Allergology International最新文献_第3页

Aspergillus fumigatus extract modulates human eosinophils via NOD2 and oxidative stress 曲霉菌提取物通过 NOD2 和氧化应激调节人类嗜酸性粒细胞

IF 6.2 2区医学 Q1 ALLERGY

Allergology International

Pub Date : 2025-01-01 DOI: 10.1016/j.alit.2024.08.009

Hisashi Sasaki , Jun Miyata , Yusuke Kawashima , Ryo Konno , Masaki Ishikawa , Yoshinori Hasegawa , Ryuta Onozato , Yo Otsu , Emiko Matsuyama , Keeya Sunata , Katsunori Masaki , Hiroki Kabata , Yoshifumi Kimizuka , Tomoe Abe , Shigeharu Ueki , Koichiro Asano , Akihiko Kawana , Koichi Fukunaga

Background

Aspergillus fumigatus is a pathogenic fungus known to be associated with severe asthma and allergic bronchopulmonary mycosis. However, the precise mechanisms underlying airway inflammation remain unclear. In this study, we investigated the direct modulation of human eosinophils by A. fumigatus and identified the specific mechanism of airway inflammation.

Methods

Eosinophils isolated from healthy subjects were stimulated with extracts of A. fumigatus. Multi-omics analysis, comprising transcriptomic and proteomic analyses, was performed. The expression of specific factors was evaluated using quantitative real-time polymerase chain reaction and flow cytometry. Mechanistic analyses were performed using NOD2 inhibitor and N-acetyl-l-cysteine (NAC).

Results

The A. fumigatus extract changed the expression of adhesion molecules (CD62L and CD11b) and CD69 on the surface of eosinophils, without affecting their viability, via nucleotide-binding oligomerization domain-containing protein 2 (NOD2) but not protease activity. Investigation using kinase inhibitors showed that A. fumigatus extract-induced modulation was partly mediated via p38 mitogen-activated protein kinases. Multi-omics analysis revealed that A. fumigatus-induced gene and protein expression profiles were characterized by the upregulation of oxidative stress-related molecules, including heat shock proteins (HSP90AA1, HSP90AB1, SRXN1, and HMOX1). NOD2 inhibitor and NAC differentially inhibited A. fumigatus-induced inflammatory changes. Additional multi-omics analysis identified that NOD2 signaling induced gene signatures different from those of interleukin (IL)-5 and elicited synergistic change with IL-5.

Conclusions

A. fumigatus modulates human eosinophils via NOD2 and oxidative stress-mediated signaling. NOD2 signaling potentiated IL-5-induced activation, suggesting its pathogenic role in type 2 inflammation. NOD2 inhibitors and antioxidants can have therapeutic potential against A. fumigatus-related allergic disorders.

背景：曲霉菌是一种致病真菌，已知与严重哮喘和过敏性支气管肺霉菌病有关。然而，气道炎症的确切机制仍不清楚。在这项研究中，我们研究了烟曲霉对人类嗜酸性粒细胞的直接调节，并确定了气道炎症的具体机制：方法：用烟曲霉提取物刺激从健康人体内分离的嗜酸性粒细胞。方法：用烟曲霉菌提取物刺激从健康受试者体内分离出的嗜酸性粒细胞，进行多组学分析，包括转录组和蛋白质组分析。使用定量实时聚合酶链反应和流式细胞术评估了特定因子的表达。使用 NOD2 抑制剂和 N-乙酰-L-半胱氨酸（NAC）进行了机理分析：结果：烟曲霉菌提取物通过核苷酸结合寡聚化结构域含蛋白 2（NOD2）而非蛋白酶活性改变了嗜酸性粒细胞表面粘附分子（CD62L 和 CD11b）和 CD69 的表达，但不影响其活力。使用激酶抑制剂进行的研究表明，烟曲霉提取物诱导的调节作用部分是通过 p38 丝裂原活化蛋白激酶介导的。多组学分析表明，烟曲霉诱导的基因和蛋白质表达谱的特点是氧化应激相关分子的上调，包括热休克蛋白（HSP90AA1、HSP90AB1、SRXN1 和 HMOX1）。NOD2 抑制剂和 NAC 对烟曲霉菌诱导的炎症变化有不同程度的抑制作用。额外的多组学分析发现，NOD2 信号诱导的基因特征与白细胞介素（IL）-5 的基因特征不同，并与 IL-5 产生协同变化：结论：烟曲霉通过NOD2和氧化应激介导的信号转导调节人类嗜酸性粒细胞。结论：嗜酸性粒细胞酵母菌通过 NOD2 和氧化应激介导的信号调节人嗜酸性粒细胞，NOD2 信号增强了 IL-5 诱导的活化，表明其在 2 型炎症中的致病作用。NOD2抑制剂和抗氧化剂具有治疗烟曲霉相关过敏性疾病的潜力。

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引用次数: 0

Follicular T cells and the control of IgE responses 滤泡 T 细胞与 IgE 反应的控制。

IF 6.2 2区医学 Q1 ALLERGY

Allergology International

Pub Date : 2025-01-01 DOI: 10.1016/j.alit.2024.09.007

Pablo F. Cañete , Di Yu

Atopy is considered the epidemic of the 21st century, and while decades of research have established a direct link between Th2 cells driving pathogenic IgE-mediated allergic disease, only in the past years have T follicular helper (Tfh) cells emerged as pivotal drivers of these responses. In this review, we will examine the molecular mechanisms governing the IgE response, with a particular emphasis on the key cytokines and signaling pathways. We will discuss the exclusion of IgE-producing B cells from germinal centers and explore the recently established role of follicular T cell function and heterogeneity in driving or curtailing these immune responses. Additionally, we will assess the current state of major monoclonal antibodies and allergen immunotherapies designed to counteract Th2-driven inflammation, as well as reflect on the need to investigate how these biologics impact Tfh cell activity, differentiation, and function, as these insights could pave the way for much-needed therapeutic innovation in the treatment of allergic diseases.

过敏症被认为是 21 世纪的流行病，尽管数十年的研究已经证实 Th2 细胞与 IgE 介导的致病性过敏性疾病之间存在直接联系，但直到最近几年，T 滤泡辅助细胞（Tfh）才成为这些反应的关键驱动因素。在这篇综述中，我们将研究支配 IgE 反应的分子机制，特别强调关键细胞因子和信号通路。我们将讨论生殖中心对产生 IgE 的 B 细胞的排斥，并探讨最近确立的滤泡 T 细胞功能和异质性在驱动或抑制这些免疫反应中的作用。此外，我们还将评估旨在对抗 Th2 驱动的炎症的主要单克隆抗体和过敏原免疫疗法的现状，并思考研究这些生物制剂如何影响 Tfh 细胞的活性、分化和功能的必要性，因为这些见解可以为治疗过敏性疾病所急需的创新疗法铺平道路。

引用次数: 0

In vitro cross-reactivity between hen's egg and quail's egg in children with hen's egg allergy 对母鸡蛋过敏的儿童对母鸡蛋和鹌鹑蛋的体外交叉反应。

IF 6.2 2区医学 Q1 ALLERGY

Allergology International

Pub Date : 2025-01-01 DOI: 10.1016/j.alit.2024.07.006

Mari Takei, Masatoshi Mitomori, Akemi Saito, Kinji Tada, Noriyuki Yanagida, Sakura Sato, Motohiro Ebisawa

引用次数: 0

Long term safety and efficacy of ligelizumab in the treatment of Japanese patients with chronic spontaneous urticaria 利格珠单抗治疗日本慢性自发性荨麻疹患者的长期安全性和有效性。

IF 6.2 2区医学 Q1 ALLERGY

Allergology International

Pub Date : 2025-01-01 DOI: 10.1016/j.alit.2024.09.002

Hidetoshi Takahashi , Atsushi Fukunaga , Koremasa Hayama , Takayoshi Sasajima , Ayako Fujishige , Ryohei Ichishita , Naoko Tomimatsu , Eva Hua , Vineeth Varanasi , Alis Burciu , Michihiro Hide , Thomas Severin

Background

In Japan, urticaria is a common skin disorder with chronic spontaneous urticaria (CSU) being the most frequent subtype. This study evaluated the safety of ligelizumab (anti-IgE monoclonal antibody) in Japanese CSU patients.

Methods

This was a Phase 3 multicenter, open-label, single-arm 52-week study in adult Japanese patients with CSU inadequately controlled with locally approved doses of H1-antihistamines. The primary objective reported the safety of ligelizumab 120 mg subcutaneously every 4 weeks, by evaluation of treatment emergent adverse events (TEAE). Secondary objectives evaluated efficacy by absolute change from baseline (CFB) in weekly urticaria activity score (UAS7), and the proportion of patients with UAS7 = 0, and dermatology life quality index (DLQI) = 0–1 over time.

Results

From a total of 66 CSU patients (80.3% females; mean ± SD age 46.4 ± 13.2 years; mean ± SD baseline UAS7 28.7 ± 6.5) enrolled, 53 patients (80.3%) reported ≥1 TEAE during the study, with no severe or serious adverse events, no anaphylaxis events and low frequency of TEAEs leading to treatment discontinuations (6.1%). Absolute mean CFB of UAS7 showed a rapid onset of response at Week 4 (−14.2) with further improvement until end of treatment at Week 52 (−22.9). The proportion of patients achieving UAS7 = 0 improved over time (14.5% at Week 4; 50.0% at Week 52). A sizable proportion of patients achieved DLQI 0–1 with the first dose of ligelizumab (38.5%), and improvements observed throughout the study until Week 52 (68.8%).

Conclusions

Treatment with ligelizumab 120 mg was well-tolerated with mild to moderate adverse events and was efficacious in Japanese patients.

背景：在日本，荨麻疹是一种常见的皮肤疾病，其中慢性自发性荨麻疹（CSU）是最常见的亚型。本研究评估了利格珠单抗（抗 IgE 单克隆抗体）在日本 CSU 患者中的安全性：这是一项为期52周的3期多中心、开放标签、单臂研究，研究对象为使用当地批准剂量的H1-抗组胺药物治疗效果不佳的日本成年CSU患者。研究的首要目标是通过评估治疗突发不良事件（TEAE）来评价利格珠单抗120毫克皮下注射每4周一次的安全性。次要目标通过每周荨麻疹活动评分（UAS7）与基线（CFB）相比的绝对值变化、UAS7=0的患者比例以及皮肤科生活质量指数（DLQI）=0-1来评估疗效：共有66名CSU患者（80.3%为女性；平均（±SD）年龄为46.4±13.2岁；平均（±SD）基线UAS7为28.7±6.5）参加了研究，其中53名患者（80.3%）在研究期间报告了≥1次TEAE，无严重不良事件，无过敏性休克事件，导致治疗中断的TEAE发生率较低（6.1%）。UAS7的绝对平均CFB在第4周（-14.2）出现快速反应，并在第52周（-22.9）治疗结束前进一步改善。随着时间的推移，达到 UAS7 = 0 的患者比例有所提高（第 4 周为 14.5%；第 52 周为 50.0%）。相当大比例的患者在首次服用利格珠单抗时达到了DLQI 0-1（38.5%），在整个研究过程中一直到第52周均有所改善（68.8%）：利格珠单抗120毫克对日本患者的耐受性良好，不良反应轻微至中等，疗效显著。

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引用次数: 0

3D-CT-derived lung volumes and mortality risk in patients with fibrotic hypersensitivity pneumonitis 纤维化超敏性肺炎患者的三维 CT 导出肺容积和死亡风险。

IF 6.2 2区医学 Q1 ALLERGY

Allergology International

Pub Date : 2025-01-01 DOI: 10.1016/j.alit.2024.07.002

Shusuke Yazawa , Yuzo Suzuki , Yuko Tanaka , Koshi Yokomura , Masato Kono , Dai Hashimoto , Atsuki Fukada , Yusuke Inoue , Hideki Yasui , Hironao Hozumi , Masato Karayama , Kazuki Furuhashi , Noriyuki Enomoto , Tomoyuki Fujisawa , Naoki Inui , Takafumi Suda

Background

Hypersensitivity pneumonitis (HP) is a complex and heterogenous interstitial lung disease (ILD) that occurs in susceptible individuals due to certain inhaled antigens. Fibrotic-HP is a major underlying disease of progressive pulmonary fibrosis. Therefore, in addition to the radiological features of HP, quantitatively measuring fibrosis is important to evaluate disease severity and progression. The present study aimed to compare three-dimensional computed tomography (3D-CT)-derived lung volumes (LVs) of patients with HP and determine its association with mortality risk.

Methods

In this retrospective and multicenter cohort study, 126 patients diagnosed with HP (fibrotic, n = 72 and non-fibrotic, n = 54) with a confidence level higher than moderate were enrolled. Each lobe LV was measured using 3D-CT at the time of diagnosis and standardized using predicted forced vital capacity. The 3D-CT LV was compared with those of 42 controls and 140 patients with idiopathic pulmonary fibrosis (IPF).

Results

Compared to patients with fibrotic-HP, the standardized total LV was significantly higher in controls and patients with non-fibrotic-HP and was similar in patients with IPF. Longitudinal analyses demonstrated that approximately half of the patients with fibrotic-HP had an annual decrease in total LV. Decreased total and lower-lobe LVs were associated with shorter survival, and were independently associated with mortality together with ongoing exposure to inciting antigens. A composite model consisting of ongoing exposure to inciting antigens and total or lower-lobe LV successfully classified mortality risk into three groups.

Conclusions

Quantitatively measuring standardized LV can help determine disease severity, progression, and mortality risk in patients with fibrotic-HP.

背景：超敏性肺炎（HP）是一种复杂的异质性间质性肺病（ILD），易感者因吸入某些抗原而发病。纤维化性肺炎是进行性肺纤维化的主要基础疾病。因此，除了 HP 的放射学特征外，纤维化的定量测量对于评估疾病的严重程度和进展也很重要。本研究旨在比较三维计算机断层扫描（3D-CT）得出的HP患者肺容积（LV），并确定其与死亡风险的关系：在这项回顾性多中心队列研究中，共纳入了126名确诊为HP（纤维化，72人；非纤维化，54人）且置信度高于中度的患者。在诊断时使用 3D-CT 测量了每个肺叶的左心室，并使用预测的用力肺活量进行了标准化。将 3D-CT 左心室与 42 例对照组和 140 例特发性肺纤维化（IPF）患者的左心室进行比较：结果：与纤维化-HP 患者相比，对照组和非纤维化-HP 患者的标准化总左心室明显更高，而 IPF 患者的总左心室与之相似。纵向分析表明，约半数纤维化-高血压患者的总左心室容量每年都在下降。总左心室和下叶左心室缩小与生存期缩短有关，并且与持续暴露于诱发抗原的死亡率独立相关。由持续暴露于诱发抗原和总左心室或下叶左心室组成的复合模型成功地将死亡风险分为三组：定量测量标准化左心室有助于确定纤维化肝病患者的疾病严重程度、进展和死亡风险。

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引用次数: 0

Comprehensive review of pollen-food allergy syndrome: Pathogenesis, epidemiology, and treatment approaches 花粉-食物过敏综合征综述：发病机制、流行病学和治疗方法。

IF 6.2 2区医学 Q1 ALLERGY

Allergology International

Pub Date : 2025-01-01 DOI: 10.1016/j.alit.2024.08.007

Yukinori Kato, Taiyo Morikawa, Shigeharu Fujieda

Pollen-food allergy syndrome (PFAS) is caused by cross-reaction of a specific pollen antigen with the corresponding food allergen in sensitized individuals. The manifestations are usually limited to oral symptoms; however, sometimes, rhinitis, respiratory and skin symptoms, and anaphylactic shock may occur. In PFAS pathogenesis, when food containing protein antigens (pan-allergens) with high homology to pollen antigens is ingested, mast cells bound to pollen antigen-specific IgE distributed in the oral mucosa cross-react with the food antigen, causing a local type I allergic reaction. The prevalence of PFAS depends on the geographic conditions, such as the type and amount of pollen in the area. PFAS is prevalent in all regions owing to the wide variety of pollen antigens implicated in the disease, such as alder and grass pollen, even outside of the birch habitat area. Basic research on PFAS is expected to significantly contribute to elucidating the pathogenesis and development of therapeutic strategies for PFAS. Currently, effective treatment for patients with PFAS that allows safe consumption of raw foods is lacking, and avoiding the intake of causative foods is the basis of prevention. Furthermore, allergen immunotherapy for PFAS has not yet been established, but various attempts are underway to develop it into a novel treatment strategy. This review highlights the current research landscape on the pathophysiology, epidemiology, and clinical aspects of PFAS. We outline the research gaps that should be addressed to improve the outcomes of patients with PFAS.

花粉-食物过敏综合征（PFAS）是由过敏体质的人体内特定花粉抗原与相应食物过敏原发生交叉反应引起的。其表现通常仅限于口腔症状，但有时也会出现鼻炎、呼吸道和皮肤症状以及过敏性休克。在 PFAS 的发病机制中，当摄入含有与花粉抗原高度同源性的蛋白质抗原（泛过敏原）的食物时，与分布在口腔黏膜中的花粉抗原特异性 IgE 结合的肥大细胞会与食物抗原发生交叉反应，引起局部 I 型过敏反应。PFAS 的流行程度取决于地理条件，如该地区花粉的种类和数量。由于与该病有关的花粉抗原种类繁多，如桤木花粉和草花粉，因此 PFAS 在所有地区都很普遍，甚至在桦树栖息地以外的地区也是如此。有关 PFAS 的基础研究有望为阐明 PFAS 的发病机制和制定治疗策略做出重大贡献。目前，还缺乏针对 PFAS 患者的有效治疗方法，使其能够安全食用生食，而避免摄入致病食物是预防的基础。此外，针对 PFAS 的过敏原免疫疗法尚未确立，但人们正在进行各种尝试，以将其发展成一种新型治疗策略。本综述重点介绍了目前有关全氟辛烷磺酸的病理生理学、流行病学和临床方面的研究情况。我们概述了为改善 PFAS 患者的治疗效果而应填补的研究空白。

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引用次数: 0

Dysbiosis of the human skin mycobiome in patients receiving systemic IL-23 inhibitors 接受全身性 IL-23 抑制剂治疗的患者皮肤真菌生物群的菌群失调。

IF 6.2 2区医学 Q1 ALLERGY

Allergology International

Pub Date : 2025-01-01 DOI: 10.1016/j.alit.2024.06.003

Yuta Koike , Sayaka Kuwatsuka , Daisuke Motooka , Hiroyuki Murota

Background

Systemic inhibition of pro-inflammatory cytokines affects the skin microbiome; however, the impact of systemic anti-inflammatory therapy on the skin fungal microbiome is poorly understood. To examine the effects of cytokine inhibition on the fungal community on human skin and oral mucosa, we analyzed the composition of the skin mycobiome before and after IL-23 inhibition.

Methods

The study enrolled 15 psoriasis patients. Swab samples were collected from the psoriasis-free skin of antecubital fossa, post-auricular, and the tongue surface before and after 16 weeks of treatment with anti-IL-23 antibodies. Fungal DNA was sequenced by ITS1 metagenomic analysis, and taxonomic classification was performed.

Results

Data from samples collected from the antecubital fossa revealed that the α diversity of the skin mycobiome decreased significantly after treatment with anti-IL-23 antibodies (p = 0.0120). Fungal DNAs were not amplified in 6/15 swab samples after 16 weeks of IL-23 inhibition; by contrast, sufficiently detected in all 15 samples before treatment (p = 0.0554). A comparison of 9/15 paired samples containing well-detected reads revealed that the percentage of genus Malassezia in the mycobiome fell significantly after treatment with IL-23 inhibitors (before, 29.3% ± 9.9%; after; 8.5% ± 3.4%, p = 0.0137). The mycobiome on post-auricular skin and on the tongue surface showed no marked changes after IL-23 inhibition.

Conclusions

Taken together, the data suggest that inhibition of systemic IL-23 provokes dysbiosis of the mycobiome at the antecubital fossa skin, a finding characterized by reduced fungal diversity and a reduction in the percentage of the genus Malassezia.

背景：全身性抑制促炎细胞因子会影响皮肤微生物组；然而，全身性抗炎疗法对皮肤真菌微生物组的影响却知之甚少。为了研究细胞因子抑制对人体皮肤和口腔粘膜真菌群落的影响，我们分析了抑制 IL-23 前后皮肤真菌生物群的组成：方法：本研究共招募了 15 名银屑病患者。在使用抗 IL-23 抗体治疗 16 周之前和之后，从无银屑病的眶前窝、耳后和舌面皮肤采集拭子样本。通过 ITS1 元基因组分析对真菌 DNA 进行了测序，并进行了分类：结果：从眶前窝采集的样本数据显示，使用抗IL-23抗体治疗后，皮肤真菌生物群的α多样性显著下降（p = 0.0120）。在抑制IL-23 16周后，6/15个拭子样本中的真菌DNA没有扩增；相比之下，在治疗前的所有15个样本中都能充分检测到真菌DNA（p = 0.0554）。对含有充分检测读数的 9/15 份配对样本进行比较后发现，在使用 IL-23 抑制剂治疗后，马拉色菌属在真菌生物群中所占的比例显著下降（治疗前：29.3% ± 9.9%；治疗后：8.5% ± 3.4%，p = 0.0137）。IL-23抑制剂治疗后，耳后皮肤和舌头表面的霉菌生物群没有发生明显变化：综上所述，这些数据表明，抑制全身性 IL-23 会导致眶前窝皮肤真菌生物群失调，其特征是真菌多样性减少，马拉色菌属比例降低。

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引用次数: 0

Reliability of image-based morphometry of the bronchial tree 基于图像的支气管树形态测量的可靠性。

IF 6.2 2区医学 Q1 ALLERGY

Allergology International

Pub Date : 2025-01-01 DOI: 10.1016/j.alit.2024.07.009

Hiroko Kitaoka , Takashi Kijima

引用次数: 0

T follicular helper cells and IgE T滤泡辅助细胞和IgE。

IF 6.2 2区医学 Q1 ALLERGY

Allergology International

Pub Date : 2025-01-01 DOI: 10.1016/j.alit.2024.12.001

Yusei Ohshima (Associate Editor, Allergology International)

引用次数: 0

Critical pathomechanisms of NSAID-exacerbated respiratory disease (N-ERD) clarified by treatment with omalizumab, an anti-IgE antibody 用抗 IgE 抗体奥马珠单抗治疗非甾体抗炎药导致的呼吸道疾病（N-ERD）的关键病理机制。

IF 6.2 2区医学 Q1 ALLERGY

Allergology International

Pub Date : 2025-01-01 DOI: 10.1016/j.alit.2024.08.008

Hiroaki Hayashi , Makoto Ishii , Yoshinori Hasegawa , Masami Taniguchi

Characteristic symptoms of NSAID-exacerbated respiratory disease (N-ERD) include asthma, chronic eosinophilic rhinosinusitis with nasal polyposis, cysteinyl LT (CysLT) overproduction and NSAIDs hypersensitivity. Some N-ERD patients present with episodic treatment-resistant extra-respiratory symptoms (CysLT-associated coronary artery vasospasm, gastroenteritis, or skin rash). Even when using standard treatments for respiratory and extra-respiratory symptoms, including systemic corticosteroids and aspirin desensitization, it is difficult to control the clinical symptoms and severe type 2 inflammation involved with mast cells, eosinophils, ILC2s, and platelet activation. Few treatment options are applicable in a clinical setting. Therefore, identifying effective treatments is essential for managing N-ERD patients who suffer from these conditions. Our previous observational study demonstrated 12-month omalizumab treatment of N-ERD was clinically effective against respiratory symptoms. Despite the remaining eosinophilia, omalizumab significantly reduced urinary LTE₄ and PGD₂ metabolites to near normal levels at steady state. Based on the preliminary study, we demonstrated that omalizumab induced tolerance to aspirin in N-ERD patients 3 months after therapy initiation and suppressed activation of mast cells during 24 h of initiation in a randomized manner. Moreover, omalizumab had significant efficacy against extra-respiratory symptoms at baseline (lacking aspirin exposure) as well as throughout aspirin challenge. This review addresses the latest discoveries related to N-ERD pathogenesis and the significant effectiveness of omalizumab on N-ERD as a mast cell stabilizer. Our findings regarding omalizumab-associated mast cell inhibitory effects are indirect evidence that mast cell dysregulation and, possibly, IgE are pivotal components of N-ERD.

非甾体抗炎药加重呼吸道疾病（N-ERD）的特征性症状包括哮喘、慢性嗜酸性鼻炎伴鼻息肉、半胱氨酸LT（CysLT）分泌过多和对非甾体抗炎药过敏。一些 N-ERD 患者会出现发作性治疗耐药的呼吸道外症状（与 CysLT 相关的冠状动脉血管痉挛、肠胃炎或皮疹）。即使对呼吸道症状和呼吸道外症状采用标准治疗方法（包括全身皮质类固醇和阿司匹林脱敏），也很难控制临床症状以及肥大细胞、嗜酸性粒细胞、ILC2s 和血小板活化引起的严重 2 型炎症。适用于临床的治疗方案寥寥无几。因此，找到有效的治疗方法对于管理患有这些病症的 N-ERD 患者至关重要。我们之前的观察性研究表明，对 N-ERD 患者进行为期 12 个月的奥马珠单抗治疗对缓解呼吸道症状有临床疗效。尽管仍存在嗜酸性粒细胞增多，但奥马珠单抗能显著降低尿液中的 LTE4 和 PGD2 代谢物，使其在稳态时接近正常水平。根据初步研究，我们证明奥马珠单抗可诱导 N-ERD 患者在开始治疗 3 个月后对阿司匹林产生耐受性，并以随机方式抑制开始治疗 24 小时内肥大细胞的活化。此外，奥马珠单抗对基线（未接触阿司匹林）和整个阿司匹林挑战期间的呼吸道外症状都有显著疗效。这篇综述探讨了与 N-ERD 发病机制有关的最新发现，以及奥马珠单抗作为肥大细胞稳定剂对 N-ERD 的显著疗效。我们关于奥马珠单抗相关肥大细胞抑制作用的发现间接证明了肥大细胞失调以及 IgE 可能是 N-ERD 的关键组成部分。

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引用次数: 0