino, Marcus Maurer","doi":"10.1016/j.jaci.2025.01.045","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.045","url":null,"abstract":"<p><strong>Background: </strong>Tezepelumab, a monoclonal antibody inhibiting thymic stromal lymphopoietin (TSLP), is an upstream-targeted therapy with potential to inhibit multiple pathways in chronic spontaneous urticaria (CSU).</p><p><strong>Objective: </strong>To evaluate tezepelumab efficacy and safety in CSU patients despite sgAH treatment.</p><p><strong>Methods: </strong>This phase 2b study randomized 183 patients (125 anti-IgE therapy-naïve; 58 anti-IgE therapy-experienced) to placebo Q2W, tezepelumab 210 mg Q4W, tezepelumab 420 mg Q2W, or omalizumab 300 mg Q4W (anti-IgE-naïve only) for 16-week treatment. The primary endpoint was change from baseline in UAS7 at week 16. Safety and exploratory endpoints were evaluated through week 32.</p><p><strong>Results: </strong>The 16-week primary endpoint was not met: In the overall population, tezepelumab 210 mg and 420 mg did not significantly improve UAS7 versus placebo (LSM [SE]: -13.5 [1.6] and -14.7 [1.5], respectively, vs -13.6 [1.6], p = 0.99, nominal and p = 0.60, nominal, respectively). Greater improvement in UAS7 versus placebo was observed in the anti-IgE-naïve tezepelumab-treated populations (nominal significance); a trend toward significance was observed with omalizumab. In the anti-IgE-naïve population there was delayed, sustained, 32-week off-treatment improvement in UAS7 versus placebo with tezepelumab 210 mg (nominally significant) and 420 mg (trend), but not with omalizumab. This effect was larger in patients with lower baseline IgE levels and longer CSU duration and accompanied sustained IL-5 and IL-13 reductions. Tezepelumab and placebo safety findings were balanced.</p><p><strong>Conclusion: </strong>Although the 16-week primary endpoint was not met, tezepelumab showed post-treatment reductions in CSU activity through week 32, suggesting a delayed, sustained, TSLP blockade treatment effect.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Getting to know ADA2 deficiency inside and out.","authors":"Lisa Ehlers, Isabelle Meyts","doi":"10.1016/j.jaci.2025.01.040","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.040","url":null,"abstract":"<p><p>Ten years after the description of the first cohorts of patients with ADA2 deficiency (DADA2), the pathomechanisms underlying the disease on a cellular level remain poorly understood. With the establishment of the lysosomal localization of the ADA2 protein and its involvement in nucleic acid sensing, the pathophysiological focus has shifted to the inside of the cell. At the same time, extracellular (serum) ADA2 enzyme activity continues to be the diagnostic gold standard in patients with suspected DADA2. The diverse clinical phenotype and weak genotype-phenotype correlations further complicate the identification of shared cellular mechanisms that cause inflammation, immunodeficiency as well as bone marrow failure in the absence of functional ADA2. This review inspects the characteristics of the ADA2 protein and its proposed function. The latter is discussed in the context of possible mechanisms driving the clinical phenotype in patients lacking functional ADA2. We discuss established processes and introduce unexplored pathways in the pathogenesis of DADA2.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is dupilumab use in atopic dermatitis associated with cutaneous T cell lymphoma?","authors":"Peck Y Ong","doi":"10.1016/j.jaci.2025.02.002","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.002","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum.","authors":"","doi":"10.1016/j.jaci.2025.02.001","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.001","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}