Journal of Allergy and Clinical Immunology最新文献

英文中文

Multiomics insights into retinoic acid–mediated regulation of eosinophils in severe asthma 重度哮喘患者视黄酸介导嗜酸性粒细胞调节的多组学研究

IF 11.2 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2026-02-01 DOI: 10.1016/j.jaci.2025.10.029

Jun Miyata MD, PhD , Keeya Sunata MD, PhD , Hisashi Sasaki MD , Yusuke Kawashima PhD , Yo Otsu MD , Ryuta Onozato MD , Emiko Matsuyama MD , Shinichi Okuzumi MD, PhD , Takao Mochimaru MD, PhD , Katsunori Masaki MD, PhD , Hiroki Kabata MD, PhD , Ryo Konno PhD , Masaki Ishikawa PhD , Yoshinori Hasegawa PhD , Yoshifumi Kimizuka MD, PhD , Makoto Arita PhD , Koichi Fukunaga MD, PhD

Background

Severe asthma is marked by persistent eosinophilic inflammation, but the role of all-trans retinoic acid (ATRA) in eosinophil homeostasis remains unclear.

Objective

This study examined the regulatory role of ATRA in eosinophil function in severe asthma.

Methods

Multiomics analysis (transcriptomics, proteomics, and lipidomics) was conducted on blood eosinophils from healthy participants and patients with severe asthma. The effects of ATRA on eosinophil function were further analyzed by using flow cytometry and quantitative RT-PCR.

Results

Transcriptomic profiling of eosinophils from patients with severe asthma revealed a distinct gene expression signature, with upregulation of the genes GGT5, IL2RA, CCL23, and NOD2 and downregulation of SPRY2 and HIC1. This phenotype was driven by type 2 cytokines (IL-5 and IL-4) and muramyl dipeptide but was counterregulated by ATRA. Proteomic analysis showed increased expression of P-selectin glycoprotein ligand-1 in SA-EOS, which was upregulated by type 2 cytokines and downregulated by ATRA. Lipidomic analysis identified dysregulated 15-lipoxygenase metabolism in SA-EOS, with ATRA selectively inhibiting cysteinyl leukotriene metabolism while sparing the 15-lipoxygenase pathway. Multiomics analysis of eosinophils from ATRA-treated healthy participants revealed specific downregulation of IL1RL1 and IL3RA, reducing responsiveness to IL-33 and IL-3 and distinguishing them from IL-5–induced eosinophils.

Conclusion

These findings highlight the role of ATRA in maintaining eosinophil homeostasis and counterregulating IL-5–driven activation, thus offering insights into potential therapeutic strategies for severe asthma.

重度哮喘以持续的嗜酸性粒细胞炎症为特征，但全反式维甲酸（ATRA）在嗜酸性粒细胞稳态中的作用尚不清楚。目的探讨ATRA对重度哮喘患者嗜酸性粒细胞功能的调节作用。方法采用多组学（转录组学、蛋白质组学和脂质组学）对健康受试者和重度哮喘患者的血嗜酸性粒细胞进行分析。采用流式细胞术和定量RT-PCR分析ATRA对嗜酸性粒细胞功能的影响。结果重度哮喘患者嗜酸性粒细胞的转录组学分析显示，GGT5、IL2RA、CCL23和NOD2基因表达上调，SPRY2和HIC1基因表达下调，具有明显的基因表达特征。这种表型由2型细胞因子（IL-5和IL-4）和muramyl二肽驱动，但被ATRA拮抗。蛋白质组学分析显示，SA-EOS中p -选择素糖蛋白配体1的表达增加，2型细胞因子上调p -选择素糖蛋白配体1，ATRA下调p -选择素糖蛋白配体1的表达。脂质组学分析发现SA-EOS中15-脂氧合酶代谢失调，ATRA选择性抑制半胱氨酸白三烯代谢，同时保留15-脂氧合酶途径。对atra治疗的健康参与者的嗜酸性粒细胞的多组学分析显示，IL1RL1和IL3RA特异性下调，降低了对IL-33和IL-3的反应性，并将它们与il -5诱导的嗜酸性粒细胞区分出来。结论ATRA在维持嗜酸性粒细胞稳态和抑制il -5激活中的作用，为重症哮喘的潜在治疗策略提供了新的思路。

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引用次数: 0

Evaluating Diet and Nutrition-Related Concerns in a Multidisciplinary Clinic for Pediatric Patients with Atopic Dermatitis 评估儿童特应性皮炎患者的多学科临床饮食和营养相关问题

IF 11.2 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2026-02-01 DOI: 10.1016/j.jaci.2025.12.025

Wendy Elverson RD LDN , Tina Ho MD , Karol Timmons RN MS CPNP , Maya Dayanim , Lynda Schneider MD FAAAAI , Jennifer Lebovidge PhD

引用次数: 0

Meeting Announcement 会议公告

IF 11.2 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2026-02-01 DOI: 10.1016/S0091-6749(25)02241-9

引用次数: 0

Quantitative Systems Biology Modeling Estimates Extent of Excessive Kallikrein Generation in Hereditary Angioedema Patients 定量系统生物学模型估计遗传性血管性水肿患者钾激肽过量产生的程度

IF 11.2 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2026-02-01 DOI: 10.1016/j.jaci.2025.12.009

Allen Kaplan MD FAAAAI , Catherine Miller PharmD, MPH , Mrinal Shah PhD , David Maag PhD , James Butler , Jonathan Phillips

引用次数: 0

Response Drivers in Sebetralstat Placebo-controlled Clinical Trials Sebetralstat安慰剂对照临床试验中的反应驱动因素

IF 11.2 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2026-02-01 DOI: 10.1016/j.jaci.2025.12.016

Jonathan Bernstein MD FAAAAI , Emel Aygören-Pürsün MD , Danny Cohn MD PhD , Henriette Farkas MD PhD DSc , William Lumry MD FAAAAI , Andrea Zanichelli MD , James Hao PhD , Michael Smith PharmD , Paul Audhya MD , Erik Hansen , Nathan Teuscher , Marc Riedl MD MS

引用次数: 0

Minimally invasive skin tape strip proteomic analysis demonstrates significant inhibition of epidermal hyperplasia protein cluster in pediatric atopic dermatitis patients treated with dupilumab 微创皮肤胶带条带蛋白质组学分析显示，在接受dupilumab治疗的儿童特应性皮炎患者中，表皮增生蛋白簇有显著的抑制作用

IF 11.2 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2026-02-01 DOI: 10.1016/j.jaci.2025.12.059

Elena Goleva PhD , Evgeny Berdyshev PhD , Simion Kreimer PhD , Taras Lyubchenko , Emilie Gloaguen , Inoncent Agueusop , Peck Ong MD FAAAAI , Simon Danby , Michael Cork BSc MB PhD FRCP , Joseph Zahn MD , Annie Zhang MD , Donald Leung MD PhD FAAAAI

引用次数: 0

Concurrent Improvement Over Time in Multiple Aspects of Quality of Life in Patients with Chronic Spontaneous Urticaria Treated with Omalizumab 慢性自发性荨麻疹患者接受Omalizumab治疗后，生活质量的多个方面随着时间的推移同步改善

IF 11.2 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2026-02-01 DOI: 10.1016/j.jaci.2025.12.041

Giselle Mosnaim , Sarbjit Saini MD FAAAAI , Michael Holden MD, MS , Ben Trzaskoma , Jonathan Bernstein MD FAAAAI

引用次数: 0

Late effects after hematopoietic stem cell transplantation in patients with HLH: A Histiocyte Society, PDWP, IEWP, and TCWP EBMT Study 造血干细胞移植对HLH患者的晚期影响：组织细胞学会、PDWP、IEWP和TCWP EBMT研究

IF 11.2 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2026-02-01 DOI: 10.1016/j.jaci.2025.09.014

Kim Ramme MD, PhD , AnnaCarin Horne MD, PhD , Karin Beutel MD , Jacques-Emmanuel Galimard PhD , Ali Abdallah Alahmari MD , Giorgio Ottaviano MD , Despina Moshous MD, PhD , Savas Kansoy MD , Zohreh Nademi MD, PhD , Maura Faraci MD , Mikael Sundin MD, PhD , Franca Fagioli MD , Michael H. Albert MD , Petr Sedlacek MD , Yves Bertrand MD, PhD , Franco Locatelli MD, PhD , Catherine Paillard MD , Karin Mellgren MD, PhD , Ingo Müller MD , Johann Greil MD , Selim Corbacioglu MD, PhD

Background

Hematopoietic stem cell transplantation (HCT) is the only curative treatment in primary hemophagocytic lymphohistiocytosis (pHLH). However, HCT is associated with a wide range of late effects (LEs).

Objective

We sought to characterize the long-term outcome and LEs following HCT in pHLH.

Methods

A total of 274 children with pHLH from the European Society for Blood and Marrow Transplantation registry who underwent allogeneic HCT between 2004 and 2015 were included. Multivariable logistic regression models were used to evaluate the adjusted impact of baseline variables on central nervous system and hormonal LEs, respectively.

Results

A broad spectrum of LEs was identified, with neurologic (31%) and hormonal (34.8%) complications being the most prevalent. Chemotherapy (HLH-1994/HLH-2004) before HCT was identified as a significant risk factor for endocrinological LEs (P = .03), highlighting a novel aspect not previously reported. The presence of neurologic abnormality at diagnosis was an independent risk factor for neurologic LEs (P < .001) as was incomplete remission status at the time of HCT (P = .04).

Conclusions

HCT has significantly improved survival in patients with pHLH. However, survivors still face significant risks of LEs.

背景：造血干细胞移植是治疗原发性噬血细胞淋巴组织细胞病的唯一有效方法。然而，造血干细胞移植具有广泛的晚期效应。目的探讨造血干细胞移植治疗原发性噬血细胞淋巴组织细胞病的远期疗效和后期效应。方法纳入2004年至2015年间接受同种异体造血干细胞移植的EBMT登记的274例pHLH患儿。采用多变量logistic回归模型分别评估基线变量对中枢神经系统和激素晚期效应的调整影响。结果发现了广谱的晚期效应，其中神经系统并发症（31%）和激素并发症（34.8%）最为普遍。造血干细胞移植前化疗（HLH-94/HLH04）被确定为内分泌晚期效应的重要危险因素（p=0.03），突出了一个以前未报道的新方面。诊断时神经系统异常的存在是神经系统晚期效应的独立危险因素（p<0.001）， HCT时不完全缓解状态也是（p=0.04）。结论造血干细胞移植可显著提高原发性噬血细胞淋巴组织细胞增多症患者的生存，但存活者仍面临显著的后期效应风险。

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引用次数: 0

COVID-19 infection raises respiratory type 2 inflammatory disease risk, whereas vaccination is protective COVID-19感染增加了呼吸道2型炎症性疾病的风险，而疫苗接种具有保护作用。

IF 11.2 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2026-02-01 DOI: 10.1016/j.jaci.2025.07.030

Henning Olbrich MD , Sophie L. Preuß MD , Khalaf Kridin MD, PhD , Gema Hernandez PhD , Diamant Thaçi MD , Ralf J. Ludwig MD , Philip Curman MD, PhD

Background

Coronavirus disease 2019 (COVID-19) infection and vaccination have unclear impacts on type 2 inflammatory diseases. Although viral infections can drive immune dysregulation, the extent to which COVID-19 infection and vaccination affect type 2 inflammatory diseases in various organ systems remains underexplored.

Objective

We sought to assess the risk of new-onset type 2 inflammatory diseases after COVID-19 infection and vaccination.

Methods

We conducted a large-scale retrospective matched cohort study using a US electronic health records database of more than 118 million patients. Three cohorts were defined: individuals with COVID-19 infection (n = 973,794), individuals with COVID-19 vaccination (n = 691,270), and unexposed controls (n = 4,388,409). Propensity score matching balanced demographic and clinical covariates. We calculated hazard ratios (HRs) for incident asthma, allergic rhinitis, chronic rhinosinusitis, atopic dermatitis, and eosinophilic esophagitis over 3-month follow-up.

Results

COVID-19 infection significantly increased the risks of asthma (HR 1.656, 95% CI 1.590-1.725), allergic rhinitis (HR 1.272, 95% CI 1.214-1.333), and chronic rhinosinusitis (HR 1.744, 95% CI 1.671-1.821). Risks for atopic dermatitis or eosinophilic esophagitis remained unchanged. In contrast, vaccination lowered the risks of asthma (HR 0.678, 95% CI 0.636-0.722) and chronic rhinosinusitis (HR 0.799, 95% CI 0.752-0.850). Direct comparison showed a 2- to 3-fold greater risk of respiratory type 2 inflammatory diseases with infection than with vaccination.

Conclusions

COVID-19 infection is associated with a heightened risk of respiratory type 2 inflammatory diseases, whereas vaccination appears protective.

背景covid -19感染和疫苗接种对2型炎症性疾病的影响尚不清楚。尽管病毒感染可导致免疫失调，但COVID-19感染和疫苗接种在多大程度上影响各器官系统的2型炎症性疾病仍未得到充分探讨。目的评估COVID-19感染和疫苗接种后新发2型炎症性疾病的风险。方法：我们在美国电子健康记录数据库中对超过1.18亿患者进行了大规模回顾性匹配队列研究。定义了三个队列：COVID-19感染个体（973,794），COVID-19疫苗接种个体（691,270）和未暴露对照组（4,388,409）。倾向得分匹配平衡人口统计学和临床协变量。我们计算了三个月随访期间哮喘、变应性鼻炎、慢性鼻窦炎、特应性皮炎和嗜酸性粒细胞性食管炎发生的风险比。结果scovid -19感染显著增加哮喘（风险比1.656,95%可信区间1.590 ~ 1.725）、变应性鼻炎（风险比1.272，风险比1.214 ~ 1.333）、慢性鼻窦炎（风险比1.744，风险比1.671 ~ 1.821）的发病风险。特应性皮炎或嗜酸性食管炎的风险保持不变。相比之下，接种疫苗降低了哮喘（0.678,0.636-0.722）和慢性鼻窦炎（0.799,0.752-0.850）的风险。直接比较表明，与接种疫苗相比，感染呼吸道2型炎症性疾病的风险高出两到三倍。结论covid -19感染与呼吸道2型炎症性疾病的风险增加有关，而接种疫苗具有保护作用。临床意义covid -19疫苗接种可减少由2型炎症引起的呼吸道并发症，从而减轻疾病负担。

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引用次数: 0

Post–COVID-19 atopic diseases risk: The need to disentangle variant-specific effects covid -19后的特应性疾病风险：需要理清变异特异性效应。

IF 11.2 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2026-02-01 DOI: 10.1016/j.jaci.2025.10.015

Mário Morais-Almeida MD , Bernardo Sousa-Pinto MD, PhD , Raquel Baptista-Pestana MD , Jean Bousquet MD, PhD

引用次数: 0

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Journal of Allergy and Clinical Immunology

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