Clinical and Translational Allergy最新文献_第5页

Early Changes in House Dust Mite Component Specific Immunoglobulin Levels Predict the One-Year Efficacy of Allergen Immunotherapy in Patients With Allergic Rhinitis 屋尘螨成分特异性免疫球蛋白水平的早期变化预测变应性鼻炎患者过敏原免疫治疗的一年疗效

IF 4 2区医学 Q2 ALLERGY

Clinical and Translational Allergy

Pub Date : 2025-09-08 DOI: 10.1002/clt2.70099

Shuying Li, Yue Ma, Jiaying Li, Xian Feng, Fang Xiong, Miaomiao Han, Huabin Li, Hongfei Lou

Background

The efficacy of subcutaneous immunotherapy (SCIT) in allergic rhinitis (AR) patients varies. Component-resolved diagnostics (CRD) may serve as a useful tool to predict therapeutic responses.

Methods

Forty-three house dust mite (HDM)-sensitized AR patients undergoing SCIT were enrolled. Clinical data and serum samples were collected at baseline (V1), 15 weeks (V2), and 1 year (V3). The levels of specific immunoglobulin E (sIgE) and sIgG4 to nine HDM components were measured, and a predictive model was established. An independent prospective cohort of 23 patients was used for validation.

Results

The most prevalent sensitizing components were Dermatophagoides pteronyssinus (Der p) 1, Dermatophagoides farinae (Der f) 1, Der p 2, Der f 2, and Der p 23. The responders had a significantly higher Combined Symptom and Medication Score (CSMS) at baseline than did the nonresponders. At V2, the responders showed a greater increase in serum levels of Der f 1 sIgE, higher levels of Der p 23 sIgG4, and greater incremental changes in Der p 23 sIgG4 levels. A composite model based on V1 CSMS, ∆_15w Der f 1 sIgE, and ∆_15w Der p 23 sIgG4 achieved an area under the receiver operating characteristic curve (AUC) of 0.896 (cutoff: 0.455), with 83.3% sensitivity and 84.0% specificity. In the validation cohort, the model showed a 75.0% positive predictive value, 86.7% negative predictive value, and 82.6% overall accuracy.

Conclusion

A composite biomarker model based on HDM component responses enabled early prediction of SCIT efficacy, supporting more personalized treatment strategies for AR management.

背景皮下免疫治疗（SCIT）对变应性鼻炎（AR）患者的疗效各不相同。成分解析诊断（CRD）可以作为预测治疗反应的有用工具。方法对43例屋尘螨（HDM）致敏AR患者行SCIT治疗。在基线（V1）、15周（V2）和1年（V3）收集临床资料和血清样本。测定9种HDM成分的特异性免疫球蛋白E （sIgE）和sIgG4水平，并建立预测模型。一项由23名患者组成的独立前瞻性队列研究用于验证。结果最常见的致敏成分为翼状螨（Der p） 1、粉状螨（Der f） 1、Der p2、Der f2和Der p23。应答者在基线时的综合症状和药物评分（CSMS）明显高于无应答者。在V2时，应答者血清中Der f1 sIgE水平升高，Der p23 sIgG4水平升高，Der p23 sIgG4水平增加。基于V1 csm、∆15w Der f 1 sIgE和∆15w Der p 23 sIgG4的复合模型的受试者工作特征曲线下面积（AUC）为0.896（截止值为0.455），敏感性为83.3%，特异性为84.0%。在验证队列中，该模型的阳性预测值为75.0%，阴性预测值为86.7%，总体准确率为82.6%。结论基于HDM成分反应的复合生物标志物模型可以早期预测SCIT疗效，为AR管理提供更个性化的治疗策略。

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引用次数: 0

Subcutaneous Allergen-Specific Immunotherapy for Allergic Rhinitis: Divergent IgA Responses in Nasal Mucosa and Blood With Validation of B Cell Class-Switching in Lymph Nodes and Blood 变应性鼻炎的皮下过敏原特异性免疫治疗：鼻黏膜和血液中不同的IgA反应与淋巴结和血液中B细胞类型转换的验证

IF 4 2区医学 Q2 ALLERGY

Clinical and Translational Allergy

Pub Date : 2025-09-02 DOI: 10.1002/clt2.70097

Maryam Jafari, Marianne Petro, Eirini Paziou, Eric Hjalmarsson, Agnetha Karlsson, Monika Ezerskyte, Laila Hellkvist, Susanna Kumlien Georén, Eduardo I. Cardenas, Lars-Olaf Cardell

Background

Subcutaneous immunotherapy (SCIT) has been a cornerstone treatment for allergic rhinitis (AR) for over 50 years, consistently demonstrating symptom reduction and modulation of immune responses. Despite this, the underlying mechanisms responsible for the efficacy of SCIT remain incompletely understood, especially with regard to local immune responses in lymph nodes and nasal mucosa.

Aim

To determine the impact of SCIT treatment on immunoglobulin production in blood and nasal mucosa, as well as B cell class-switching in blood and lymph nodes.

Methodology

Blood, nasal lavage (NAL), and fine-needle aspirates (FNA) of inguinal lymph nodes were collected from 23 patients with birch and/or timothy pollen-induced AR before and after SCIT updosing. General response to SCIT was evaluated with symptom and medication scores, as well as allergen-mediated activation of basophils. Allergen-specific IgE, IgA, IgG, and IgG4 were measured in blood and NAL via ELISA. B-cell class-switching was assessed in blood and FNAs by flow cytometry.

Results

AR symptoms, medication use, and basophil sensitivity to allergens was reduced after SCIT updosing. Interestingly, the plasma levels of allergen-specific IgA, IgG, and IgG4 increased after SCIT updosing, while the levels of allergen-specific IgE and IgA decreased in NAL at this timepoint. Moreover, these results were accompanied by an increase in conventional (IgD⁻CD27⁺) and unconventional (IgD⁻CD27⁻) memory B cells in blood and lymph nodes, respectively.

Conclusion

This study highlights the differential effects of SCIT on local and systemic immunity and identifies early immunological changes associated with treatment. However, confirmation of long-term tolerance will require extended follow-up, including in-season analyses. The local decrease in allergen-specific IgA in NAL, alongside a systemic increase in allergen-specific IgA and IgG4, underscores the importance of assessing both mucosal and systemic responses when evaluating SCIT efficacy.

50多年来，皮下免疫治疗（SCIT）一直是变应性鼻炎（AR）的基础治疗方法，一直显示出症状减轻和免疫反应调节。尽管如此，SCIT疗效的潜在机制仍然不完全清楚，特别是关于淋巴结和鼻黏膜的局部免疫反应。目的探讨SCIT治疗对血液和鼻黏膜免疫球蛋白产生以及血液和淋巴结B细胞类型转换的影响。方法收集23例白桦和/或timothym花粉诱导的AR患者在SCIT治疗前后的血液、鼻灌洗（NAL）和腹股沟淋巴结细针抽吸（FNA）。通过症状和药物评分以及过敏原介导的嗜碱性粒细胞激活来评估对SCIT的一般反应。采用ELISA法检测血液和NAL中过敏原特异性IgE、IgA、IgG和IgG4。通过流式细胞术评估血液和FNAs中b细胞的类别转换。结果服用SCIT后，AR症状、药物使用和嗜碱性粒细胞对过敏原的敏感性均有所降低。有趣的是，SCIT增加后，血浆中过敏原特异性IgA、IgG和IgG4水平升高，而NAL中过敏原特异性IgE和IgA水平在此时间点下降。此外，这些结果还伴随着血液和淋巴结中常规（IgD - CD27+）和非常规（IgD - CD27−）记忆B细胞的增加。结论：本研究强调了SCIT对局部和全身免疫的不同影响，并确定了与治疗相关的早期免疫变化。然而，确认长期耐受性需要延长随访时间，包括季节分析。NAL中过敏原特异性IgA的局部减少，以及过敏原特异性IgA和IgG4的全身性增加，强调了在评估SCIT疗效时评估粘膜和全身反应的重要性。

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引用次数: 0

Characterization of Chronic Rhinosinusitis Patients Based on Markers of Type 2 Inflammation: Findings From the European CRS Outcome Registry (CHRINOSOR) 基于2型炎症标志物的慢性鼻窦炎患者特征：来自欧洲CRS结局登记（CHRINOSOR）的发现

IF 4 2区医学 Q2 ALLERGY

Clinical and Translational Allergy

Pub Date : 2025-08-31 DOI: 10.1002/clt2.70095

Carlo Cavaliere, Sven F. Seys, Joost de Kinderen, Giulia Bettio, Alexandros Andrianakis, Isam Alobid, Peter W. Hellings, Laura Van Gerven, Valérie Hox, Claire Hopkins, Anette Kjeldsen, Sietze Reitsma, Sven Schneider, Peter-Valentin Tomazic, Zuzana Diamant, Julia Eckl-Dorna, Wytske J. Fokkens, Clemens Holzmeister, Kenneth Larsen, Anu Laulajainen-Hongisto, Antonella Loperfido, Valerie Lund, Gert Mariën, Simonetta Masieri, Geoffrey Mortuaire, Mathilde Moyaert, Joaquim Mullol, Josje Otten, Camilo Rodriquez-Van Strahlen, Martin Wagenmann, Claus Bachert

Background

Primary chronic rhinosinusitis (CRS) can be classified based on the sinuses involved and the dominant endotype of the mucosal inflammation. Since the introduction of type 2 targeted biologics as treatment option for CRS, assessment of the inflammatory status has gained importance in CRS patients. We here aimed to characterize CRS patients with and without elevated markers of type 2 inflammation.

Methods

CRS patients who visited the outpatient ENT clinic in one of the 10 tertiary centers in 7 European countries were invited to use the Galenus Health mobile application for the monitoring of their disease.

Results

CRS patients (n = 281) were stratified according to blood eosinophil counts or BEC (< 150 cells/μL: 21.6% of patients, ≥ 150 cells/μL: 78.4%; < 250 cells/μL: 36.3%, ≥ 250 cells/μL: 63.7%) and serum total IgE (< 100 IU/mL: 59.9%, ≥ 100 IU/mL: 40.1%). BEC and serum total IgE did not correlate well (Spearman r = 0.06; p = 0.39). CRS patients with BEC ≥ 150 cell/μL or ≥ 250 cells/μL, respectively, showed increased NPS, SNOT-22, VAS for total CRS symptoms, loss of smell, nasal blockage, runny nose compared to patients with BEC below 150 or 250 cells/μL. CRS patients with increased serum total IgE (≥ 100 IU/mL) did not show differences in the outcome parameters compared to patients with levels below 100 IU/mL. CRS patients with asthma (58.9%) showed increased SNOT-22 and VAS loss of smell compared to patients without asthma.

Conclusions

A significant proportion of CRS patients exhibit a type 2 endotype, characterized by blood eosinophilia (78%), increased serum total IgE (40%) and/or concomitant asthma (59%). Our results underline the usefulness of eosinophils as a marker of type 2 inflammation and severity but challenge the utility of serum total IgE since it does not correlate with any of the markers of severity.

背景原发性慢性鼻窦炎（CRS）可根据受累的鼻窦和粘膜炎症的主要内型进行分类。自从引入2型靶向生物制剂作为CRS的治疗选择以来，炎症状态的评估在CRS患者中变得越来越重要。我们在这里的目的是表征伴有和不伴有2型炎症标志物升高的CRS患者。方法邀请在欧洲7个国家的10个三级中心之一的门诊就诊的CRS患者使用Galenus Health移动应用程序对其疾病进行监测。结果281例CRS患者按血嗜酸性粒细胞计数或BEC （<； 150细胞/μL: 21.6%，≥150细胞/μL: 78.4%; <； 250细胞/μL: 36.3%，≥250细胞/μL: 63.7%）和血清总IgE （< 100 IU/mL: 59.9%,≥100 IU/mL: 40.1%）分层。BEC与血清总IgE相关性不佳（Spearman r = 0.06; p = 0.39）。与BEC低于150或250 cells/μL的CRS患者相比，BEC≥150或250 cells/μL的CRS患者在总CRS症状、嗅觉丧失、鼻塞、流鼻涕方面的NPS、SNOT-22、VAS均增加。血清总IgE升高（≥100 IU/mL）的CRS患者与低于100 IU/mL的患者相比，结果参数没有差异。伴有哮喘的CRS患者（58.9%）与无哮喘患者相比，SNOT-22和VAS嗅觉丧失增加。结论：相当比例的CRS患者表现为2型内型，其特征为血嗜酸性粒细胞增多（78%），血清总IgE升高（40%）和/或合并哮喘（59%）。我们的研究结果强调了嗜酸性粒细胞作为2型炎症和严重程度标记物的有效性，但挑战了血清总IgE的实用性，因为它与任何严重程度标记物都不相关。

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引用次数: 0

Evaluation of Diagnosis, Cross-Reactivity, and Risk Factors in Pediatric Patients With Macrolide Allergy 大环内酯类药物过敏儿童的诊断、交叉反应和危险因素评估

IF 4 2区医学 Q2 ALLERGY

Clinical and Translational Allergy

Pub Date : 2025-08-26 DOI: 10.1002/clt2.70096

Güler Yıldırım, Merve Karaca Şahin, Nilay Çalışkan, Hamit Boloğur, Muhammed Fatih Erbay, Hilal Güngör, Şefika İlknur Kökçü Karadağ, Aslı Berivan Topçak, Deniz Özçeker

Background

Macrolide antibiotics are generally considered safe in children, but allergic reactions can still occur. This study aims to evaluate the sensitivity and specificity of intradermal test (IDT) used to detect macrolide allergy in pediatric patients, investigate the rate of cross-reactivity between clarithromycin and azithromycin, and identify factors influencing the development of macrolide allergy.

Methods

A total of 102 patients with suspected clarithromycin and azithromycin allergy were included in the study. Characteristics of the reactions and results of skin and drug oral provocation test (OPT) were recorded.

Results

Clarithromycin was confirmed as the culprit drug in 8 (9%) of 88 patients, and azithromycin in 1 (7.1%) of 14 patients. The cross-reactivity between clarithromycin and azithromycin determined 11.1%. In patients with immediate-type reactions, IDT performed at a concentration of 0.05 mg/mL demonstrated a sensitivity of 33.3% (95% CI: 0.0%–66.7%) and a specificity of 92.7% (95% CI: 82.9%–100%). When a higher concentration of 0.5 mg/mL was used, sensitivity increased to 100% (95% CI: 0.0%–100%), while specificity decreased to 78.9% (95% CI: 65.8%–92.1%) respectively. According to univariate logistic regression analysis, patients with a history of previous non-macrolide drug allergy (p: 0.003, Odds Ratio [OR]: 41, 95% CI: 3.6–456.5) and family history of drug allergy (p = 0.026, OR: 5.2, 95% CI: 1.2–22.5) were at a significantly higher risk of developing macrolide allergy.

Conclusions

Although IDT at a concentration of 0.05 mg/mL showed higher specificity (92.7%) compared to 0.5 mg/mL (78.9%), given its limited sensitivity, OPT is still required to confirm the diagnosis.

大环内酯类抗生素通常被认为对儿童是安全的，但仍可能发生过敏反应。本研究旨在评价皮内试验（IDT）检测儿科大环内酯类药物过敏的敏感性和特异性，探讨克拉霉素与阿奇霉素的交叉反应率，探讨影响大环内酯类药物过敏发展的因素。方法选取102例疑似克拉霉素和阿奇霉素过敏患者作为研究对象。记录反应特点及皮肤和药物口服激发试验（OPT）结果。结果88例患者中克拉霉素占8例（9%），14例中阿奇霉素占1例（7.1%）。克拉霉素与阿奇霉素的交叉反应率为11.1%。在立即型反应患者中，0.05 mg/mL浓度的IDT敏感性为33.3% (95% CI: 0.0%-66.7%)，特异性为92.7% （95% CI: 82.9%-100%）。当使用更高浓度的0.5 mg/mL时，灵敏度增加到100% (95% CI: 0.0% ~ 100%)，特异性下降到78.9% （95% CI: 65.8% ~ 92.1%）。单因素logistic回归分析显示，既往有非大环内酯类药物过敏史（p: 0.003，比值比[OR]: 41, 95% CI: 3.6 ~ 456.5）和有药物过敏家族史（p = 0.026, OR: 5.2, 95% CI: 1.2 ~ 22.5）的患者发生大环内酯类药物过敏的风险显著增高。结论0.05 mg/mL浓度的IDT特异性为92.7%，高于0.5 mg/mL浓度的78.9%，但由于其敏感性有限，仍需要OPT来确诊。

{"title":"Evaluation of Diagnosis, Cross-Reactivity, and Risk Factors in Pediatric Patients With Macrolide Allergy","authors":"Güler Yıldırım, Merve Karaca Şahin, Nilay Çalışkan, Hamit Boloğur, Muhammed Fatih Erbay, Hilal Güngör, Şefika İlknur Kökçü Karadağ, Aslı Berivan Topçak, Deniz Özçeker","doi":"10.1002/clt2.70096","DOIUrl":"https://doi.org/10.1002/clt2.70096","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Macrolide antibiotics are generally considered safe in children, but allergic reactions can still occur. This study aims to evaluate the sensitivity and specificity of intradermal test (IDT) used to detect macrolide allergy in pediatric patients, investigate the rate of cross-reactivity between clarithromycin and azithromycin, and identify factors influencing the development of macrolide allergy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 102 patients with suspected clarithromycin and azithromycin allergy were included in the study. Characteristics of the reactions and results of skin and drug oral provocation test (OPT) were recorded.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Clarithromycin was confirmed as the culprit drug in 8 (9%) of 88 patients, and azithromycin in 1 (7.1%) of 14 patients. The cross-reactivity between clarithromycin and azithromycin determined 11.1%. In patients with immediate-type reactions, IDT performed at a concentration of 0.05 mg/mL demonstrated a sensitivity of 33.3% (95% CI: 0.0%–66.7%) and a specificity of 92.7% (95% CI: 82.9%–100%). When a higher concentration of 0.5 mg/mL was used, sensitivity increased to 100% (95% CI: 0.0%–100%), while specificity decreased to 78.9% (95% CI: 65.8%–92.1%) respectively. According to univariate logistic regression analysis, patients with a history of previous non-macrolide drug allergy (<i>p</i>: 0.003, Odds Ratio [OR]: 41, 95% CI: 3.6–456.5) and family history of drug allergy (<i>p</i> = 0.026, OR: 5.2, 95% CI: 1.2–22.5) were at a significantly higher risk of developing macrolide allergy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Although IDT at a concentration of 0.05 mg/mL showed higher specificity (92.7%) compared to 0.5 mg/mL (78.9%), given its limited sensitivity, OPT is still required to confirm the diagnosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Implementation of Rapid Drug Desensitization in Antineoplastic Drug Therapy in Denmark Using One-Bag Protocols 丹麦使用一袋方案在抗肿瘤药物治疗中快速脱敏的实施

IF 4 2区医学 Q2 ALLERGY

Clinical and Translational Allergy

Pub Date : 2025-08-13 DOI: 10.1002/clt2.70093

Trine Holm Rasmussen, Charlotte Gotthard Mortz, Per Pfeiffer, Nina Andersen, David George Mawn, Line Kring Tannert, Millie Nguyen Basu, Helene Marlies Rasmussen, Carsten Bindslev-Jensen

Background

Rapid drug desensitization (RDD) is the cornerstone of managing patients with immediate drug hypersensitivity reactions (IDHR) to antineoplastic drugs in Southern Europe and the United States. As the first in Northern Europe, an allergy treatment program that includes RDD and drug provocation testing (DPT) was implemented for Danish patients with cancer. We report the results of this allergy intervention, the number of successful treatments, the fraction, timing and severity of breakthrough reactions (BTR) and the actual treatment duration of RDD procedures.

Methods

This was a prospective observational study. Patients with IDHRs to antineoplastic drugs referred to the allergy treatment program were included. Patients were followed up until finalization of DPT and/or RDD. RDDs were performed according to one-bag RDD-protocols with drug concentrations strictly following manufacturer's instructions and infusion sets primed with flushing fluid. The outcome of DPTs and RDDs were recorded together with detailed information on BTRs and treatment duration of RDD-procedures.

Results

During 28 months, 72 patients were included. With DPT, a safe drug alternative was found for five drugs, hypersensitivity was ruled out for six, and one treatment was discontinued after a positive DPT. RDD was performed in 60 patients. Of 248 initiated RDD procedures, 247 were completed. BTRs were observed in 53% of patients and 27% of RDD-procedures, with most BTRs being mild to moderate. The treatment duration was below 6 hours in 96% of RDD procedures.

Conclusion

The allergy treatment program, which included DPT and one-bag RDD-protocols, allowed patients to continue critical antineoplastic treatments despite IDHRs.

背景：在南欧和美国，快速药物脱敏（RDD）是治疗抗肿瘤药物立即药物超敏反应（IDHR）患者的基础。作为北欧第一个，丹麦对癌症患者实施了包括RDD和药物激发试验（DPT）在内的过敏治疗方案。我们报告了这种过敏干预的结果，成功治疗的数量，突破反应（BTR）的比例，时间和严重程度以及RDD程序的实际治疗持续时间。方法前瞻性观察性研究。对抗肿瘤药物过敏反应的患者纳入过敏治疗方案。对患者进行随访，直至DPT和/或RDD最终确定。按照单袋rdd方案进行rdd，药物浓度严格按照制造商的说明进行，输液器注入冲洗液。记录dpt和rdd的结果以及btr的详细信息和rdd程序的治疗时间。结果随访28个月，共纳入72例患者。对于DPT，发现了五种药物的安全替代药物，排除了六种药物的过敏，并且在DPT阳性后停止了一种治疗。60例患者行RDD。在248个启动的RDD程序中，完成了247个。在53%的患者和27%的rdd手术中观察到btr，大多数btr为轻度至中度。96%的RDD治疗持续时间低于6小时。结论过敏治疗方案包括DPT和一袋rdd方案，允许患者在IDHRs的情况下继续进行关键的抗肿瘤治疗。

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引用次数: 0

The usefulness of the basophil activation test for monitoring the effectiveness of wasp venom immunotherapy in different age groups 嗜碱性粒细胞活化试验对监测不同年龄组蜂毒免疫治疗效果的有用性

IF 4 2区医学 Q2 ALLERGY

Clinical and Translational Allergy

Pub Date : 2025-08-13 DOI: 10.1002/clt2.70073

Andrzej Bozek, Martyna Miodonska, Aleksandra Mitka, Dominika Sadowska, Janne Winterstein, Radosław Gawlik, Marita Nittner-Marszalska

To the Editor,

Allergen immunotherapy (AIT) remains a well-established and widely used approach for treating immediate type allergies including allergic rhinitis and conjunctivitis, certain forms of allergic asthma, select food allergies, and allergic reactions to Hymenoptera insect venom immunotherapy (VIT). Currently, VIT is the only causative and, in some cases, can be life-saving.¹

AIT has been proven to be effective for most age groups, including patients over 60 years old.² However, limited studies have confirmed the safety and effectiveness of VIT in these populations.² This is particularly important in cases of anaphylactic reactions following an insect sting, which is an indication for VIT also in the oldest patients.³

Therefore, evaluating of the effectiveness of VIT and the rate at which tolerance to the venom develops is of key importance. The basophil activation test (BAT) can be the optimal tool for such an evaluation. The BAT is a valuable tool for final qualification for VIT and often resolves doubts.^{4, 5} The most diagnostically valuable method for assessing the effectiveness of VIT is the live insect sting challenge (SP). However, SP has significant limitations, including the necessity of conducting it in highly specialized centers, the risk of complications, including those related to the application of the full, unfractionated dose of the allergen, and the potential risk of reactivating the allergic state. Unlike SP, the BAT for assessing VIT effectiveness is free of these limitations.⁶

The authors would like to present an assessment of the efficacy of VIT for wasp venom after 1 year of treatment in different age groups, comparing the efficacy in young and old patients to identify potential differences. This builds of an earlier observational study, which confirmed comparable efficacy after 6 months of VIT initiation in people aged 18–35 and over 60 years in the BAT test.⁷ These results were independent of the type of vaccine used Venomenhal (Hal Allergy) or Diater.

In the second part of observation, the study group was slightly reduced (drop-out due to patients' resignation despite the effectiveness of the treatment and the lack of adverse effects), and its final characteristics are presented in Table 1.

The methodology of the BAT assessment and the entire study protocol were described and consistent with the published first part of the study.⁷

The effectiveness of VIT was evaluated using BAT, revealing a statistically significant decrease in CD63 reactivity in the mean of about 86%–88% from the base for older patients similarly, as in young 84%–85% (p > 0.05) after 6 months of VIT. Similar trends were observed after next 6 months, and a comparable decrease in basophil activity was ma

致编辑，过敏原免疫疗法（AIT）仍然是一种完善和广泛使用的治疗即时型过敏的方法，包括过敏性鼻炎和结膜炎，某些形式的过敏性哮喘，特定食物过敏，以及膜翅目昆虫毒液免疫疗法（VIT）的过敏反应。目前，VIT是唯一的病因，在某些情况下，可以挽救生命。ait已被证明对大多数年龄组有效，包括60岁以上的患者然而，有限的研究已经证实了VIT在这些人群中的安全性和有效性这在昆虫叮咬后出现过敏反应的情况下尤其重要，这也是老年患者进行VIT的指征。因此，评估VIT的有效性和对毒液产生耐受性的速度是至关重要的。嗜碱性粒细胞活化试验（BAT）是进行此类评估的最佳工具。BAT是最终确定VIT资格的宝贵工具，通常可以解决疑问。4,5评估VIT有效性的最有诊断价值的方法是活体昆虫刺痛攻击（SP）。然而，SP有明显的局限性，包括必须在高度专业化的中心进行，并发症的风险，包括与应用全剂量、未分离的过敏原有关的并发症，以及重新激活过敏状态的潜在风险。与SP不同，用于评估VIT有效性的BAT没有这些限制。作者希望对VIT在不同年龄组治疗1年后对黄蜂毒液的疗效进行评估，比较年轻和老年患者的疗效，以确定潜在的差异。这建立在早期的一项观察性研究的基础上，该研究在BAT测试中证实了18-35岁和60岁以上人群在VIT启动6个月后的疗效相当这些结果与使用Venomenhal （Hal Allergy）或Diater的疫苗类型无关。在观察的第二部分，研究组的人数略有减少（治疗有效但患者退出，无不良反应），其最终特征如表1所示。描述了BAT评估的方法和整个研究方案，并与已发表的研究第一部分保持一致。使用BAT评估VIT的有效性，显示CD63反应性在老年患者中平均下降约86%-88%，在年轻患者中同样下降84%-85% (p &gt；VIT治疗6个月后0.05)。在接下来的6个月后观察到类似的趋势，并且在12个月后，嗜碱性粒细胞活性保持在相同的水平。结果如图1A-C所示。在分析6个月和12个月后的BAT结果后，没有发现年龄组或疫苗类型之间的显着差异。在整个研究组中，4.9%的患者BAT结果为阴性（不考虑面谈和阳性测试以及对蜜蜂的IgE），而3.6%的患者在VIT后与基线相比没有显着改善。得到的BAT值为暴露于1 μg/mL时的值，因为先前的数据表明，当使用标准化校准曲线时，该标准提供了灵敏度和特异性的最佳平衡。关于使用BAT监测VIT有效性的一些观察结果，但没有在老年同质组中进行。大多数作者认为BAT是一种有助于最终确定vita资格的方法。4- 6,8在开始免疫治疗后，受刺激的嗜碱性粒细胞活性显著下降，并且在治疗一年后这种趋势保持不变，这与其他作者的观察结果一致。先前的观察表明，在VIT开始后的18个月里，使用大多数亚最大浓度的昆虫毒液提取物可以减少嗜碱性粒细胞的激活。相反，在这些研究中，治疗2年后发现了较低的嗜碱性粒细胞反应性。因此，本研究将继续获得长期结果，特别是在老年患者中，以评估VIT在该组中的长期有效性。安德烈·博泽克：概念化；方法;软件;数据管理;监督;正式的分析;写作——审阅和编辑；调查。Martyna Miodonska：验证；方法;调查;软件;监督;数据管理。Aleksandra Mitka：调查；验证;可视化;项目管理;正式的分析;监督;数据管理。多米尼克·萨多夫斯卡：调查；资金收购;原创作品草案;写作——审阅和编辑；验证;正式的分析。Janne Winterstein：概念化；验证;监督;资源;数据管理;写作——审阅和编辑；融资收购。Radosław Gawlik：监督；数据管理;软件;验证;调查。 Marita Nittner-Marszalska：概念化；调查;资金收购;验证;方法;写作——审阅和编辑；项目管理;资源;监督。作者声明无利益冲突。

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引用次数: 0

Evidence of Eczematous Skin Characteristics in Mild Allergic Asthma 轻度过敏性哮喘患者皮肤湿疹特征的证据

IF 4 2区医学 Q2 ALLERGY

Clinical and Translational Allergy

Pub Date : 2025-08-06 DOI: 10.1002/clt2.70091

Anchalee Senavonge, Ruth P. Cusack, Christiane E. Whetstone, Nadia Alsaji, Karen J. Howie, Caitlin Stevens, Jennifer Wattie, Lesley Wiltshire, Roma Sehmi, Paul M. O'Byrne, Hermenio Lima, Gail M. Gauvreau

<p>To the Editor,</p><p>Atopic dermatitis (AD) and asthma are associated through common inflammatory pathways, immunologic crosstalk, barrier disruption, and genetic predisposition [<span>1</span>]. Approximately 50%–70% of asthmatic patients have AD, while 20%–40% of AD patients are diagnosed with asthma [<span>2, 3</span>]. Medications that inhibit type 2 inflammation, such as corticosteroids and dupilumab, effectively treat both conditions, suggesting an overlap in the pathogenesis of AD and asthma. Since there have been no objective skin assessments in asthmatics without a history or clinical findings of AD, we aimed to identify the proportion and characteristics of asthmatics who display skin features consistent with those of AD. The Hamilton Integrated Research Ethics Board approved this study.</p><p>Mild allergic asthmatics without a historic or current clinical findings of AD were recruited. Participants had not used any anti-inflammatory therapy for treatment of asthma, including but not limited to corticosteroids or biologics, for over 1 month before enrollment. They were characterized as asthmatic by positive methacholine challenge (PC<sub>20</sub> ≤ 16 mg/mL), and their allergic sensitization was documented through a positive skin prick test to a panel of aeroallergens. Measurements of blood total immunoglobulin E (IgE) and blood and sputum eosinophil counts were conducted. Skin biopsies of unaffected skin were obtained from the lower back using a 4 mm punch to evaluate spongiosis and vacuolization of the dermo-epidermal junction, which are characteristic findings in the skin of AD patients. Epidermal spongiosis and dermal neutrophilic and lymphocytic infiltration were measured semi-quantitatively using a 4-point scale. The severity of spongiosis was assessed as 0 (absence of haloing/vacuoles or cellular infiltrate), 1 (haloing present), 2 (haloing present with vacuoles formed), or 3 (numerous vacuoles with intravacuolar lymphocytic or neutrophilic infiltrate) [<span>4</span>]. Participants were then separated into groups based on the absence or presence of epidermal spongiosis, defined as a score of ≥ 2. Groups were compared using the independent samples <i>t</i>-test for normally-distributed data, the Mann–Whitney <i>U</i> test for non-normally distributed data, and Fisher's Exact Test for categorical data, and summary statistics are presented as mean (± SD), median (range), and number (%), respectively. The threshold for statistical significance was set at <i>p</i> < 0.05.</p><p>Fourteen asthmatic participants completed the study. The geometric mean (range) methacholine PC<sub>20</sub> was 4.5 (0.48–13.8) mg/mL, with an FEV<sub>1</sub> of 100 ± 12.7% predicted and an FEV1/FVC ratio of 0.83 ± 0.06. Allergic rhinitis was reported in 11 out of 14 (78.5%) participants. Four of the 14 participants (28.6%) had epidermal spongiosis and vacuolar infiltration consistent with eczematous skin of AD (Table 1). Low dermal lymphocyte infiltra

致编者，特应性皮炎（AD）和哮喘通过常见的炎症途径、免疫串扰、屏障破坏和遗传易感性[1]相关联。大约50%-70%的哮喘患者患有AD，而20%-40%的AD患者被诊断为哮喘[2,3]。抑制2型炎症的药物，如皮质类固醇和dupilumab，可以有效治疗这两种疾病，这表明AD和哮喘的发病机制有重叠。由于没有AD病史或临床表现的哮喘患者没有客观的皮肤评估，我们的目的是确定哮喘患者皮肤特征与AD一致的比例和特征。汉密尔顿综合研究伦理委员会批准了这项研究。招募了没有AD历史或当前临床表现的轻度过敏性哮喘患者。受试者在入组前1个月以上未使用任何抗炎疗法治疗哮喘，包括但不限于皮质类固醇或生物制剂。甲胆碱激射阳性（PC20≤16 mg/mL），表现为哮喘，并通过一组空气过敏原皮肤点刺试验阳性记录其过敏致敏性。测定血总免疫球蛋白E （IgE）和血、痰嗜酸性粒细胞计数。对未受影响的下背部皮肤进行活检，使用4mm穿孔器评估海棉病和真皮-表皮交界处的空泡化，这是AD患者皮肤的特征性表现。表皮海绵病、皮肤中性粒细胞和淋巴细胞浸润采用4分制半定量测量。海绵病的严重程度评估为0（没有晕泡/空泡或细胞浸润），1（有晕泡），2（晕泡形成）或3（大量空泡伴淋巴细胞或中性粒细胞浸润）[4]。然后根据有无表皮海绵状病（定义为评分≥2分）将参与者分为两组。组间比较对正态分布资料采用独立样本t检验，对非正态分布资料采用Mann-Whitney U检验，对分类资料采用Fisher精确检验，汇总统计量分别用均数（±SD）、中位数（极差）和数（%）表示。统计学显著性阈值设为p &lt；0.05.14名哮喘患者完成了这项研究。甲胆碱PC20几何平均值（范围）为4.5 (0.48 ~ 13.8)mg/mL， FEV1预测值为100±12.7%，FEV1/FVC比值为0.83±0.06。14名参与者中有11人（78.5%）报告了过敏性鼻炎。14名参与者中有4名（28.6%）患有与AD湿疹性皮肤一致的表皮海绵状病和空泡浸润（表1）。在非湿疹组的3名参与者中观察到低皮肤淋巴细胞浸润，并且没有活检显示中性粒细胞浸润的迹象。当比较有和没有湿疹活检的参与者时，我们发现湿疹组在活检收集时明显年龄较大（35.7±12岁对25.6±5.6岁），哮喘发作时年龄较小（6.25±2.8岁对15.8±8.3岁）。它们对室内尘螨也表现出更大的皮肤反应：翼尘螨5.5 [3.75-7.63]vs. 2 [0-3] mm尘螨，粉尘螨5.25 [3.75-6.63]vs. 1 [0-3.75] mm尘螨；p & lt;0.05)。猫、狗、马、羽毛、霉菌、双翅类、互交菌、曲霉、杂草、豚草、树木或草花粉的皮肤轮大小在两组之间相似。湿疹活检组血总IgE水平数值较高（443.5±634比261.1±397 IU/mL, p = 0.28）。两组间甲胆碱PC20、肺活量测定和痰嗜酸性粒细胞水平无差异。比较早发性哮喘和晚发性哮喘的研究揭示了不同的表型具有不同的临床特征和合并症。在早发性哮喘中，特应性合并症，如变应性鼻炎和2型炎症模式，如血清IgE和血嗜酸性粒细胞升高，更为普遍。相反，晚发性哮喘容易并发肥胖。在这个轻度过敏性哮喘人群中，我们发现AD与哮喘严重程度指数之间没有联系，如用甲基胆碱和气道嗜酸性粒细胞来测量。这可能是由于可用于活检的参与者数量有限或本研究中哮喘严重程度范围狭窄（均为轻度哮喘）。总之，目前的研究强调了本研究参与者明显的早发性哮喘表型，以及过敏性鼻炎的特应性合并症的高频率。在这种表型中，那些有皮肤湿疹病理症状的人哮喘发作的年龄明显更早。值得注意的是，在其他研究中，年龄越大，HDM暴露后皮炎症状的变化越大，这可能是由于对过敏原的致敏时间越长，因为Th2生物标志物与这两种合共病有关[2,3]。遗传易感性或免疫信号通过Th2途径可能是一个潜在的解释。在AD和哮喘中都观察到HDM致敏。螨变应原具有蛋白酶活性，可通过激活蛋白酶激活受体2 （PAR2）影响呼吸道和皮肤表皮屏障的通透性。先前的研究表明，AD的严重程度与HDM浓度有关[6,7]。此外，HDM免疫疗法在哮喘和AD中均有临床效果，表明尘螨可以通过ige介导的机制作为重要的触发因素[8,9]。需要进行更大规模的随访研究，以充分了解过敏患者皮肤和气道炎症之间的关系。本研究通过对无AD病史的哮喘患者进行皮肤活检评估，证实对屋尘螨致敏的早发性哮喘患者应密切监测其特应性皮炎的发展。写作-审查和编辑，写作-原稿，形式分析。Ruth P. Cusack：概念化、方法论、数据管理、项目管理、调查。Christiane E. wheetstone：写作-审查和编辑，形式分析，数据管理，概念化，方法论，项目管理。Nadia Alsaji：数据管理，方法论。Karen J. Howie：项目管理。凯特琳·史蒂文斯：项目管理。Jennifer Wattie：数据管理。Lesley Wiltshire：数据管理。Roma Sehmi：监督。保罗·m·奥伯恩：监督。利马：概念，调查，监督，方法论，写作-审查和编辑。Gail M. Gauvreau：概念化，方法论，数据管理，监督，写作-审查和编辑，调查，正式分析，写作-原稿。、主导者——C.E.W。,厦门市K.J.H,王秋森,成员j.w., L.W, R.S, P.M.O, G.M.G.声明没有利益冲突。H. Lima接受过咨询费用，参加过咨询委员会，并参与了以下公司的临床试验：阿斯兰制药、艾伯维（雅培）、安进、阿斯利康、鲍什健康、百时美施贵宝、新基、德美拉、礼来、葛兰素史克、Incyte、杨森、拉罗氏、利奥制药、默克夏普；Dohme、Moonlake、诺华、Pediapharma、辉瑞、RAPT、Regeneron、赛诺菲、武田和瑞银。G.M.G.已收到咨询费用，并参与以下临床试验：阿斯利康，基因泰克，第三谐波生物，蓝图医药，Biohaven, Jasper Therapeutics

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引用次数: 0

Association of ZNF608 Polymorphisms With House Dust Mite-Induced Allergic Rhinitis ZNF608基因多态性与屋尘螨致变应性鼻炎的关系

IF 4 2区医学 Q2 ALLERGY

Clinical and Translational Allergy

Pub Date : 2025-08-06 DOI: 10.1002/clt2.70081

Huiqin Li, Fang Gao, Xuyan Liu, Haoran Shen, Mulong Du, Lei Cheng, Huihui Zhang, Zhengdong Zhang, Meiping Lu, Rui Zheng

Background

Genetic factors contribute essentially to the pathophysiology of house dust mite (HDM)-induced allergic rhinitis. Previous studies mainly focused on the biological pathogenesis, but the heritability remains poorly explained.

Methods

A genome-wide gene association analysis (GWGAS) integrating joint-genetic variant effects at the gene level was initially conducted on allergic rhinitis, validated by differential gene expression analysis. A weighted polygenic risk score (wPRS) was used to proxy the cumulative effect of candidate genetic variants in key genes. Gene-set analysis and eQTL analysis were performed to explore the immunologic pathway and genetic regulation of the key gene.

Results

ZNF608 was identified as the key gene involving HDM-induced allergic rhinitis risk (p = 1.23 × 10⁻⁶), which was highly expressed in nasal epithelium cells of allergic rhinitis patients (p = 0.041). Furthermore, a wPRS of five significant variants, rs6862252, rs10067299, rs10042766, rs6866116, and rs79679768 in the ZNF608, showed the cumulative effect was associated with the increased HDM-induced allergic rhinitis risk (odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.18–1.65, p = 1.18 × 10⁻⁴), with varied effects under diverse conditions of nasal symptoms. Additionally, both rs6862252 G allele and rs10042766 T allele elevated the expression of ZNF608 involving in state and perturbation of immune cells, such as B cell, T cell, and dendritic cell, contributing to HDM-induced allergic rhinitis.

Conclusion

This study highlights the key gene ZNF608 of HDM-induced allergic rhinitis, which may lay the groundwork for risk assessment and early diagnosis of allergic rhinitis.

遗传因素对屋尘螨（HDM）诱发的变应性鼻炎的病理生理起重要作用。以往的研究主要集中在生物学发病机制上，但对其遗传能力的解释仍然很差。方法首先对变应性鼻炎进行基因水平联合遗传变异效应的全基因组基因关联分析（GWGAS），并通过差异基因表达分析进行验证。使用加权多基因风险评分（wPRS）来代表关键基因候选遗传变异的累积效应。通过基因集分析和eQTL分析，探讨关键基因的免疫途径和遗传调控。结果ZNF608被鉴定为hdm诱导变应性鼻炎风险的关键基因（p = 1.23 × 10−6），在变应性鼻炎患者鼻上皮细胞中高表达（p = 0.041）。此外，ZNF608中5个显著变异rs6862252、rs10067299、rs10042766、rs6866116和rs79679768的wPRS显示，累积效应与hdm诱导的变应性鼻炎风险增加相关（优势比[OR] = 1.40, 95%可信区间[CI] = 1.18 - 1.65, p = 1.18 × 10−4），且在不同的鼻腔症状条件下影响不同。此外，rs6862252 G等位基因和rs10042766 T等位基因均升高ZNF608的表达，参与免疫细胞（如B细胞、T细胞、树突状细胞）的状态和扰动，参与hdm诱导的变应性鼻炎。结论本研究明确了hdm致变应性鼻炎的关键基因ZNF608，为变应性鼻炎的风险评估和早期诊断奠定了基础。

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引用次数: 0

Genetic and Environmental Contributions to Serological Biomarkers of Extracellular Matrix Remodeling in Asthma: A Twin Study 遗传和环境对哮喘患者细胞外基质重塑的血清学生物标志物的影响：一项双胞胎研究

IF 4 2区医学 Q2 ALLERGY

Clinical and Translational Allergy

Pub Date : 2025-08-04 DOI: 10.1002/clt2.70089

Matej Andelic, Vibeke Backer, Kirsten Ohm Kyvik, Signe Holm Nielsen, Simon Francis Thomsen

Background

Asthma is characterized by airway obstruction driven by chronic inflammation, leading to extracellular matrix (ECM) remodeling. This involves ECM alterations, including increased collagen deposition and elastolysis, resulting in airway wall thickening and irreversible airflow limitation. Despite ECM remodeling's known role in asthma, no reliable tools track these changes, and the genetic and environmental factors driving them remain unclear.

Objective

This study investigated ECM remodeling in asthma by assessing 12 serological neo-epitopes related to collagen synthesis, degradation, and immune cell activity. Studying monozygotic (MZ) and dizygotic (DZ) twins, we explored genetic and environmental influences on ECM changes.

Methods

The study included 512 individuals from 256 twin pairs (89 MZ, 167 DZ), of which 200 were healthy and 312 had asthma. An exploratory panel of 12 ECM biomarkers reflecting type III and VI collagen formation (PRO-C3, PRO-C6), turnover (PRO-C4), degradation (C3M, C4M, C4Mα3, C6M, C7M), and immune cell activity (VICM, ELP-3, ELA-HNE, CC16-HNE) was measured in serum using ELISA.

Results

Asthma was linked to increased type IV collagen degradation (C4M). Airway obstruction showed decreased PRO-C6, C4Mα3, C6M, and C7M, while C4M and ELP-3 were elevated among twins. Classical twin analyses revealed genetic influence on multiple biomarkers, primarily C4Mα3, C7M, CC16-HNE, and VICM.

Conclusion

This study highlights ECM remodeling's role in asthma and airway obstruction, identifying distinct biomarker profiles. Genetic factors significantly influence ECM changes, suggesting potential genetic predispositions for ECM alterations and offering insights into asthma pathogenesis and future diagnostic and therapeutic strategies.

哮喘的特征是由慢性炎症引起的气道阻塞，导致细胞外基质（ECM）重塑。这涉及到ECM的改变，包括胶原沉积和弹性溶解增加，导致气道壁增厚和不可逆的气流限制。尽管已知ECM重塑在哮喘中的作用，但没有可靠的工具跟踪这些变化，并且驱动它们的遗传和环境因素仍不清楚。目的通过评估与胶原合成、降解和免疫细胞活性相关的12个血清学新表位，探讨哮喘中ECM的重塑。研究单卵双胞胎（MZ）和异卵双胞胎（DZ），我们探讨了遗传和环境对ECM变化的影响。方法对256对双胞胎（MZ 89对，DZ 167对）中的512人进行研究，其中健康200人，哮喘312人。采用ELISA法检测血清中反映III型和VI型胶原形成（PRO-C3、PRO-C6）、转化（PRO-C4）、降解（C3M、C4M、C4Mα3、C6M、C7M）和免疫细胞活性（VICM、ELP-3、ELA-HNE、CC16-HNE）的12种ECM生物标志物。结果哮喘与IV型胶原降解（C4M）增加有关。双胞胎气道阻塞表现为PRO-C6、C4Mα3、C6M、C7M降低，C4M、ELP-3升高。经典双生子分析揭示了遗传对多种生物标志物的影响，主要是C4Mα3、C7M、CC16-HNE和VICM。结论本研究强调了ECM重塑在哮喘和气道阻塞中的作用，确定了不同的生物标志物谱。遗传因素显著影响ECM改变，提示ECM改变的潜在遗传易感性，并为哮喘发病机制和未来的诊断和治疗策略提供见解。

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引用次数: 0

Lung Acetate Levels Decline in Correlation With Increased Type 2 Allergic Markers in a House Dust Mite Allergic Mouse Model 屋尘螨过敏小鼠模型中肺醋酸盐水平下降与2型过敏标志物升高相关

IF 4 2区医学 Q2 ALLERGY

Clinical and Translational Allergy

Pub Date : 2025-08-04 DOI: 10.1002/clt2.70082

Roos E. M. Verstegen, Rolf W. Sparidans, Atanaska I. Kostadinova, Johan Garssen, Gert Folkerts, Rudi W. Hendriks, Linette E. M. Willemsen

Aims

Microbial dysbiosis is an important feature in allergic asthma. Short-chain fatty acids (SCFA) produced by the intestinal microbiome play a role in the gut-lung axis. Little is known about how the gut SCFA levels reflect SCFA levels in other tissues and how these link to the allergic asthma inflammatory status.

Materials and Methods

Male BALB/c mice were intranasally exposed to house dust mite (HDM) to induce allergic airway inflammation. Acetate, propionate, and butyrate levels were determined in caecum content, serum and lungs of control and HDM-allergic mice using liquid chromatography-mass spectrometry. Faecal microbiome composition was determined by DNA sequencing.

Results

Mean acetate:propionate:butyrate ratios were 75:15:10 in caecum content, 98:1.5:0.5 in serum, and 38:61:1 in the lung. SCFA levels did not correlate across compartments and propionate was relatively high in the lungs. The faecal microbiome of allergic mice differed from control, with increased Desulfovibrionaceae abundance. The lung acetate proportion was lower in allergic mice compared to control. In allergic mice, declining lung acetate levels correlated with increased HDM-specific IgE in serum and IL-13 release by ex vivo HDM-restimulated lung cells. Ex vivo acetate supplementation did not inhibit HDM-restimulated lung cell IL-13 production, while butyrate and propionate did.

Conclusions

Overall, HDM-driven murine allergic airway inflammation induced changes in the faecal microbiome and reduced acetate in serum and lung tissue. Hereby, lung acetate levels correlated negatively with sensitisation and type-2 inflammation, but acetate itself did not suppress ex vivo HDM-induced cytokine release. Our findings provide new insights on the systemic effects of HDM-allergic inflammation along the gut-lung axis.

目的微生物生态失调是过敏性哮喘的重要特征。肠道微生物组产生的短链脂肪酸（SCFA）在肠-肺轴中发挥作用。关于肠道SCFA水平如何反映其他组织中的SCFA水平以及这些与过敏性哮喘炎症状态的关系，我们知之甚少。材料与方法将雄性BALB/c小鼠经鼻暴露于屋尘螨（HDM）诱导变应性气道炎症。采用液相色谱-质谱法测定对照组和hdm过敏小鼠的盲肠内容物、血清和肺中的乙酸、丙酸和丁酸水平。通过DNA测序测定粪便微生物组组成。结果盲肠中乙酸：丙酸：丁酸的平均比值为75:15:10，血清中为98:1.5:0.5，肺中为38:61:1。SCFA水平在肺间室之间没有相关性，丙酸在肺中相对较高。过敏小鼠的粪便微生物群与对照组不同，有增加的Desulfovibrionaceae丰度。与对照组相比，过敏小鼠肺中醋酸盐比例较低。在过敏小鼠中，肺醋酸盐水平的下降与血清中hdm特异性IgE和体外hdm再刺激肺细胞释放IL-13的增加相关。体外补充醋酸盐不会抑制hdm刺激的肺细胞IL-13的产生，而丁酸盐和丙酸盐则会。总体而言，hdm驱动的小鼠过敏性气道炎症诱导了粪便微生物组的变化以及血清和肺组织中醋酸盐的减少。因此，肺醋酸盐水平与致敏和2型炎症呈负相关，但醋酸盐本身并不抑制体外hdm诱导的细胞因子释放。我们的研究结果为hdm过敏性炎症沿肠-肺轴的全身影响提供了新的见解。

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引用次数: 0