Journal of Allergy and Clinical Immunology最新文献

{"title":"Long-COVID - pathophysiology, current concepts and future directions.","authors":"Chrysanthi Skevaki,Charalampos D Moschopoulos,Paraskevi C Fragkou,Karsten Grote,Elisabeth Schieffer,Bernhard Schieffer","doi":"10.1016/j.jaci.2024.12.1074","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.12.1074","url":null,"abstract":"Long-COVID, an umbrella term referring to a variety of symptoms and clinical presentations, which emerge in a subset of patients after SARS-CoV-2 infection, has a significant impact on an individual's quality of life and places a substantial burden on healthcare systems worldwide, straining financial and human resources. The pathophysiology of long-COVID remains incompletely understood, though several hypotheses have been proposed to explain different aspects of this complex condition. SARS-CoV-2 persistence, direct organ damage, innate and adaptive immune system pertubation, autoimmunity, latent viruses reactivation, endothelial dysfunction, and microbiome disturbances are among the most relevant avenues for elucidating the evolution, complexity, and mechanisms of long-COVID. Active investigation regarding potential biomarkers for long-COVID and its associated disease endotypes highlights the role of inflammatory mediators, immunophenotyping and multi-omics approaches. Further advances in understanding long-COVID are needed to inform current and future therapeutics.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"160 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887521","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":"DOCK8 at the crossroads of immunodeficiency and hyperinflammation.","authors":"Casey A Rimland, Michael T Lam, Pui Y Lee","doi":"10.1016/j.jaci.2024.12.1072","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.12.1072","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882109","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":"Novel Diagnostics in Food Allergy.","authors":"Holly Boyd, Alexandra F Santos","doi":"10.1016/j.jaci.2024.12.1071","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.12.1071","url":null,"abstract":"<p><p>Food allergy is increasing in prevalence, and poses significant challenges for individuals and their families, adversely impacting their quality of life. Misdiagnosis can lead to unnecessary dietary and social limitations, and increased food allergy risk, while failure to diagnose may result in life-threatening anaphylaxis. Therefore, a precise diagnosis is of the utmost importance; however, barriers exist at every stage of the diagnostic process. Food allergy diagnosis relies on clinical history, IgE sensitization tests, and oral food challenges. Component testing and identification of optimal cut-offs have improved diagnostic accuracy. Nevertheless, many patients still require oral food challenges and better tests are needed to reduce this. Novel biomarkers, such as the basophil activation test and peptide IgE testing, are transitioning into clinical practice. Future approaches may include alternative biological samples, novel laboratory technologies, and analytical tools, including artificial intelligence, to integrate test results and clinical information. Conscientious use of existing tests, access to tests with superior diagnostic accuracy and combination of tests, can lead to improved precision of food allergy diagnosis and timely introduction of tolerated foods in the diet. This review summarizes recent advances in novel approaches for food allergy diagnosis that can enhance clinical decision-making, now and in the future.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876985","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":"Imaging eosinophil secretory granules: From storage containers to active, immune responder organelles.","authors":"Rossana C N Melo, Marc E Rothenberg","doi":"10.1016/j.jaci.2024.12.1069","DOIUrl":"10.1016/j.jaci.2024.12.1069","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870840","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":"New Frontiers in Asthma Chest Imaging.","authors":"Alexander M Matheson, Joseph Johnstone, Peter J Niedbalski, Jason C Woods, Mario Castro","doi":"10.1016/j.jaci.2024.12.1067","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.12.1067","url":null,"abstract":"<p><p>Modern pulmonary imaging can reveal underlying pathological and pathophysiological changes in the lungs of people with asthma, with important clinical implications. A multitude of imaging modalities are now used to examine underlying structure/function relationships including computed tomography, magnetic resonance imaging, optical coherence tomography, and endobronchial ultrasound. Imaging-based biomarkers from these techniques, including airway dimensions, blood vessel volumes, mucus scores, ventilation defect extent and air trapping extent, often have increased sensitivity compared to traditional lung function measurements, and are increasingly used as endpoints in clinical trials. Imaging has been crucial to recent improvements in our understanding of relationships between T2-inflammation, eosinophilia, and mucus extent. With the advent of effective anti-T2 biologic therapies, computed tomography and magnetic resonance imaging techniques can identify not just which patients benefit from therapy, but why they benefit. Clinical trials have begun to assess the utility of imaging to prospectively plan airway therapy targets in bronchial thermoplasty and have potential to direct future bronchoscopic therapies. Together, imaging techniques provide a diverse set of tools to investigate how spatially-distributed airway, blood, and parenchymal abnormalities shape disease heterogeneity in patients with asthma.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871228","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":"Single-cell RNA sequencing of chronic idiopathic erythroderma defines disease-specific markers.","authors":"Sumanth Chennareddy, Katharina Rindler, Shannon Meledathu, Malini P Naidu, Natalia Alkon, John R Ruggiero, Lisa Szmolyan, Wolfgang Weninger, Wolfgang M Bauer, Johannes Griss, Constanze Jonak, Patrick M Brunner","doi":"10.1016/j.jaci.2024.11.037","DOIUrl":"10.1016/j.jaci.2024.11.037","url":null,"abstract":"<p><strong>Background: </strong>Chronic erythroderma is a potentially life-threatening condition that can be caused by various diseases, but approximately 30% of cases remain idiopathic, often with insufficient treatment options.</p><p><strong>Objective: </strong>We sought to establish a molecular disease map of chronic idiopathic erythroderma (CIE).</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing combined with T-cell receptor sequencing of blood and skin from 5 patients with CIE and compared results with 8 cases of erythrodermic cutaneous T-cell lymphoma (eCTCL), 15 cases of moderate to severe atopic dermatitis, 10 cases of psoriasis, and 20 healthy control individuals.</p><p><strong>Results: </strong>In eCTCL, we found strong expansion of CD4⁺ malignant clones with a CCR7⁺SELL⁺ central memory phenotype. In contrast, CIE exhibited a pattern of low-level, but consistent, expansion of CD8A⁺KLRK1⁺ T-cell clones, both in blood and in skin. KLRK1 was also expressed by CCR10⁺FUT7⁺ skin-homing CIE blood T cells that had increased proliferation rates and were absent in all other conditions. While patients with CIE and eCTCL lacked the strong type 2 or type 17 immune skewing typically found in atopic dermatitis or psoriasis, respectively, they were characterized by upregulation of MHC II genes (HLA-DRB1, HLA-DRA, and CD74) in keratinocytes and fibroblasts, most likely in an IFN-γ-dependent fashion. Overall, we found the strongest upregulation of type 1 immune mediators in CIE samples, both in the expanded CD8A⁺ clones and in the tissue microenvironment.</p><p><strong>Conclusions: </strong>Despite the notion that CIE might be a mere bundle of various yet uncharacterized disease processes, we found specific pathogenic signatures in these patients, which were different from other forms of erythroderma. These data might help to improve our pathogenic understanding of the blood and skin compartments of CIE, aiding in discovery of future treatment targets.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854262","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":"Successful hematopoietic cell transplantation utilizing myeloablative reduced-toxicity conditioning in Chediak-Higashi syndrome.","authors":"Alan Bidgoli, Binni Kunvarjee, Andromachi Scaradavou, Richard J O'Reilly, Jaap Jan Boelens, Susan E Prockop, Joseph H Oved","doi":"10.1016/j.jaci.2024.11.014","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.014","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846791","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":"Clinical response and corresponding blood transcriptome pathways before and after treatment of hereditary angioedema prodromes compared to active swelling attacks.","authors":"Debajyoti Ghosh, John Anderson, Umesh Singh, Cheryl K Bernstein, Jonathan A Bernstein","doi":"10.1016/j.jaci.2024.11.035","DOIUrl":"10.1016/j.jaci.2024.11.035","url":null,"abstract":"<p><strong>Background: </strong>Approximately 85% of hereditary angioedema (HAE) attacks are associated with prodromal symptoms.</p><p><strong>Objective: </strong>We investigated the clinical effect of treating HAE C1-esterase inhibitor (HAE-C1-INH) type 1 patients with recombinant human C1-INH (rhC1-INH) during their prodrome versus an active swelling episode and associated changes in blood transcriptomic genes and pathways before and after treatment.</p><p><strong>Methods: </strong>A 2-center, unblinded, case-crossover study randomly assigned 5 HAE-C1-INH type 1 patients to prodrome or attack treatment groups; after a patient was treated for either 2 prodromes or 2 HAE attacks, they were crossed over to be treated for 2 HAE attacks or 2 prodromes. All patients were treated during the prodrome or acute attack with rhC1-INH; (conestat alfa, 50 IU/kg body weight, maximum 4200 IU for body weight ≥85 kg). Blood samples for analysis by RNA sequencing were obtained (1) at baseline, (2) during the prodrome before and after treatment, and (3) during an attack before and after treatment. Differentially expressed genes and pathways were elucidated by Ingenuity Pathway Analysis (IPA; Qiagen).</p><p><strong>Results: </strong>Treatment during the HAE prodrome with rhC1-INH was as effective at preventing progression to a swelling episode as treatment of an acute attack. HAE prodromes were associated with upregulation of multiple inflammatory extracellular matrix genes, neuropeptide, and inflammasome member genes (eg, SPARCL1, AGRP, NLRP9; log₂ fold change = 4.1, 3.9, and 3.0, respectively). TNF-α and IL-10 were 2 major hub genes in prodrome-associated enriched gene networks. rhC1-INH treatment resulted in reversal of the disease signature in HAE-associated dysregulated pathways. Approximately 42% of prodrome-associated differentially expressed genes were also associated with HAE attacks. The enriched gene networks with hub genes for prodrome (ERK and VEGF) and for acute attack (insulin and SERPINA1) stages of HAE were identified. The major enriched pathways shared between HAE prodrome and attack were associated with neutrophil function and prostaglandin metabolism.</p><p><strong>Conclusion: </strong>Treatment of HAE-C1-INH type 1 patients who have a well-defined prodrome that historically results in an acute attack may be justified clinically and mechanistically. This approach would represent a paradigm shift for management of HAE on-demand treatment.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828271","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":"Chimeric antigen receptor-modified T-cell therapy: Recent updates and challenges in autoimmune diseases.","authors":"Blandine Caël, Elodie Bôle-Richard, Francine Garnache Ottou, François Aubin","doi":"10.1016/j.jaci.2024.12.1066","DOIUrl":"10.1016/j.jaci.2024.12.1066","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T-cell therapy (CAR-T) has revolutionized the treatment of hematologic malignancies, demonstrating significant clinical efficacy and leading to US Food and Drug Administration approval of several CAR T-cell-based products. This success has prompted exploration of CAR-T in other disease areas, including autoimmune diseases (AIDs). CAR-T targeting B cells has been shown to provide clinical and biological improvements in patients with refractory AIDs. The aim of this review is to discuss promising strategies involving CAR-T in AIDs, such as those targeting B cells and T cells, and to explore new approaches targeting fibroblasts or plasmacytoid dendritic cells. Despite these advances, the application of CAR-T in AIDs faces several unique challenges. The quality and functionality of T cells in patients with AIDs may be compromised as a result of previous treatments and the underlying inflammatory state, affecting the generation and efficacy of CAR-T. In addition, achieving adequate tissue biodistribution and persistence of CAR T cells in affected tissues remains a major challenge. Finally, the high costs associated with T-cell production pose economic problems, particularly in the context of chronic diseases, which are far more numerous than the hematologic diseases for which CAR-Ts have been granted marketing authorization to date. If the indications for CAR-T increase significantly, production costs will have to drop drastically in order to obtain reliable economic models.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828829","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":"Mortality in adult patients with chronic spontaneous urticaria: A real-world cohort study.","authors":"Pavel Kolkhir, Katja Bieber, Tomasz Hawro, Khalaf Kridin, Marlene A Ludwig, Henning Olbrich, Martin Metz, Artem Vorobyev, Ralf J Ludwig, Marcus Maurer","doi":"10.1016/j.jaci.2024.11.036","DOIUrl":"10.1016/j.jaci.2024.11.036","url":null,"abstract":"<p><strong>Background: </strong>Chronic spontaneous urticaria (CSU), a common and debilitating disease, is widely held not to be life limiting, but the mortality of CSU has not been investigated.</p><p><strong>Objective: </strong>We sought to assess all-cause mortality in patients with CSU, risk for comorbidities that are leading causes of death, and impact of guideline-recommended urticaria treatments on mortality rates.</p><p><strong>Methods: </strong>This was a retrospective population-based cohort study of electronic health records of 272,190 adult patients with CSU and 12,728,913 controls without urticaria from the US collaborative network TriNetX.</p><p><strong>Results: </strong>The study included 264,680 propensity score-matched patients with CSU (mean [SD] age = 47.5 [19.8] years; 71.5% female) and a corresponding number of controls without urticaria. Patients with CSU had higher 3-month (hazard ratio [HR] 2.10, 95% CI 1.97-2.22), 1-year (HR 1.77, 95% CI 1.71-1.83), and 5-year (HR 1.69, 95% CI 1.65-1.73) all-cause mortality (all P < .0001). Compared with controls, patients with CSU exhibited higher risk and rates of the leading causes of death in the United States, including suicidal ideations/suicide attempts (HR 3.14, 95% CI 3.00-3.28) and malignant neoplasms (HR 2.09, 95% CI 2.02-2.16). The risk of mortality appeared to be more pronounced in White and younger patients with CSU. All-cause mortality rates at 5 years were significantly lower in patients treated with second-generation H₁ antihistamines versus untreated patients (1.0% vs 2.3%; HR 1.84, P < .0001) and omalizumab-treated patients versus antihistamine-treated patients (0.7% vs 2.6%; HR 3.99, P = .0003).</p><p><strong>Conclusions: </strong>CSU is associated with increased mortality likely due to comorbidities, especially suicide, and effective CSU treatment may reduce mortality. These findings should be investigated in additional studies and in other populations.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828364","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}