Journal of Allergy and Clinical Immunology最新文献

英文中文

Opportunities for using artificial intelligence in air pollution and health research. 在空气污染与健康研究中使用人工智能的机遇。

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-10-03 DOI: 10.1016/j.jaci.2024.09.022

Roger D Peng, Sarah E Chambliss

引用次数: 0

Clinical effectiveness and safety of dupilumab in patients with chronic obstructive pulmonary disease: A 7-year population-based cohort study. 慢性阻塞性肺病患者使用杜匹单抗的临床有效性和安全性：一项为期 7 年的人群队列研究。

IF 3.5 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-10-03 DOI: 10.1016/j.jaci.2024.09.019

Chuan-Yen Sun, Yohannes Tesfaigzi, Gin-Yi Lee, Yi-Hsuan Chen, Scott T Weiss, Kevin Sheng-Kai Ma

Background: Previous randomized controlled trials have established the efficacy of dupilumab among patients with chronic obstructive pulmonary disease (COPD) treated with triple therapy over 52 weeks of follow-up.

Objective: This population-based cohort study aimed to explore the long-term safety and effectiveness of dupilumab in patients with COPD.

Methods: The study included US patients with COPD who were seen between April 2017 and August 2024. Patients initiating dupilumab and therapies that incorporated long-acting β₂-agonist (LABA) inhalers were included. Patients with asthma or lung cancer were excluded. The risk of outcomes occurring after initiation of dupilumab versus LABA-containing therapies was measured. For detailed methods, please see the Methods section in this article's Online Repository at www.jacionline.org.

Results: A total of 1521 dupilumab initiators and 1521 propensity score-matched patients who were receiving LABA-based therapies were included. Receiving dupilumab was associated with lower all-cause mortality (hazard ratio [HR] = 0.53, 95% CI = 0.43-0.65), fewer emergency department visits (HR = 0.78, 95% CI =0.69-0.89), and lower acute exacerbation rates (HR = 0.59, 95% CI = 0.53-0.65). Dupilumab was also associated with reductions in the requirement for short-acting β₂-agonists (HR = 0.48, 95% CI = 0.43-0.52) and short-acting muscarinic antagonists (HR = 0.43, 95% CI = 0.37-0.49) for symptom control. Additionally, dupilumab decreased rates of subsequent pneumonia (HR = 0.65, 95% CI = 0.50-0.86), and COPD-relevant comorbidities, including new-onset heart failure (HR = 0.69, 95% CI = 0.53-0.90) and new-onset anxiety (HR = 0.70, 95% CI =0.53-0.93).

Conclusions: In patients with COPD, dupilumab was associated with a lower mortality rate, fewer emergency department visits, and a reduced risk of acute exacerbations, respiratory symptoms, and respiratory infections. More studies are needed to validate the efficacy of dupilumab among patients with COPD of various severities.

背景：先前的随机对照试验证实了杜匹单抗对接受三联疗法治疗的慢性阻塞性肺病（COPD）患者的疗效：先前的随机对照试验证实，在接受三联疗法治疗的慢性阻塞性肺病（COPD）患者中，杜比单抗在52周的随访期间具有疗效：这项基于人群的队列研究旨在探讨杜比单抗对慢性阻塞性肺病患者的长期临床疗效：这项基于人群的队列研究纳入了2017年4月至2024年8月期间的美国COPD患者。研究纳入了开始使用杜必鲁单抗和长效β2-激动剂（LABA）吸入剂疗法的患者。哮喘或肺癌患者除外。对开始使用杜比单抗与含LABA疗法后的结果风险进行了测量。详细方法请参见本文在线资料库中的方法部分，网址：www.jacionline.org.Results：研究共纳入了1,521名开始使用杜匹鲁单抗的患者和1,521名接受LABA疗法的倾向评分匹配患者。接受杜匹单抗治疗的患者全因死亡率（HR:0.53，95% CI:0.43-0.65）、急诊就诊率（HR:0.78，95% CI:0.69-0.89）和急性加重（AE）率（HR:0.59，95% CI:0.53-0.65）均较低。杜匹鲁单抗还能减少控制症状所需的短效β2-激动剂（HR：0.48，95% CI：0.43-0.52）和短效毒蕈碱拮抗剂（HR：0.43，95% CI：0.37-0.49）。此外，杜匹鲁单抗还可减少继发肺炎（HR：0.65，95% CI：0.50-0.86）和慢性阻塞性肺疾病相关合并症，包括新发心衰（HR：0.69，95% CI：0.53-0.90）和新发焦虑（HR：0.70，95% CI：0.53-0.93）：结论：杜匹单抗可降低慢性阻塞性肺病患者的死亡率、急诊就诊率，降低AEs、呼吸道症状和呼吸道感染的风险。还需要更多的研究来验证杜匹单抗对不同严重程度的慢性阻塞性肺病患者的疗效。

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引用次数: 0

Role of anti-IgE in immediate drug allergy. 抗 IgE 在药物过敏中的作用

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-10-02 DOI: 10.1016/j.jaci.2024.09.021

Lily Li, Kimberly G Blumenthal

引用次数: 0

Phenotypic and pathomechanistic overlap between tapasin and TAP deficiencies tapasin 和 TAP 缺乏症在表型和病理机制上存在重叠。

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-10-01 DOI: 10.1016/j.jaci.2024.06.003

Background

Human tapasin deficiency is reported to cause an autosomal-recessive inborn error of immunity characterized by substantially reduced cell surface expression of major histocompatibility complex class I (MHC-I).

Objective

We evaluated the immunologic and clinical consequences of tapasin deficiency.

Methods

A novel homozygous variant in TAPBP was identified by means of whole genome sequencing. The expression of tapasin and both subunits of the transporter associated with antigen presentation (TAP) were evaluated by Western blot analysis. Cell surface and intracellular expression of MHC-I were evaluated by flow cytometry. Small interfering RNAs were used for silencing TAPBP expression in HEK293T cells.

Results

We identified a deletion in TAPBP (c.312del, p.(K104Nfs∗6)) causing tapasin deficiency in a patient with bronchiectasis and recurrent respiratory tract infections as well as herpes zoster. Besides substantial reduction in TAP1 and TAP2 expression, peripheral blood mononuclear cells from this patient and TAPBP-knockdown HEK293T cells, displayed reduced cell surface expression of MHC-I, while reduction in intracellular expression of MHC-I was less prominent, suggesting a defect in MHC-I trafficking to the plasma membrane. IFN-α improved cell surface expression of MHC-I in tapasin deficient lymphocytes and TAPBP-knockdown HEK293T cells, representing a possible therapeutic approach for tapasin deficiency.

Conclusion

Tapasin deficiency is a very rare inborn error of immunity, the pathomechanism and clinical spectrum of which overlaps with TAP deficiencies.

背景：据报道，人类绦虫素缺乏症会导致一种常染色体隐性先天性免疫错误（IEI），其特征是细胞表面主要组织相容性复合体I类（MHC-I）的表达量大幅减少：评估绦虫素缺乏症的免疫学和临床后果：方法：通过全基因组测序（WGS）确定了 TAPBP 的一个新型同源变体。方法：通过全基因组测序（WGS）确定了 TAPBP 的一个新型同源变异体，并用 Western 印迹法评估了 tapasin 和与抗原呈递相关的转运体（TAP）两个亚基的表达。流式细胞术评估了细胞表面和细胞内 MHC I 类的表达。小干扰 RNA（siRNA）用于沉默 HEK293T 细胞中 TAPBP 的表达：结果：我们在一名患有支气管扩张、反复呼吸道感染和带状疱疹的患者体内发现了 TAPBP 基因缺失（c.312del, p.(K104Nfs*6)），该基因缺失会导致 tapasin 缺乏症。除了 TAP1 和 TAP2 表达量大幅减少外，该患者的 PBMC 和 TAPBP 敲除的 HEK293T 细胞显示细胞表面的 MHC-I 表达量减少，而细胞内的 MHC-I 表达量减少不太明显，这表明 MHC-I 向质膜的转运存在缺陷。干扰素-α（IFN-α）改善了Tapasin缺乏症淋巴细胞和TAPBP敲除HEK293T细胞的MHC-I的细胞表面表达，是治疗Tapasin缺乏症的一种可能方法：结论：Tapasin 缺乏症是一种非常罕见的 IEI，其病理机制和临床范围与 TAP 缺乏症重叠。

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引用次数: 0

Nonsense CD247 mutations show dominant-negative features in T-cell receptor expression and function 有义 CD247 突变在 TCR 表达和功能方面表现出显性阴性特征。

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-10-01 DOI: 10.1016/j.jaci.2024.06.019

Background

The invariant TCR ζ/CD247 homodimer is crucial for TCR/CD3 expression and signaling through its 3 immunoreceptor tyrosine-based activation motifs (ITAMs). Homozygous null mutations in CD247 lead to immunodeficiency, while carriers exhibit 50% reduced surface CD3. It is unclear whether carriers of other CD247 variants show dominant-negative effects.

Objective

We sought to analyze and model the potential impact on T-cell receptor (TCR) expression and function of heterozygous nonsense CD247 mutations found in patients with signs of immunodeficiency or autoimmunity.

Methods

Jurkat T cells, either wild-type (WT) or CRISPR/Cas9-edited CD247-deficient (ZKO), were lentivirally transduced with WT CD247 or mutations ablating 1 (Q142X), 2 (Q101X), or 3 (Q70X) ITAMs.

Results

Three patients from unrelated families were studied. Two heterozygous nonsense CD247 mutations were identified (p.Y152X and p.Q101X), which affected ITAM-3 and ITAM-2 and ITAM-3, respectively. Both mutations were associated with low surface CD3 expression and normal intracellular CD247 levels using a transmembrane-specific antibody, but very low intracellular CD247 levels using an ITAM-3–specific one, suggesting the presence of truncated variants in T cells. Transduction of the mutations lacking 1, 2, or 3 ITAMs into ZKO cells could not restore normal surface CD3 expression (only 60%, 22%, and 10%, respectively), whereas in WT cells, normal surface CD3 expression was reduced (to 39%, 19%, and 9% of normal levels), and both effects were dependent on ITAM number. All 6 transfectants showed reduced CD69 induction (25% to 50%), indicating that they were unable to signal downstream properly, neither isolated nor associated with WT CD247.

Conclusions

Our results suggest that CD247 variants lacking ITAMs due to nonsense, but not null, mutations are defective for normal TCR assembly and exert a dominant-negative effect on TCR expression and signaling in vitro. This, in turn, may correlate with clinical features in vivo.

背景：不变TCRζ/CD247同源二聚体通过其三个基于免疫受体酪氨酸的激活基序（ITAM）对TCR/CD3的表达和信号转导至关重要。CD247 同源无效突变会导致免疫缺陷，而携带者的表面 CD3 会减少 50%。目前还不清楚其他 CD247 变异的携带者是否会出现显性阴性效应：目的：分析和模拟在有免疫缺陷或自身免疫迹象的患者中发现的杂合子无义 CD247 突变对 TCR 表达和功能的潜在影响：方法：用野生型 CD247 或消减一个（Q142X）、两个（Q101X）或三个（Q70X）ITAM 的突变慢病毒转染野生型（WT）或 CRISPR/Cas9 编辑的 CD247 缺失型（ZKO）的 Jurkat T 细胞：研究了来自非亲缘家庭的三名患者。研究发现了两个杂合子CD247无义突变（p.Y152X和p.Q101X），分别影响ITAM-3和ITAM-2+3。这两种突变都与低表面CD3表达、正常细胞内CD247水平（使用跨膜特异性抗体）以及极低细胞内CD247水平（使用ITAM-3特异性抗体）有关，这表明T细胞中存在截短变体。将缺少 1、2 或 3 个 ITAM 的突变体转入 ZKO 无法恢复正常的表面 CD3 表达（分别只有 60%、22% 和 10%），而转入 WT 则会降低其表达（分别降至正常水平的 39%、19% 和 9%），这两种效应都与 ITAM 数量有关。所有六种转染体都显示出 CD69 诱导减少（25%-50%），这表明它们既不能与野生型 CD247 分离，也不能与野生型 CD247 相关联，从而无法向下游适当地发出信号：我们的研究结果表明，由于无义突变（而非无效突变）而缺乏 ITAMs 的 CD247 变体在正常 TCR 组装方面存在缺陷，并在体外对 TCR 表达和信号转导产生显性负效应。这反过来又可能与体内的临床特征相关。

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引用次数: 0

Indoor air pollution and airway health 室内空气污染与呼吸道健康。

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-10-01 DOI: 10.1016/j.jaci.2024.08.013

Jared Radbel MD , Meghan E. Rebuli PhD , Howard Kipen MD, MPH , Emily Brigham MD, MHS

Because of the disproportionate amount of time that people spend indoors and the complexities of air pollutant exposures found there, indoor air pollution is a growing concern for airway health. Both infiltration of outdoor air pollution into the indoor space and indoor sources (such as smoke from tobacco products, cooking or heating practices and combustion of associated fuels, and household materials) contribute to unique exposure mixtures. Although there is substantial literature on the chemistry of indoor air pollution, research focused on health effects is only beginning to emerge and remains an important area of need to protect public health. We provide a review of emerging literature spanning the past 3 years and relating indoor air exposures to airway health, with a specific focus on the impact of either individual pollutant exposures or common combustion sources on the lower airways. Factors defining susceptibility and/or vulnerability are reviewed with consideration for priority populations and modifiable risk factors that may be targeted to advance health equity.

由于人们在室内度过的时间过长，以及室内空气污染物暴露的复杂性，室内空气污染日益受到人们对呼吸道健康的关注。室外空气污染渗入室内空间和室内污染源（如烟草产品产生的烟雾、烹饪或取暖方式以及相关燃料和家用材料的燃烧）都会造成独特的暴露混合物。虽然已有大量关于室内空气污染化学性质的文献，但以健康影响为重点的研究才刚刚开始，而且仍然是保护公众健康的一个重要需求领域。我们综述了过去三年新出现的有关室内空气暴露与气道健康的文献，重点关注个别污染物暴露或常见燃烧源对下呼吸道的影响。考虑到重点人群和可改变的风险因素，我们对确定易感性和/或脆弱性的因素进行了综述，以促进健康公平。

引用次数: 0

Obesity and Hormonal Influences on Asthma: Mechanisms, Management Challenges, and Emerging Therapeutic Strategies. 肥胖和荷尔蒙对哮喘的影响：机制、管理挑战和新兴治疗策略》。

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-10-01 DOI: 10.1016/j.jaci.2024.09.018

Natalia Weare-Regales, Tara Carr, Fernando Holguin, Christopher Andrew Tibbitt, Richard F Lockey

Obesity and hormonal dysregulation, common comorbidities of asthma, not only influence asthma risk and onset but can also complicate its management. The pathobiological characteristics of obesity, such as insulin resistance and metabolism alterations, can impact lung function and airway inflammation while highlighting potential opportunities for therapeutic intervention. Likewise, obesity alters immune cell phenotypes and corticosteroid pharmacokinetics. Hormones such as sex hormones, incretins, and thyroid hormones can also affect asthma. This review highlights the mechanisms underlying obesity-related asthma and hormonal pathologies while exploring potential therapeutic strategies and the need for more research and innovative approaches in managing these comorbid conditions.

肥胖和内分泌失调是哮喘的常见并发症，不仅会影响哮喘的风险和发病，还会使哮喘的治疗复杂化。肥胖的病理生物学特征，如胰岛素抵抗和新陈代谢改变，会影响肺功能和气道炎症，同时突出了潜在的治疗干预机会。同样，肥胖也会改变免疫细胞表型和皮质类固醇的药代动力学。性激素、增量激素和甲状腺激素等激素也会影响哮喘。这篇综述强调了与肥胖相关的哮喘和荷尔蒙病理机制，同时探讨了潜在的治疗策略，以及在管理这些合并症方面进行更多研究和采用创新方法的必要性。

引用次数: 0

Single cell RNA sequencing of human eosinophils from nasal polyps reveals eosinophil heterogeneity in chronic rhinosinusitis tissue 鼻息肉中人类嗜酸性粒细胞的单细胞 RNA 测序揭示了慢性鼻炎组织中嗜酸性粒细胞的异质性

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-10-01 DOI: 10.1016/j.jaci.2024.05.014

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 inflammation in the United States, but the actual roles that eosinophils play in CRSwNP remain largely unclear.

Objective

To reveal the roles and heterogeneity of eosinophils in nasal polyp (NP) tissue, we performed single cell RNA sequencing (scRNA-Seq) analysis of NP tissue.

Methods

Sinonasal tissues (NP and control sinus tissue) and patient matched peripheral blood (PB) samples were obtained from 5 control patients and 5 patients with CRSwNP. Eosinophils were enriched before processing for scRNA-Seq. The gene expression profiles in eosinophils were determined by microwell-based scRNA-Seq technology (BD Rhapsody platform). We predicted the overall function of NP eosinophils by Gene Ontology (geneontology.org) enrichment and pathway analyses and confirmed expression of selected genes by flow cytometry.

Results

After filtering out contaminating cells, we detected 5,542 eosinophils from control PB, 3,883 eosinophils from CRSwNP PB, 101 eosinophils from control sinus tissues (not included in further analyses), and 9,727 eosinophils from NPs by scRNA-Seq. We found that 204 genes were downregulated and 354 genes upregulated in NP eosinophils compared to all PB eosinophils (>1.5-fold, P_adj < .05). Upregulated genes in NP eosinophils were associated with activation, cytokine-mediated signaling, growth factor activity, NF-κB signaling, and antiapoptotic molecules. NP eosinophils displayed 4 clusters revealing potential heterogeneity of eosinophils in NP tissue.

Conclusions

Elevated eosinophils in NP tissue appear to exist in several subtypes that may play important pathogenic roles in CRSwNP, in part by controlling inflammation and hyperproliferation of other cells.

背景在美国，伴有鼻息肉的慢性鼻窦炎（CRSwNP）以2型炎症为特征，但嗜酸性粒细胞在CRSwNP中的实际作用在很大程度上仍不清楚。为了揭示嗜酸性粒细胞在鼻息肉（NP）组织中的作用和异质性，我们对 NP 组织进行了单细胞 RNA 测序（scRNA-Seq）分析。在进行 scRNA-Seq 处理之前，对嗜酸性粒细胞进行了富集。通过微孔 scRNA-Seq 技术（BD Rhapsody 平台）测定了嗜酸性粒细胞的基因表达谱。我们通过基因本体论（geneontology.org）富集和通路分析预测了 NP 嗜酸性粒细胞的整体功能，并通过流式细胞仪确认了所选基因的表达。结果在过滤掉污染细胞后，我们通过 scRNA-Seq 检测到了来自对照 PB 的 5542 个嗜酸性粒细胞、来自 CRSwNP PB 的 3883 个嗜酸性粒细胞、来自对照鼻窦组织的 101 个嗜酸性粒细胞（未纳入进一步分析）以及来自 NPs 的 9727 个嗜酸性粒细胞。我们发现，与所有 PB 嗜酸性粒细胞相比，NP 嗜酸性粒细胞中有 204 个基因下调，354 个基因上调（>1.5 倍，Padj <.05）。NP嗜酸性粒细胞中上调的基因与活化、细胞因子介导的信号转导、生长因子活性、NF-κB信号转导和抗凋亡分子有关。NP嗜酸性粒细胞显示出4个集群，揭示了NP组织中嗜酸性粒细胞的潜在异质性。结论NP组织中升高的嗜酸性粒细胞似乎存在多种亚型，它们可能在CRSwNP中发挥重要的致病作用，部分原因是它们控制了炎症和其他细胞的过度增殖。

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引用次数: 0

News beyond our pages - October 2024 本版以外的新闻 - 2024 年 10 月

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-10-01 DOI: 10.1016/j.jaci.2024.08.007

引用次数: 0

Indoor air: Guidelines, policies, and regulation 室内空气：准则、政策和法规。

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-10-01 DOI: 10.1016/j.jaci.2024.06.015

引用次数: 0

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