Journal of Allergy and Clinical Immunology最新文献

{"title":"Update on type 2 immunity.","authors":"Magdalena M Gorska","doi":"10.1016/j.jaci.2024.11.003","DOIUrl":"10.1016/j.jaci.2024.11.003","url":null,"abstract":"<p><p>This review article summarizes and comments on the mechanistic work on type 2 immunity published between January 2022 and September 2024. Type 2 immunity is characterized by the production of IL-4, IL-5, IL-9, and IL-13 and is primarily known for its detrimental roles in allergic diseases and its protective roles in helminth infections. Other functions of type 2 immunity include protection against venoms and toxins, wound healing, tissue remodeling, regeneration, and metabolic homeostasis. This review article discusses novel findings on regulation of these processes and disease states by select cells and humoral factors of type 2 immunity, including group 2 innate lymphoid cells, CD4 T cells, mast cells, peripheral neurons, and IgE. The article also describes novel discoveries on regulation of these factors and cells by environmental exposures and the host. Further, the article discusses select genetic mouse models that were developed recently and have the potential to accelerate the field. Finally, the article comments on the significance of novel discoveries to clinical medicine, including drug development.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621014","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":"Phase 2b randomized clinical trial of amlitelimab, an anti-OX40 ligand antibody, in patients with moderate-to-severe atopic dermatitis.","authors":"Stephan Weidinger, Andrew Blauvelt, Kim A Papp, Adam Reich, Chih-Hung Lee, Margitta Worm, Charles Lynde, Yoko Kataoka, Peter Foley, Xiaodan Wei, Wanling Wong, Anne-Catherine Solente, Christine Weber, Samuel Adelman, Sonya Davey, Fabrice Hurbin, Natalie Rynkiewicz, Karl Yen, John T O'Malley, Charlotte Bernigaud","doi":"10.1016/j.jaci.2024.10.031","DOIUrl":"10.1016/j.jaci.2024.10.031","url":null,"abstract":"<p><strong>Background: </strong>Amlitelimab, a fully human nondepleting mAb targeting OX40 ligand on antigen-presenting cells, could prevent T-cell-driven inflammation seen in atopic dermatitis (AD).</p><p><strong>Objective: </strong>This trial evaluated the efficacy and safety of amlitelimab in adults with AD.</p><p><strong>Methods: </strong>In this 2-part, phase 2b, randomized, double-blinded placebo-controlled trial (ClinicalTrials.gov identifier NCT05131477), patients received subcutaneous amlitelimab every 4 weeks at doses of 250 mg plus a 500-mg loading dose, 250 mg, 125 mg, or 62.5 mg or placebo for 24 weeks in Part 1 (1:1:1:1:1 randomization). In Part 2, clinical responders were reallocated 3:1 to stop taking amlitelimab or continue the previous dose regimen for 28 weeks. The primary end point was percentage of change in Eczema Area and Severity Index (EASI) from baseline to week 16.</p><p><strong>Results: </strong>In all, 390 and 190 patients enrolled in Part 1 and Part 2, respectively. A significant percentage of change decrease in EASI was observed with amlitelimab doses versus with placebo (P < .001). Clinical responses at week 24 (Investigator Global Assessment 0/1 and/or a 75% reduction in EASI) were maintained at week 52 in patients continuing or stopping amlitelimab. Of the patients maintaining clinical response at week 52 after no longer receiving treatment, more than 80% had serum amlitelimab concentrations less than the 4-μg/mL threshold for several weeks before week 52. Reductions in AD-related biomarkers during Part 1 were maintained through Part 2. Amlitelimab was well tolerated over 52 weeks.</p><p><strong>Conclusions: </strong>Amlitelimab treatment significantly reduced clinical and biomarker responses, and was well tolerated in adults with AD through week 52. Sustained responses were observed in the majority of patients for 28 weeks after they had stopped taking amlitelimab.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620988","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":"Prevalence and outcomes of cancer and treatment-associated toxicities for patients with ataxia telangiectasia.","authors":"Aimee Magnarelli, Qi Liu, Fan Wang, Xiao P Peng, Jennifer Wright, Ninad Oak, Valerie Natale, Cynthia Rothblum-Oviatt, Maureen A Lefton-Greif, Sharon McGrath-Morrow, Thomas O Crawford, Matthew J Ehrhardt, Howard M Lederman, Richa Sharma","doi":"10.1016/j.jaci.2024.10.023","DOIUrl":"10.1016/j.jaci.2024.10.023","url":null,"abstract":"<p><strong>Background: </strong>Ataxia telangiectasia (A-T) is a DNA repair disorder with cancer predisposition.</p><p><strong>Objective: </strong>We sought to characterize the prevalence and outcomes of hematologic and solid cancers and treatment-associated toxicities in individuals with A-T.</p><p><strong>Methods: </strong>Data were retrospectively analyzed from the Johns Hopkins Ataxia Telangiectasia Clinical Center cohort. Cumulative incidence and standardized incidence ratios of cancer, survival probability after cancer diagnosis, and standardized mortality ratios were calculated. Cox regression estimated risk of death on the basis of chemotherapy (standard vs reduced) dosing, and multivariable logistic regression evaluated cancer risk associations with ataxia telangiectasia mutated (ATM) exons and variants.</p><p><strong>Results: </strong>Eighty-four (16.5%) of 508 individuals were diagnosed with a primary cancer, of whom 62 (74%) were hematologic in origin and 22 (26%) were solid-organ cancers. The cumulative incidence of cancer was 29% by age 35 years. Non-Hodgkin lymphoma occurred most frequently (n = 39), whereas solid cancers disproportionately affected those 18 years and older (n = 22). The standardized mortality ratio was 24.6 (95% CI, 21.1-28.4) overall and 232.9 (95% CI,178.1-299.2) among individuals with cancer. Risk of death was higher when treated with standard/unknown versus modified chemotherapy (hazard ratio, 2.2; 95% CI, 1.1-4.4; P = .024). Chemotherapy-associated toxicities developed in 58% of individuals, predominantly neurologic (n = 14) and gastrointestinal (n = 10) systems. Three exons were enriched for cancer-associated variants.</p><p><strong>Conclusions: </strong>Individuals with A-T experience a wide array of blood and solid-organ malignancies, high mortality rates, and treatment-related toxicities, highlighting need for targeted therapies to mitigate toxicity and optimize survival.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620990","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":"Reply.","authors":"Pedro A Lamothe, Martin C Runnstrom, F Eun-Hyung Lee","doi":"10.1016/j.jaci.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.003","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620998","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":"Profiling immune cell tissue niches in the spatial -omics era.","authors":"Colin Y C Lee, James McCaffrey, Dominic McGovern, Menna R Clatworthy","doi":"10.1016/j.jaci.2024.11.001","DOIUrl":"10.1016/j.jaci.2024.11.001","url":null,"abstract":"<p><p>Immune responses require complex, spatially coordinated interactions between immune cells and their tissue environment. For decades, we have imaged tissue sections to visualize a limited number of immune-related macromolecules in situ, functioning as surrogates for cell types or processes of interest. However, this inevitably provides a limited snapshot of the tissue's immune landscape. Recent developments in high-throughput spatial -omics technologies, particularly spatial transcriptomics, and its application to human samples has facilitated a more comprehensive understanding of tissue immunity by mapping fine-grained immune cell states to their precise tissue location while providing contextual information about their immediate cellular and tissue environment. These data provide opportunities to investigate mechanisms underlying the spatial distribution of immune cells and its functional implications, including the identification of immune niches, although the criteria used to define this term have been inconsistent. Here, we review recent technological and analytic advances in multiparameter spatial profiling, focusing on how these methods have generated new insights in translational immunology. We propose a 3-step framework for the definition and characterization of immune niches, which is powerfully facilitated by new spatial profiling methodologies. Finally, we summarize current approaches to analyze adaptive immune repertoires and lymphocyte clonal expansion in a spatially resolved manner.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620992","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":"Impact of biologics on the immune response to mRNA COVID-19 vaccination in patients with asthma.","authors":"Shu-Yi Liao, Barry Make, Michael E Wechsler","doi":"10.1016/j.jaci.2024.09.028","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.09.028","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620974","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":"Booster vaccination normalizes postvaccination immunity in patients with severe asthma.","authors":"Hitasha Rupani, Rekha Chaudhuri, David J Jackson, Helen Moyses, Ramesh J Kurukulaaratchy, Hans Michael Haitchi, Michael R Edwards, Sebastian L Johnston, Ratko Djukanovic","doi":"10.1016/j.jaci.2024.09.027","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.09.027","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620967","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":"Implementation of the esophageal string test in clinical practice and research.","authors":"Shauna Schroeder, Cindy S Bauer, Benjamin L Wright","doi":"10.1016/j.jaci.2024.11.002","DOIUrl":"10.1016/j.jaci.2024.11.002","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620976","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":"Effect of mepolizumab in airway remodeling in patients with late-onset severe asthma with an eosinophilic phenotype.","authors":"Kalliopi Domvri, Ioanna Tsiouprou, Petros Bakakos, Paschalis Steiropoulos, Konstantinos Katsoulis, Konstantinos Kostikas, Katerina M Antoniou, Andriana I Papaioannou, Nikoletta Rovina, Paraskevi Katsaounou, Theodora Papamitsou, Nicoleta Pastelli, Stavros Tryfon, Evangelia Fouka, Despoina Papakosta, Stelios Loukides, Konstantinos Porpodis","doi":"10.1016/j.jaci.2024.10.024","DOIUrl":"10.1016/j.jaci.2024.10.024","url":null,"abstract":"<p><strong>Background: </strong>Clinical trials and real-world experience have provided evidence for the clinical benefits of mepolizumab, an anti-IL-5 biologic, in severe asthma. However, limited data exist regarding the impact of mepolizumab on airway remodeling.</p><p><strong>Objective: </strong>We sought to investigate the effect of mepolizumab on airway structural remodeling in patients treated for severe asthma in routine clinical care.</p><p><strong>Methods: </strong>The MESILICO (Efficacy of Mepolizumab in patients with latE-onset Severe eosInophiLic asthma and fIxed obstruCtiOn) study is a multicenter study involving 8 pulmonology departments in Greece. This study focused on patients who initiated mepolizumab for severe asthma with an eosinophilic phenotype and had late-onset disease with obstructive patterns (impaired reversibility). Forty-seven patients were recruited, of whom 41 were enrolled in the bronchoscopy substudy. The findings were related to clinical outcome.</p><p><strong>Results: </strong>After 12 months, mepolizumab treatment was associated with significant improvements in lung function and Asthma Control Test score, along with a significant decrease in severe exacerbation events (P < .001). Thirty-four of the 41 participants (83%) had paired biopsies for comparative analysis. There was a significant reduction from baseline in sub-basement membrane thickness, airway smooth muscle area, airway smooth muscle layer thickness, extent of epithelial damage, and number of tissue eosinophils (all P < .001). The extent of reduction in airway smooth muscle layer thickness positively correlated with the submucosal eosinophil reduction (r = 0.599; P < .001).</p><p><strong>Conclusions: </strong>This study identified that 12 months of mepolizumab treatment in patients with late-onset severe asthma, who are also characterized by eosinophilic and impaired reversibility phenotypes, not only leads to clinical improvement but also reduces indices of airway tissue remodeling suggestive of a disease-modifying effect.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620970","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":"Reply.","authors":"Benjamin L Wright, Jonathan M Spergel, Emily C McGowan","doi":"10.1016/j.jaci.2024.09.026","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.09.026","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620994","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}