Annals of Allergy Asthma & Immunology最新文献_第9页

Disclosures 披露的信息

IF 4.7 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2025-11-01 DOI: 10.1016/S1081-1206(25)01296-7

引用次数: 0

HOME EGG LADDER INITIATION IN CHILDREN WITH ISOLATED CUTANEOUS SYMPTOMS FOLLOWING EGG EXPOSURE 接触鸡蛋后出现孤立皮肤症状的儿童的家庭鸡蛋阶梯启动

IF 4.7 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2025-11-01 DOI: 10.1016/j.anai.2025.08.029

S. Pawer , N. Yu , S. Jeimy , S. Erdle , T. Wong , V. Cook

Introduction

Referrals for cutaneous symptoms following egg exposure are commonly received by pediatric allergists. At our community allergy clinic, 47% of food allergy referrals for 0–2-year-olds involve egg. Rather than traditional egg avoidance, the Canadian Egg Ladder facilitates reintroduction. We describe home egg ladder initiation in patients with cutaneous symptoms, to assess safety and potential to decrease allergist assessments.

Methods

From 2018–2025, 0–2-year-olds with isolated cutaneous symptoms began the egg ladder at home, without in-person allergist assessment. Caregivers were educated on initiation, and epinephrine autoinjectors were prescribed. Patients were reviewed every 3–6 months. Demographics, adverse reactions, and ladder progress were recorded. Descriptive statistics were analyzed in Excel. As quality improvement, this study was exempted from IRB approval.

Results

Of 116 patients who began the egg ladder, 84% (n=97) completed it. Median initiation age was 12 months (IQR 9–16); average completion time was 6 months (IQR 2–9). Twenty-five patients (22%) experienced adverse reactions, predominantly contact rashes (18/25; 72%). Six experienced grade 1 CoFAR reactions, two experienced grade 2 CoFAR reactions. No patients required epinephrine. Attrition rate was 8%; 7% transitioned to oral immunotherapy (5 ladder failure, 2 parental anxiety, 1 logistical burden). Based on egg tolerance by time of allergy assessment, ladder initiation by referring providers could have prevented 63% of allergy referrals.

Conclusion

This study supports safe, effective home initiation of the egg ladder for pediatric patients with isolated cutaneous symptoms after egg exposure. Implementing ladders in primary care may reduce unnecessary allergist referrals, shortening wait times and improving access for those requiring specialist care.

介绍：儿童过敏专科医生通常会收到接触鸡蛋后皮肤症状的转诊。在我们的社区过敏诊所，0 - 2岁儿童的食物过敏转诊中有47%涉及鸡蛋。而不是传统的鸡蛋避免，加拿大鸡蛋梯子促进重新引入。我们描述了家庭鸡蛋阶梯在皮肤症状患者中的启动，以评估安全性和减少过敏医师评估的潜力。方法2018-2025年，0 - 2岁的儿童在没有过敏专家评估的情况下，在家中开始鸡蛋阶梯治疗。护理人员接受了启蒙教育，并开了肾上腺素自身注射器。每3-6个月复查一次。记录人口统计、不良反应和阶梯进展。在Excel中进行描述性统计分析。作为质量改进，本研究免IRB审批。结果116例开始卵梯的患者中，84% （n=97）完成了卵梯。起始年龄中位数为12个月（IQR 9-16）；平均完成时间为6个月（IQR 2-9）。25例患者（22%）出现不良反应，主要是接触性皮疹（18/25;72%）。6例发生1级CoFAR反应，2例发生2级CoFAR反应。没有病人需要肾上腺素。流失率为8%；7%转为口服免疫治疗（阶梯失败5例，父母焦虑2例，后勤负担1例）。根据过敏评估时间的鸡蛋耐受性，转诊提供者的阶梯启动可以阻止63%的过敏转诊。结论：本研究支持对暴露于鸡蛋后出现孤立皮肤症状的儿科患者进行安全有效的家庭鸡蛋阶梯治疗。在初级保健中实施阶梯可减少不必要的过敏症专家转诊，缩短等待时间，并改善需要专科护理的患者的可及性。

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引用次数: 0

UTILITY OF NEUTROPHIL-TO-LYMPHOCYTE RATIO IN PATIENTS WITH DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS) 中性粒细胞/淋巴细胞比值在伴嗜酸性粒细胞增多和全身症状的药物反应患者中的应用（dress）

IF 4.7 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2025-11-01 DOI: 10.1016/j.anai.2025.08.056

P. Pureesrisak , V. Jaroenpuntaruk , D. Voelker , A. Alavi , S. Chiarella , T. Pongdee

Introduction

DRESS is a severe cutaneous adverse drug reaction associated with significant morbidity. Blood neutrophil-to-lymphocyte ratio (NLR) has shown prognostic potential in other drug reactions but remains understudied in DRESS.

Methods

We performed a retrospective study of patients diagnosed with DRESS at our institution from 2015–2024. Extracted data included demographics, culprit drugs, laboratory parameters, and clinical course.

Results

Among 126 patients, the mean age was 55.4 years (SD=19.7; range 1-99), and 60.3% were female. Fever was present in 68.3% of patients, and mucosal involvement occurred in 15.1%. Internal organ involvement occurred in 92.1% with the liver being the most common organ involved (82%). Rash morphology was morbilliform in 88.9%, with additional patterns including exfoliative dermatitis (10.3%), vesiculobullous lesions (4%), purpuric rash (6.3%), target-like lesions (3.2%), and pustular eruption (3.2%).

Mean RegiSCAR score was 5.5 (SD=1.18), and the most common culprit drugs included vancomycin, trimethoprim-sulfamethoxazole, and lamotrigine. The mean duration of DRESS was 30.1 days (SD=27.1, 95% CI [25.3, 35]). Mean NLR at presentation was 7.51 (SD=12.9, 95% CI [5.22, 9.79]). NLR did not correlate with age, and there was no significant difference in mean NLR between males and females. The mean NLR for hospitalized patients was significantly higher than those not hospitalized (7.82 vs. 3.51, p=0.0021). In females, NLR significantly correlated with peak ALT (p=0.0064), peak ALP (p=0.0152), and peak serum creatinine (p=0.0434).

Conclusion

Greater NLR may be associated with higher rates of hospitalization as well as liver and kidney involvement, highlighting its potential role in early severity DRESS assessment.

dress是一种严重的皮肤药物不良反应，发病率高。血液中性粒细胞与淋巴细胞比率（NLR）在其他药物反应中显示出预后潜力，但在DRESS中仍未得到充分研究。方法对2015-2024年在我院诊断为DRESS的患者进行回顾性研究。提取的数据包括人口统计、罪魁祸首药物、实验室参数和临床病程。结果126例患者平均年龄55.4岁（SD=19.7，范围1 ~ 99），女性占60.3%。68.3%的患者出现发热，15.1%的患者出现黏膜受累。92.1%发生内脏受累，其中肝脏是最常见的受累器官（82%）。皮疹形态为麻疹型，占88.9%，其他类型包括剥脱性皮炎（10.3%）、水泡性病变（4%）、紫癜性皮疹（6.3%）、靶样性病变（3.2%）和脓疱性皮疹（3.2%）。RegiSCAR平均评分为5.5 (SD=1.18)，最常见的罪魁祸首药物包括万古霉素、甲氧苄啶-磺胺甲恶唑和拉莫三嗪。DRESS的平均持续时间为30.1天（SD=27.1, 95% CI[25.3, 35]）。就诊时的平均NLR为7.51 （SD=12.9, 95% CI[5.22, 9.79]）。NLR与年龄无关，男女平均NLR无显著差异。住院患者的平均NLR显著高于未住院患者（7.82 vs. 3.51, p=0.0021）。在女性中，NLR与ALT峰值（p=0.0064）、ALP峰值（p=0.0152）和血清肌酐峰值（p=0.0434）显著相关。结论NLR越大，住院率越高，肝脏和肾脏受累率也越高，这在早期严重程度DRESS评估中具有潜在作用。

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引用次数: 0

DIAGNOSIS OF CLONAL MAST CELL DISEASE IN PATIENTS WITH ANAPHYLAXIS 过敏性反应患者克隆肥大细胞病的诊断

IF 4.7 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2025-11-01 DOI: 10.1016/j.anai.2025.08.033

I. Alvarez-Twose , M. Jara-Acevedo , B. Poladura , R. Sandoval-Arroyo , B. Lampson , D. Shaheen , A. Orfao

Introduction

Clonal mast cell (MC) diseases (cMCD), including systemic mastocytosis, are a group of conditions frequently driven in adults by the KIT D816V mutation. The PROSPECTOR study (NCT04811365) reported 4% prevalence of KIT D816V mutation in peripheral blood (PB) of patients with anaphylaxis or severe symptoms of MC activation using droplet digital PCR (ddPCR). However, the prevalence of both KIT D816V and cMCD in this population may be higher. The objective of this study is to measure the prevalence of cMCD and KIT D816V in a subset of patients presenting with anaphylaxis at a single PROSPECTOR study site.

Methods

Testing for KIT D816V in PB by ddPCR and allele-specific oligonucleotide quantitative PCR (ASO-qPCR) and calculation of the Spanish Network on Mastocytosis score (REMA, predictive tool; score ≥2 suggests high probability of cMCD) were performed for all patients. A subset of 40/57 patients was assessed for cMCD leveraging a bone marrow (BM) biopsy.

Results

Data from 57 patients were analyzed. A total of 29/57 (51%) patients were diagnosed with cMCD (22 with BM mastocytosis [BMM] and 7 with monoclonal MC activation syndrome [MMAS]). All patients with BMM and 1/7 patients with MMAS had detectable KIT D816V mutation. Sensitivity for detecting cMCD was 10% with ddPCR, 34% with ASO-qPCR, and 83% with the REMA score.

Conclusion

The prevalence of cMCD is enriched in patients with anaphylaxis. Lack of detectable KIT D816V in PB should not bar further testing in patients with a presentation suggestive of cMCD, such as a REMA score ≥2.

克隆肥大细胞（MC）疾病（cMCD），包括全身性肥大细胞增多症，是一组经常由KIT D816V突变驱动的成人疾病。PROSPECTOR研究（NCT04811365）使用液滴数字PCR （ddPCR）报告了过敏反应或MC激活严重症状患者外周血（PB）中KIT D816V突变的患病率为4%。然而，KIT D816V和cMCD在这一人群中的患病率可能更高。本研究的目的是在一个单一的PROSPECTOR研究地点测量出现过敏反应的患者亚群中cMCD和KIT D816V的患病率。方法采用ddPCR和等位基因特异性寡核苷酸定量PCR （ASO-qPCR）检测PB中KIT D816V，计算西班牙肥大细胞增多症网络评分（REMA，预测工具，评分≥2提示cMCD的高概率）。通过骨髓活检评估40/57例患者的cMCD。结果分析了57例患者的资料。共有29/57（51%）的患者被诊断为cMCD（22例为BM肥大细胞增多症[BMM]， 7例为单克隆MC激活综合征[MMAS]）。所有BMM患者和1/7 MMAS患者均可检测到KIT D816V突变。ddPCR检测cMCD的灵敏度为10%，ASO-qPCR为34%，REMA评分为83%。结论cMCD在过敏反应患者中患病率较高。对于有cMCD表现的患者（如REMA评分≥2），PB中缺乏可检测的KIT D816V不应妨碍进一步检测。

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引用次数: 0

LONG-TERM SAFETY AND EFFICACY OF ORAL DEUCRICTIBANT FOR TREATMENT OF HEREDITARY ANGIOEDEMA ATTACKS: RAPIDE-2 RESULTS 口服减湿剂治疗遗传性血管性水肿发作的长期安全性和有效性：快速2结果

IF 4.7 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2025-11-01 DOI: 10.1016/j.anai.2025.08.106

J. Anderson , E. Aygoren-Pursun , H. Farkas , J. Jacobs , M. Manning , A. Valerieva , G. Giannattasio , Y. Li , M. Yu , M. Riedl

Introduction

Hereditary angioedema (HAE) attacks are caused by excess bradykinin activating bradykinin B2 receptors. Deucrictibant is a selective, orally administered bradykinin B2 receptor antagonist under development for prophylactic and on-demand treatment (ODT) of HAE attacks.

Methods

RAPIDe-2 (NCT05396105) is a two-part, Phase 2/3 extension study evaluating long-term safety and efficacy of deucrictibant immediate-release (IR) capsule for ODT of successive HAE attacks. RAPIDe-2 Part A enrolled adult participants who completed the Phase 2 RAPIDe-1 placebo-controlled trial. Participants self-administered the same double-blinded RAPIDe-1 dose of deucrictibant (10mg/20mg/30mg) to treat qualifying HAE attacks.

Results

Final RAPIDe-2 part A data included 465 attacks treated with deucrictibant by 19 participants. Deucrictibant IR capsule was generally well tolerated, with no treatment-related treatment emergent adverse events. Measured using Patient Global Impression of Change (PGI-C), the median (95% confidence intervals [CIs]) time to onset of symptom relief and to substantial symptom relief was 1.1 (1.0–1.1) and 2.5 (2.1–2.9) hours, respectively. Onset of and substantial symptom relief were achieved by 12 hours in 97.8% and 95.2% of attacks, respectively. Measured using PGI-Severity (PGI-S), the median time to reduction in attack severity and to complete attack resolution was 2.8 (2.3, 2.9) and 10.6 (8.5–11.5) hours, respectively. The latter was achieved at 24 hours by 86.9% of attacks. Overall, 85.4% of attacks were treated with a single dose of deucrictibant.

Conclusion

Final results from RAPIDe-2 part A extension study provide further evidence on long-term safety and efficacy of deucrictibant IR capsule for ODT of HAE attacks.

遗传性血管性水肿（HAE）发作是由过量的缓激肽激活缓激肽B2受体引起的。Deucrictibant是一种选择性口服缓激肽B2受体拮抗剂，正在开发用于HAE发作的预防性和按需治疗（ODT）。方法rapide -2 （NCT05396105）是一项2部分2/3期扩展研究，评估脱硝剂速释（IR）胶囊用于连续HAE发作的ODT的长期安全性和有效性。RAPIDe-2 A部分招募完成2期RAPIDe-1安慰剂对照试验的成人受试者。参与者自行给予相同双盲RAPIDe-1剂量的脱硝剂（10mg/20mg/30mg）来治疗符合条件的HAE发作。结果RAPIDe-2 A部分最终数据包括19名参与者使用除湿剂治疗的465次攻击。Deucrictibant IR胶囊一般耐受性良好，无治疗相关的紧急不良事件。使用患者总体变化印象（PGI-C）测量，到症状缓解和实质性症状缓解的中位时间（95%置信区间[ci]）分别为1.1（1.0-1.1）和2.5（2.1-2.9）小时。97.8%的发作和95.2%的发作在12小时内实现发作和实质性症状缓解。使用PGI-Severity （PGI-S）测量，攻击严重程度降低和完全攻击解决的中位时间分别为2.8（2.3,2.9）和10.6（8.5-11.5）小时。后者在24小时内实现了86.9%的攻击。总的来说，85.4%的发作用单剂脱氧剂治疗。RAPIDe-2 A部分扩展研究的最终结果进一步证明了脱硝剂IR胶囊治疗HAE发作ODT的长期安全性和有效性。

{"title":"LONG-TERM SAFETY AND EFFICACY OF ORAL DEUCRICTIBANT FOR TREATMENT OF HEREDITARY ANGIOEDEMA ATTACKS: RAPIDE-2 RESULTS","authors":"J. Anderson , E. Aygoren-Pursun , H. Farkas , J. Jacobs , M. Manning , A. Valerieva , G. Giannattasio , Y. Li , M. Yu , M. Riedl","doi":"10.1016/j.anai.2025.08.106","DOIUrl":"10.1016/j.anai.2025.08.106","url":null,"abstract":"<div><h3>Introduction</h3><div>Hereditary angioedema (HAE) attacks are caused by excess bradykinin activating bradykinin B2 receptors. Deucrictibant is a selective, orally administered bradykinin B2 receptor antagonist under development for prophylactic and on-demand treatment (ODT) of HAE attacks.</div></div><div><h3>Methods</h3><div>RAPIDe-2 (NCT05396105) is a two-part, Phase 2/3 extension study evaluating long-term safety and efficacy of deucrictibant immediate-release (IR) capsule for ODT of successive HAE attacks. RAPIDe-2 Part A enrolled adult participants who completed the Phase 2 RAPIDe-1 placebo-controlled trial. Participants self-administered the same double-blinded RAPIDe-1 dose of deucrictibant (10mg/20mg/30mg) to treat qualifying HAE attacks.</div></div><div><h3>Results</h3><div>Final RAPIDe-2 part A data included 465 attacks treated with deucrictibant by 19 participants. Deucrictibant IR capsule was generally well tolerated, with no treatment-related treatment emergent adverse events. Measured using Patient Global Impression of Change (PGI-C), the median (95% confidence intervals [CIs]) time to onset of symptom relief and to substantial symptom relief was 1.1 (1.0–1.1) and 2.5 (2.1–2.9) hours, respectively. Onset of and substantial symptom relief were achieved by 12 hours in 97.8% and 95.2% of attacks, respectively. Measured using PGI-Severity (PGI-S), the median time to reduction in attack severity and to complete attack resolution was 2.8 (2.3, 2.9) and 10.6 (8.5–11.5) hours, respectively. The latter was achieved at 24 hours by 86.9% of attacks. Overall, 85.4% of attacks were treated with a single dose of deucrictibant.</div></div><div><h3>Conclusion</h3><div>Final results from RAPIDe-2 part A extension study provide further evidence on long-term safety and efficacy of deucrictibant IR capsule for ODT of HAE attacks.</div></div>","PeriodicalId":50773,"journal":{"name":"Annals of Allergy Asthma & Immunology","volume":"135 5","pages":"Pages S31-S32"},"PeriodicalIF":4.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145442492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

EFFICACY OF INTRANASAL EPINEPHRINE FOR THE TREATMENT OF ANAPHYLAXIS FOLLOWING SUBCUTANEOUS ALLERGY IMMUNOTHERAPY 鼻内肾上腺素治疗皮下过敏免疫治疗后过敏反应的疗效

IF 4.7 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2025-11-01 DOI: 10.1016/j.anai.2025.08.062

P. Ogershok, T. Ogershok

Introduction

Allergy immunotherapy effectively reduces symptoms in atopic patients but carries a risk of anaphylaxis, a rare but serious complication. This case series investigates the use of intranasal epinephrine as an alternative treatment in an outpatient setting.

Methods

Patients who experienced anaphylaxis following allergy immunotherapy from October 1, 2024 to June 15, 2025, were included. Demographic data and clinical episodes where collected through chart reviews from an allergy clinic.

Results

Six anaphylactic episodes were reported among patients aged 15 to 46, including one pediatric patient. The cohort consisted of four males and two females, with only the pediatric patient having a history of asthma. Reactions occurred within 20 minutes for three patients and after 30 minutes for the remaining three, all within 90 minutes of immunotherapy injection. Symptoms included facial flushing, itchy skin, cough, shortness of breath, nasal congestion, and rhinorrhea. Intranasal epinephrine was administered within one minute of identifying the reaction or when the patient returned to the clinic for the late reactions. All patients showed significant clinical improvement in symptoms within 2 to 7 minutes post administration. Side effects were minimal, with one case of nasal burning and another of nasal tingling sensation. No patients required a second dose of intranasal epinephrine.

Conclusion

This case series demonstrates that intranasal epinephrine is an effective treatment for anaphylaxis following subcutaneous allergy immunotherapy injections in an outpatient setting, offering a promising alternative to traditional intramuscular administration.

Demographics of patients requiring intranasal epinephrine after anaphylaxis

过敏免疫疗法可有效减轻特应性患者的症状，但有发生过敏反应的风险，这是一种罕见但严重的并发症。本病例系列调查使用鼻内肾上腺素作为一种替代治疗在门诊设置。方法纳入2024年10月1日至2025年6月15日接受过敏免疫治疗后发生过敏反应的患者。人口统计数据和临床发作是通过过敏诊所的图表审查收集的。结果6例15 ~ 46岁患者发生过敏反应，其中1例为儿科患者。该队列包括4名男性和2名女性，只有儿科患者有哮喘史。3例患者在20分钟内发生反应，其余3例在30分钟后发生反应，均在免疫治疗注射后90分钟内发生反应。症状包括面部潮红、皮肤瘙痒、咳嗽、呼吸急促、鼻塞和鼻漏。鼻内肾上腺素是在一分钟内确定的反应或当病人返回诊所的晚期反应给予。所有患者在给药后2 ~ 7分钟临床症状均有明显改善。副作用最小，1例鼻灼烧，1例鼻刺痛感。没有患者需要第二剂鼻内肾上腺素。结论：本病例系列表明，鼻内肾上腺素是一种有效的治疗过敏反应后皮下过敏免疫治疗注射在门诊设置，提供了一个有希望的替代传统的肌肉注射给药。过敏反应后需要鼻内肾上腺素的患者的人口统计学

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引用次数: 0

PRECLINICAL EVALUATION OF A MRGX2 TARGETING CYTAC FOR DEPLETING TISSUE-RESIDENT MAST CELLS 8224 mrgx2靶向cytac消耗组织常驻肥大细胞的临床前评估

IF 4.7 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2025-11-01 DOI: 10.1016/j.anai.2025.08.078

J. Duvall, J. O'Neil, S. Wiltzius, M. Baptista, C. Leach, B. Turunen

Introduction

Mast cells have been identified as playing a key role in several allergic diseases. The MAS-related G protein-coupled receptor, MRGX2, is uniquely expressed on tissue-resident mast cells. We developed a MRGX2 Cytotoxicity Targeting Chimera (CyTAC^TM) that is designed to potently and selectively bind MRGX2 on mast cells. When the MRGX2-CyTAC is combined with the antibody-dependent cell-mediated cytotoxicity (ADCC) platform antibody, target mast cells are eliminated via enhanced effector mediated killing.

Results

ADCC was assessed using a reporter assay with a MRGX2-transduced HEK293 cell line. Mast cell killing was evaluated using LAD2 cells or human CD34-derived mast cells in the presence of NK cells or in a human skin explant. In vivo studies were performed in wildtype or knock-in human MRGX2 expressing mice.

Chemistry optimization led to the identification of a potent and selective MRGX2 CyTAC with low nM potency as assessed in an ADCC reporter assay. The MRGX2 CyTAC was able to effectively kill mast cells when co-cultured with NK cells in a target-dependent and dose dependent fashion. No mast cell killing was observed when using the CyTAC alone or antibody alone. Similarly, depletion of CD45+ CD117+ cells was demonstrated in a human skin explant. In vivo studies demonstrated that, in the presence of the ADCC platform antibody, the MRGX2 CyTAC takes on the PK characteristics of the antibody, allowing for infrequent dosing.

Conclusion

We have developed a MRGX2-targeting CyTAC which is able to effectively and dose-dependently deplete disease driving mast cells expressed in the skin.

肥大细胞已被确定在几种过敏性疾病中起关键作用。mas相关的G蛋白偶联受体MRGX2在组织驻留肥大细胞上唯一表达。我们开发了一种MRGX2细胞毒性靶向嵌合体（CyTACTM），旨在有效和选择性地将MRGX2结合在肥大细胞上。当MRGX2-CyTAC与抗体依赖细胞介导的细胞毒性（ADCC）平台抗体联合使用时，靶肥大细胞通过增强的效应介导杀伤被消除。结果使用mrgx2转导的HEK293细胞系进行报告细胞试验评估adcc。使用LAD2细胞或人cd34来源的肥大细胞在NK细胞存在或人皮肤外植体中评估肥大细胞杀伤作用。体内研究在野生型或敲入型表达MRGX2的小鼠中进行。化学优化导致鉴定出一种有效的、选择性的MRGX2 CyTAC，并在ADCC报告分析中评估了其低nM效价。当MRGX2 CyTAC与NK细胞以靶依赖和剂量依赖的方式共培养时，能够有效杀死肥大细胞。单独使用CyTAC或单独使用抗体时，未观察到肥大细胞杀伤。类似地，CD45+ CD117+细胞在人皮肤外植体中被证明是耗尽的。体内研究表明，在ADCC平台抗体存在下，MRGX2 CyTAC具有抗体的PK特性，允许不频繁给药。结论：我们开发了一种靶向mrgx2的CyTAC，能够有效且剂量依赖性地消耗皮肤中表达的疾病驱动肥大细胞。

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引用次数: 0

PRACTICAL EVALUATION OF BIOLOGIC HYPERSENSITIVITY IN A DRUG ALLERGY CLINIC: A 10-YEAR REVIEW 药物过敏临床生物超敏反应的实际评价：10年回顾

IF 4.7 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2025-11-01 DOI: 10.1016/j.anai.2025.08.020

T. Ratchataswan , R. Lee , M. Krantz , G. Koo , E. Phillips , C. Stone

Introduction

Biologic agents are increasingly used in clinical practice and may cause diverse adverse reactions. However, clear guidance on evaluating and managing these reactions remains limited.

Methods

We reviewed the drug allergy clinic’s REDCap database for all cases of an allergy label to biologics that were evaluated between May 2014 to April 2024. Sixty-two labels of biologic reaction from 57 unique patients (5 with two labels) were included. Chart reviews assessed demographics, reaction history, testing, and treatment recommendations.

Results

Twenty-three unique biologics were implicated (Table), most commonly Ustekinumab (10, 16.1%), Evolocumab (7, 11.3%), and Infliximab (6, 9.7%). Anaphylaxis occurred in 9 cases (14.5%) and other acute IgE-type symptoms in 5 (8.1%). Non-IgE-mediated reactions were most frequent (28, 45.2%) and included delayed urticaria/angioedema (25.0%), nonspecific rash (28.6%), local reactions (21.4%), neuropathy (10.7%), flu-like symptoms (7.1%), nasal itching (3.6%), and lightheadedness (3.6%). Severe cutaneous adverse reactions occurred in 2 cases (3.2%), and infusion reactions in 10 (16.1%). Testing was done in 25 cases (40.3%), including 20 skin tests (18 to excipients, 2 to the biologic), all negative except one positive for methylprednisolone acetate. Two patients underwent successful drug challenges. Recommendations included premedication (33.9%), continued use (25.8%), desensitization (8.1%), avoidance (16.1%), switching to another biologic with the same excipient (9.7%), or within class (6.5%).

Conclusion

Most reactions to biologics were non-IgE-mediated when evaluated, highlighting the importance of clinical history in evaluation. Most hypersensitivity to biologics seems unlikely to be excipient-related. Premedication, modified use, and alternative biologics can be effectively identified to ensure continued treatment.

生物制剂越来越多地用于临床实践，并可能引起各种不良反应。然而，评估和管理这些反应的明确指导仍然有限。方法我们回顾了2014年5月至2024年4月期间药物过敏诊所REDCap数据库中所有对生物制剂有过敏标签的病例。57例患者的62个生物反应标签（5例为双标签）被纳入研究。图表回顾评估的人口统计、反应史、检测和治疗建议。结果涉及23种独特的生物制剂（表），最常见的是Ustekinumab (10, 16.1%), Evolocumab（7, 11.3%）和英夫利昔单抗（6,9.7%）。出现过敏反应9例（14.5%），其他急性ige型症状5例（8.1%）。非ige介导的反应最为常见（28.45.2%），包括迟发性荨麻疹/血管性水肿（25.0%）、非特异性皮疹（28.6%）、局部反应（21.4%）、神经病变（10.7%）、流感样症状（7.1%）、鼻痒（3.6%）和头晕（3.6%）。严重皮肤不良反应2例（3.2%），输液反应10例（16.1%）。25例（40.3%）进行了检测，包括20例皮肤试验（18例为辅料试验，2例为生物试验），除1例醋酸甲基强的松龙阳性外，均为阴性。两名患者接受了成功的药物挑战。建议包括用药前（33.9%）、继续使用（25.8%）、脱敏（8.1%）、避免使用（16.1%）、改用具有相同赋形剂的另一种生物制剂（9.7%）或同类（6.5%）。结论在评价生物制剂的反应时，大多数反应是非ige介导的，强调了临床病史在评价中的重要性。大多数对生物制剂的过敏似乎不太可能与赋形剂有关。用药前、改良使用和替代生物制剂可有效识别，以确保持续治疗。

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引用次数: 0

BETA-LACTAM ALLERGY LABEL RATES RISE WITH DISTANCE FROM MAIN PEDIATRIC ACADEMIC CENTER β -内酰胺过敏标签率随距离主要儿科学术中心的远近而上升

IF 4.7 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2025-11-01 DOI: 10.1016/j.anai.2025.08.043

J. Atalla, J. Lee

Introduction

Beta-lactam (BL) allergy is common, with 10% of patients in the US reporting a penicillin (PCN) allergy. BL and PCN allergy labels are associated with various adverse health outcomes.

Methods

Rates of BL allergy labels in pediatric patients were calculated for the various primary care clinics within our care network over a 1-year period. We calculated the distance from each clinic to the main hospital, a large, academic quaternary pediatric hospital.

Results

There were 203,777 patients seen throughout 31 primary care clinics during the timeframe examined. The overall rate of BL allergy label throughout the network was 8.3%. There were 11 sites (35%), servicing 90,971 patients, with BL allergy label rates less than the network average (range 3.7%- 8.25%). These sites had a mean distance of 13.1 miles from the main hospital. There were 8 sites (25.8%), servicing 47,286 patients, with BL allergy rates above network average but below 10% (range 8.41%-9.8%). The mean distance from the main hospital for this group was 30.8 miles. The final 12 sites (38.7%), servicing 65,529 patients, had BL allergy rates above 10% (range 10.15%-13.9%). This group averaged 36.6 miles from the main hospital.

Conclusion

In a large pediatric care network, rates of reported BL allergy appeared to increase with increasing distance from the main hospital. This highlights the importance of including and perhaps targeting more remote care settings in efforts to improve BL and PCN allergy delabeling.

β -内酰胺（BL）过敏很常见，在美国有10%的患者报告青霉素（PCN）过敏。BL和PCN过敏标签与各种不良健康结果相关。方法计算我们的护理网络中各初级保健诊所1年内儿科患者的BL过敏标签率。我们计算了从每个诊所到主医院的距离，主医院是一家大型的学术儿科第四医院。结果在调查的时间段内，31家初级保健诊所共就诊203777例患者。整个网络中BL过敏标签的总体比例为8.3%。有11个站点（35%），服务90,971例患者，BL过敏标签率低于网络平均水平（范围为3.7%- 8.25%）。这些地点与主要医院的平均距离为13.1英里。8个站点（25.8%）共47,286例患者，BL过敏率高于网络平均水平，但低于10%（8.41% ~ 9.8%）。这些人到主要医院的平均距离是30.8英里。最后12个站点（38.7%），服务65,529例患者，BL过敏率高于10%（范围10.15%-13.9%）。这组人平均距离主要医院36.6英里。结论在一个大型儿科护理网络中，报告的BL过敏率随着距离主要医院的距离增加而增加。这突出了包括和可能针对更多的远程护理机构在努力改善BL和PCN过敏标签的重要性。

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引用次数: 0

GENOME-WIDE MULTI-OMIC ANALYSIS OF THE GENETIC ORIGINS OF ASTHMA 哮喘遗传起源的全基因组多组学分析

IF 4.7 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology

Pub Date : 2025-11-01 DOI: 10.1016/j.anai.2025.08.025

H. Knihtila , S. Zhang , M. Snyder

Introduction

Despite over 140 susceptibility loci for asthma identified, these account for only a small fraction of the disease heritability, and the genetic origins of asthma remain poorly understood. To better understand the complex genetic architecture of asthma, we employed a multi-omic approach integrating genome-wide association study (GWAS) data with single-cell chromatin accessibility profiles from fetal lung tissue.

Methods

We investigated genetic risk regions associated with asthma using RefMap, a machine learning framework that combines genetic signals with functional genomic profiling. We combined GWAS results from the Trans-National Asthma Genetic Consortium, a multi-ancestry meta-analysis of 23,948 asthma cases and 118,538 controls with functional annotations from single-cell ATAC-sequencing of 59 fetal lung samples (89 to 125 days post-conceptual age).

Results

Our analysis identified 257 positively and 320 negatively associated genomic asthma risk regions, which we mapped to 532 genes. Gene ontology pathway analysis revealed that these genes were significantly enriched in pathways related to lymphocyte differentiation and regulation, and antigen presentation. Single-cell transcriptome analysis of fetal lung tissue indicated that stromal cells, visceral neurons, and epithelial cells exhibited the highest expression of the risk genes during fetal development.

Conclusion

This multi-omic integrated analysis provides novel insights into the genetic architecture and fetal programming of asthma, identifying lymphocyte signaling and antigen presentation as key enriched pathways. Further characterization of these regions and validation in independent cohorts could uncover regulatory elements influencing asthma susceptibility during lung development, potentially revealing new targets for therapeutic intervention and prevention strategies.

尽管确定了140多个哮喘易感位点，但这些位点仅占疾病遗传性的一小部分，并且哮喘的遗传起源仍然知之甚少。为了更好地了解哮喘的复杂遗传结构，我们采用了一种多组学方法，将全基因组关联研究（GWAS）数据与胎儿肺组织的单细胞染色质可及性谱结合起来。方法使用RefMap（一种结合遗传信号和功能基因组分析的机器学习框架）研究与哮喘相关的遗传风险区域。我们结合了来自跨国哮喘遗传联盟的GWAS结果，这是一项对23,948例哮喘病例和118,538例对照的多祖先荟萃分析，以及来自59个胎儿肺样本（胎龄89至125天）的单细胞atac测序的功能注释。结果我们的分析确定了257个呈正相关的基因组哮喘风险区域和320个负相关的基因组哮喘风险区域，我们将其定位到532个基因。基因本体通路分析显示，这些基因在淋巴细胞分化调控、抗原递呈等相关通路中显著富集。胎儿肺组织的单细胞转录组分析表明，在胎儿发育过程中，基质细胞、内脏神经元和上皮细胞表现出最高的风险基因表达。结论该多组学综合分析为哮喘的遗传结构和胎儿规划提供了新的见解，确定了淋巴细胞信号传导和抗原呈递是关键的富集途径。进一步表征这些区域并在独立队列中进行验证，可能会发现影响肺部发育过程中哮喘易感性的调节因子，从而潜在地揭示治疗干预和预防策略的新靶点。

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引用次数: 0