Jonathan A. Bernstein, Emel Aygören-Pürsün, Mauro Cancian, Danny M. Cohn, Timothy Craig, Vesna Grivcheva-Panovska, Anthony Jordan, William R. Lumry, Inmaculada Martinez-Saguer, Isaac Melamed, Kazumasa Ohmura, Jonny Peter, Marc A. Riedl, Daniel F. Soteres, Petra Staubach, Marcin Stobiecki, Ya-Hsiu Chuang, Michael D. Smith, Christopher M. Yea, Paul K. Audhya, Andrea Zanichelli, Henriette Farkas
Background
Hereditary angioedema (HAE-C1INH) attacks involving mucosal tissue may progress rapidly and often lead to substantial morbidity. Severe laryngeal attacks can be fatal without prompt administration of on-demand treatment. This prespecified interim analysis evaluated the safety and effectiveness of sebetralstat in laryngeal and abdominal attacks in the ongoing, 2-year, open-label extension KONFIDENT-S study (NCT05505916).
Methods
Eligible participants ≥ 12 years with HAE-C1INH self-administered sebetralstat 600 mg film-coated tablets with an optional second dose after 3 h, if warranted. Primary outcome: incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes: times to beginning of symptom relief, reduction in severity, and complete resolution.
Results
At data cutoff (Sep 14, 2024), 32 laryngeal (16 participants) and 533 abdominal only attacks (102 participants) were treated with sebetralstat. Seven (43.8%) participants with laryngeal attacks experienced 14 TEAEs whereas 36 (35.3%) participants with abdominal attacks experienced 91 TEAEs. No difficulty swallowing sebetralstat was reported. Median (IQR) time to treatment: 11.5 min (1.0–34.0) and 20.0 min (1.0–61.0) for laryngeal and abdominal attacks, respectively; time to beginning of symptom relief: 1.29 h (0.76–3.02) and 1.27 h (0.76–3.54); reduction in attack severity: 4.25 h (1.22 to > 12) and 3.52 h (1.26 to > 12); complete attack resolution: 12.69 h (5.11 to > 24) and 15.17 h (4.46 to > 24). Most mucosal attacks that achieved beginning of symptom relief within 12 h did so with a single dose of sebetralstat (laryngeal: 96.0%; abdominal: 95.8%). Conventional on-demand treatment was administered within 12 h for 3 (9.4%) laryngeal and 43 (8.1%) abdominal attacks.
Conclusion
Oral sebetralstat enabled rapid treatment of laryngeal and abdominal attacks of all severities, was well tolerated, and provided early symptom relief.
背景：遗传性血管性水肿（HAE-C1INH）累及粘膜组织的发作可能进展迅速，并经常导致严重的发病率。如果不及时按需治疗，严重的喉部发作可能是致命的。这项预先指定的中期分析在正在进行的为期2年的开放标签扩展KONFIDENT-S研究（NCT05505916）中评估了sebetralstat在喉和腹部发作中的安全性和有效性。方法：符合条件的受试者≥12年，HAE-C1INH患者自行给药sebetralstat 600 mg薄膜包衣片，如果有必要，3小时后可选择第二次给药。主要结局：治疗发生不良事件（teae）的发生率。次要结局：症状开始缓解的时间，严重程度的减轻，和完全解决。结果：在数据截止时（2024年9月14日），32例喉部发作（16例）和533例腹部发作（102例）接受了sebetralstat治疗。7名（43.8%）喉部发作的参与者经历了14次teae，而36名（35.3%）腹部发作的参与者经历了91次teae。未见吞咽sebetralstat困难。治疗的中位（IQR）时间：喉部和腹部发作分别为11.5 min（1.0-34.0）和20.0 min (1.0-61.0)；至症状开始缓解时间：1.29 h（0.76-3.02）、1.27 h (0.76-3.54)；攻击严重程度降低：4.25小时（1.22至> 12）和3.52小时（1.26至> 12）；完全攻击分辨率：12.69小时（5.11至> 24）和15.17小时（4.46至> 24）。大多数在12小时内实现症状开始缓解的粘膜发作是通过单剂量的sebetralstat实现的（喉：96.0%；腹部：95.8%）。3例（9.4%）喉部发作和43例（8.1%）腹部发作在12小时内给予常规按需治疗。结论：口服sebetralstat可快速治疗各种严重程度的喉部和腹部发作，耐受性良好，并能早期缓解症状。
{"title":"Sebetralstat for On-Demand Treatment of Mucosal Hereditary Angioedema Attacks in KONFIDENT-S","authors":"Jonathan A. Bernstein, Emel Aygören-Pürsün, Mauro Cancian, Danny M. Cohn, Timothy Craig, Vesna Grivcheva-Panovska, Anthony Jordan, William R. Lumry, Inmaculada Martinez-Saguer, Isaac Melamed, Kazumasa Ohmura, Jonny Peter, Marc A. Riedl, Daniel F. Soteres, Petra Staubach, Marcin Stobiecki, Ya-Hsiu Chuang, Michael D. Smith, Christopher M. Yea, Paul K. Audhya, Andrea Zanichelli, Henriette Farkas","doi":"10.1002/clt2.70118","DOIUrl":"10.1002/clt2.70118","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hereditary angioedema (HAE-C1INH) attacks involving mucosal tissue may progress rapidly and often lead to substantial morbidity. Severe laryngeal attacks can be fatal without prompt administration of on-demand treatment. This prespecified interim analysis evaluated the safety and effectiveness of sebetralstat in laryngeal and abdominal attacks in the ongoing, 2-year, open-label extension KONFIDENT-S study (NCT05505916).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eligible participants ≥ 12 years with HAE-C1INH self-administered sebetralstat 600 mg film-coated tablets with an optional second dose after 3 h, if warranted. Primary outcome: incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes: times to beginning of symptom relief, reduction in severity, and complete resolution.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At data cutoff (Sep 14, 2024), 32 laryngeal (16 participants) and 533 abdominal only attacks (102 participants) were treated with sebetralstat. Seven (43.8%) participants with laryngeal attacks experienced 14 TEAEs whereas 36 (35.3%) participants with abdominal attacks experienced 91 TEAEs. No difficulty swallowing sebetralstat was reported. Median (IQR) time to treatment: 11.5 min (1.0–34.0) and 20.0 min (1.0–61.0) for laryngeal and abdominal attacks, respectively; time to beginning of symptom relief: 1.29 h (0.76–3.02) and 1.27 h (0.76–3.54); reduction in attack severity: 4.25 h (1.22 to > 12) and 3.52 h (1.26 to > 12); complete attack resolution: 12.69 h (5.11 to > 24) and 15.17 h (4.46 to > 24). Most mucosal attacks that achieved beginning of symptom relief within 12 h did so with a single dose of sebetralstat (laryngeal: 96.0%; abdominal: 95.8%). Conventional on-demand treatment was administered within 12 h for 3 (9.4%) laryngeal and 43 (8.1%) abdominal attacks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Oral sebetralstat enabled rapid treatment of laryngeal and abdominal attacks of all severities, was well tolerated, and provided early symptom relief.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 11","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12626162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548604","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}
Hugo Viegas, Bernardo Sousa-Pinto, Rafael José Vieira, Aiste Ramanauskaite, Ellen Witte-Händel, Ana Gimenez-Arnau, Carole Guillet, Claudio Alberto Salvador Parisi, Constance Katelaris, Daria Fomina, Désirée Larenas-Linnemann, Jorge Sánchez, Elizabeth Garcia, Hermenio Lima, Igor Kaidashev, Iman Nasr, Isabel Ogueta Canales, Ivan Cherrez-Ojeda, Jean Bousquet, Jonathan A. Bernstein, Jonny Peter, Jose Ignacio Larco Sousa, Kanokvalai Kulthanan, Karsten Weller, Kiran Godse, Krzysztof Rutkowski, Lasma Lapina, Laurence Bouillet, Luis Felipe Ensina, Margarida Gonçalo, Maria Staevska, Mariam Ali Yousuf Al-Nesf, Markus Magerl, Martin Metz, Martijn van Doorn, Mary Anne Castor, Maryam Khoshkhui, Michael Makris, Michihiro Hide, Mohamad Abuzakouk, Mona Al-Ahmad, Murat Türk, Natasa Teovska Mitrevska, Niall Conlon, Nicole Nojarov, Pavel Kolkhir, Philip Li, Ramzy Mohammed Ali, Rand Arnaout, Riccardo Asero, Sabine Altrichter, Simon Francis Thomsen, Young-Min Ye, Zenon Brzoza, Zuotao Zhao, Torsten Zuberbier, Frank Siebenhaar, Emek Kocatürk, Sophia Neisinger
Background
Mobile health technologies may improve the management of chronic diseases, such as chronic spontaneous urticaria. However, effectiveness of mHealth tools largely depends on patient adherence, which can be influenced by various demographic, clinical, behavioural, psychosocial factors, and apps characteristics (appealing and simplicity of use). Understanding these adherence patterns is crucial for optimizing mHealth interventions. In this study, we aimed to assess adherence patterns associated to the use of CRUSE, a mHealth app designed for patients with CSU.
Methods
We assessed users of the CRUSE app with self-reported CSU or suggested by a physician. For each user, we evaluated the number of days they completed the CRUSE daily monitoring questionnaire (app adherence) within the first 3 months after installation. We constructed univariable and multivariable ordered beta regression models to identify predictors of 3-month adherence to the app.
Results
We analysed data from 2085 patients (66,114 days). Median adherence to the CRUSE app was of 22 days (24.4% of 90 days). In multivariable regression models, the variables more strongly associated with increased adherence to CRUSE included age (average increase = 0.16 percent points [pp] per additional year; 95% credible interval [CrI] = 0.08; 0.23 pp), male sex (average difference = 4.24 pp; 95% CrI = 1.77; 6.39 pp), being from a European country (average difference = 2.66 pp; 95% CrI = 0.59; 5.19 pp), and using monoclonal antibodies (average difference = 4.60 pp; 95% CrI = 2.26; 6.65 pp).
Conclusions
Our findings suggest that age, male sex, residence in Europe, and the use of monoclonal antibodies are significant factors associated with increased adherence to the CRUSE app. These insights may help identify patient subgroups who would benefit most from mHealth support in managing CSU.
{"title":"Key Predictors of Adherence to a Mobile Health App for Managing Chronic Spontaneous Urticaria","authors":"Hugo Viegas, Bernardo Sousa-Pinto, Rafael José Vieira, Aiste Ramanauskaite, Ellen Witte-Händel, Ana Gimenez-Arnau, Carole Guillet, Claudio Alberto Salvador Parisi, Constance Katelaris, Daria Fomina, Désirée Larenas-Linnemann, Jorge Sánchez, Elizabeth Garcia, Hermenio Lima, Igor Kaidashev, Iman Nasr, Isabel Ogueta Canales, Ivan Cherrez-Ojeda, Jean Bousquet, Jonathan A. Bernstein, Jonny Peter, Jose Ignacio Larco Sousa, Kanokvalai Kulthanan, Karsten Weller, Kiran Godse, Krzysztof Rutkowski, Lasma Lapina, Laurence Bouillet, Luis Felipe Ensina, Margarida Gonçalo, Maria Staevska, Mariam Ali Yousuf Al-Nesf, Markus Magerl, Martin Metz, Martijn van Doorn, Mary Anne Castor, Maryam Khoshkhui, Michael Makris, Michihiro Hide, Mohamad Abuzakouk, Mona Al-Ahmad, Murat Türk, Natasa Teovska Mitrevska, Niall Conlon, Nicole Nojarov, Pavel Kolkhir, Philip Li, Ramzy Mohammed Ali, Rand Arnaout, Riccardo Asero, Sabine Altrichter, Simon Francis Thomsen, Young-Min Ye, Zenon Brzoza, Zuotao Zhao, Torsten Zuberbier, Frank Siebenhaar, Emek Kocatürk, Sophia Neisinger","doi":"10.1002/clt2.70110","DOIUrl":"10.1002/clt2.70110","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mobile health technologies may improve the management of chronic diseases, such as chronic spontaneous urticaria. However, effectiveness of mHealth tools largely depends on patient adherence, which can be influenced by various demographic, clinical, behavioural, psychosocial factors, and apps characteristics (appealing and simplicity of use). Understanding these adherence patterns is crucial for optimizing mHealth interventions. In this study, we aimed to assess adherence patterns associated to the use of CRUSE, a mHealth app designed for patients with CSU.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We assessed users of the CRUSE app with self-reported CSU or suggested by a physician. For each user, we evaluated the number of days they completed the CRUSE daily monitoring questionnaire (app adherence) within the first 3 months after installation. We constructed univariable and multivariable ordered beta regression models to identify predictors of 3-month adherence to the app.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We analysed data from 2085 patients (66,114 days). Median adherence to the CRUSE app was of 22 days (24.4% of 90 days). In multivariable regression models, the variables more strongly associated with increased adherence to CRUSE included age (average increase = 0.16 percent points [pp] per additional year; 95% credible interval [CrI] = 0.08; 0.23 pp), male sex (average difference = 4.24 pp; 95% CrI = 1.77; 6.39 pp), being from a European country (average difference = 2.66 pp; 95% CrI = 0.59; 5.19 pp), and using monoclonal antibodies (average difference = 4.60 pp; 95% CrI = 2.26; 6.65 pp).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings suggest that age, male sex, residence in Europe, and the use of monoclonal antibodies are significant factors associated with increased adherence to the CRUSE app. These insights may help identify patient subgroups who would benefit most from mHealth support in managing CSU.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 11","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12619656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530609","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}
Eunice Dias de Castro, Luís Miguel Cardoso, João Jácome de Castro, Manuel Branco Ferreira
Background
Danazol and other attenuated androgens (AAs) have been a cornerstone of Hereditary Angioedema (HAE) long-term prophylaxis (LTP) for decades, alongside intravenous plasma-derived C1INH (pdC1INH). Danazol's potential androgenic effects, however, present several limitations to its prescription and use. With the emergence of safer and more effective LTP drugs, guidelines are now shifting danazol to a second-line option. These changes in HAE therapy require a new framework to guide physicians in the appropriate use of danazol in HAE LTP.
Methods
This study aimed to develop a consensus on key aspects of danazol management, including discontinuation strategies, through a 2-round Delphi methodology. Statements were defined by a steering committee of both Endocrinology and Allergy and Clinical Immunology specialists, considering the available evidence. A panel of 23 experts in HAE management voted on the statements to reach a consensus.
Results
This process resulted in 46 recommendations for the prescription, monitoring, and discontinuation of danazol in LTP, proposing specific strategies for appropriate danazol use. A consensus was achieved on contraindications for danazol usage in LTP, detailed parameters for ongoing monitoring, and instructions for therapy adjustment considering treatment effect and using patient-reported outcomes. Furthermore, seven recommendations provide guidance on the increasingly relevant challenge of danazol discontinuation in HAE patients.
Conclusion
This Delphi study specifically addresses the gap in clinical guidance for danazol management in HAE patients. The resulting consensus document provides a valuable tool to aid the standardization of danazol discontinuation protocols and ensures that patients can access the safest and most effective treatment options available.
{"title":"Delphi Consensus on Attenuated Androgen Use for Long-Term Prophylaxis in Hereditary Angioedema: AURA Project","authors":"Eunice Dias de Castro, Luís Miguel Cardoso, João Jácome de Castro, Manuel Branco Ferreira","doi":"10.1002/clt2.70116","DOIUrl":"10.1002/clt2.70116","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Danazol and other attenuated androgens (AAs) have been a cornerstone of Hereditary Angioedema (HAE) long-term prophylaxis (LTP) for decades, alongside intravenous plasma-derived C1INH (pdC1INH). Danazol's potential androgenic effects, however, present several limitations to its prescription and use. With the emergence of safer and more effective LTP drugs, guidelines are now shifting danazol to a second-line option. These changes in HAE therapy require a new framework to guide physicians in the appropriate use of danazol in HAE LTP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study aimed to develop a consensus on key aspects of danazol management, including discontinuation strategies, through a 2-round Delphi methodology. Statements were defined by a steering committee of both Endocrinology and Allergy and Clinical Immunology specialists, considering the available evidence. A panel of 23 experts in HAE management voted on the statements to reach a consensus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This process resulted in 46 recommendations for the prescription, monitoring, and discontinuation of danazol in LTP, proposing specific strategies for appropriate danazol use. A consensus was achieved on contraindications for danazol usage in LTP, detailed parameters for ongoing monitoring, and instructions for therapy adjustment considering treatment effect and using patient-reported outcomes. Furthermore, seven recommendations provide guidance on the increasingly relevant challenge of danazol discontinuation in HAE patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This Delphi study specifically addresses the gap in clinical guidance for danazol management in HAE patients. The resulting consensus document provides a valuable tool to aid the standardization of danazol discontinuation protocols and ensures that patients can access the safest and most effective treatment options available.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 11","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12606019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494725","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}
Jorge Sánchez, Gabriel Montoya, Ana Caraballo, María-Fernanda Ordoñez-Rubiano, Margarita Velasquez, Claudia Arenas, Julián Londoño, Elizabeth García
Background
Sexual health in patients with atopic dermatitis (AD) remains scarcely studied. Identifying the problematic of sexual health disorders (SHD) in AD and associated factors is important for the design and implementation of targeted interventions.
Objective
To describe the frequency of sexual health disorders (SHD) in AD patients, identify risk factors and assess whether improved AD control with pharmacotherapy is associated with changes in SHD.
Methods
We performed a prospective observational study in AD patients over 18 years of age. Participants completed a survey assessing clinical aspects of SHD and AD at baseline and 5–7 months after initiating specialists-recommended treatment. For AD severity evaluation we used SCORAD and POEM scales and for SHD we used SyDSF-AP, IFSF, and MGH-SFQ.
Results
A total of 221 AD patients were enrolled. At baseline, the frequency of SHD varied according to AD severity (SHD in severe AD 100%, in moderate AD 96%, and in mild AD 56%). Risk factors for SHD were AD severity (SCORAD OR 3.88 [95% CI 2.68–4.73], POEM OR 4.67 [95% CI 3.05–5.79]), skin area affected (OR 3.15 [95% CI 2.88–5.19]), and disease duration (OR 3.75 [95% CI 1.88–4.91]). Improved AD control through pharmacotherapy reduced SHD frequency in mild AD (relative reduction [RR]: −60%), moderate AD (RR: −41%), and severe AD (RR: −28%).
Conclusion
Atopic dermatitis was frequently associated with SHD even in mild forms of the disease. However, AD clinical control reduced the frequency of SHD, and consequently improving the quality of life of patients.
背景：特应性皮炎（AD）患者的性健康研究仍然很少。识别AD中的性健康障碍（SHD）问题及其相关因素对于设计和实施有针对性的干预措施非常重要。目的：描述AD患者性健康障碍（SHD）的频率，识别危险因素，并评估药物治疗改善AD控制是否与SHD的改变有关。方法：我们对18岁以上的AD患者进行了一项前瞻性观察研究。参与者完成了一项调查，评估SHD和AD在基线和开始专家推荐治疗后5-7个月的临床方面。对于AD的严重程度评估，我们使用SCORAD和POEM量表，对于SHD，我们使用SyDSF-AP， IFSF和MGH-SFQ量表。结果：共纳入221例AD患者。在基线时，SHD的频率根据AD的严重程度而变化（重度AD为100%，中度AD为96%，轻度AD为56%）。SHD的危险因素为AD严重程度（SCORAD OR 3.88 [95% CI 2.68-4.73], POEM OR 4.67 [95% CI 3.05-5.79]）、皮肤受影响面积（OR 3.15 [95% CI 2.88-5.19]）和疾病持续时间（OR 3.75 [95% CI 1.88-4.91]）。通过药物治疗改善AD控制可降低轻度AD（相对降低[RR]: -60%）、中度AD（相对降低[RR]: -41%）和重度AD（相对降低：-28%）的SHD频率。结论：特应性皮炎经常与SHD相关，即使是在轻度的疾病形式。然而，AD临床控制降低了SHD的发生频率，从而提高了患者的生活质量。
{"title":"Sexual Health in Atopic Dermatitis: Impact of Skin Clinical Control","authors":"Jorge Sánchez, Gabriel Montoya, Ana Caraballo, María-Fernanda Ordoñez-Rubiano, Margarita Velasquez, Claudia Arenas, Julián Londoño, Elizabeth García","doi":"10.1002/clt2.70115","DOIUrl":"10.1002/clt2.70115","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sexual health in patients with atopic dermatitis (AD) remains scarcely studied. Identifying the problematic of sexual health disorders (SHD) in AD and associated factors is important for the design and implementation of targeted interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To describe the frequency of sexual health disorders (SHD) in AD patients, identify risk factors and assess whether improved AD control with pharmacotherapy is associated with changes in SHD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a prospective observational study in AD patients over 18 years of age. Participants completed a survey assessing clinical aspects of SHD and AD at baseline and 5–7 months after initiating specialists-recommended treatment. For AD severity evaluation we used SCORAD and POEM scales and for SHD we used SyDSF-AP, IFSF, and MGH-SFQ.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 221 AD patients were enrolled. At baseline, the frequency of SHD varied according to AD severity (SHD in severe AD 100%, in moderate AD 96%, and in mild AD 56%). Risk factors for SHD were AD severity (SCORAD OR 3.88 [95% CI 2.68–4.73], POEM OR 4.67 [95% CI 3.05–5.79]), skin area affected (OR 3.15 [95% CI 2.88–5.19]), and disease duration (OR 3.75 [95% CI 1.88–4.91]). Improved AD control through pharmacotherapy reduced SHD frequency in mild AD (relative reduction [RR]: −60%), moderate AD (RR: −41%), and severe AD (RR: −28%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Atopic dermatitis was frequently associated with SHD even in mild forms of the disease. However, AD clinical control reduced the frequency of SHD, and consequently improving the quality of life of patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 11","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12596026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476798","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}
Chen Zhang, Qianqian Zhang, Jiani Chen, Fuying Cheng, Yizhang Wang, Shirui Xue, Yufei Yang, Wenwen Guo, Juan Liu, Dehui Wang, Li Hu, Xicai Sun, Huan Wang, Quan Liu
Background
Chronic rhinosinusitis with nasal polyps (CRSwNP) significantly impairs the quality of life, and disease control is now considered the primary treatment goal. Although patient-reported outcome measures (PROMs) such as the 22-item Sinonasal Outcome Test (SNOT-22) and CRS-PRO are widely used, their utility in predicting long-term postoperative disease control remains limited.
Methods
This prospective follow-up study aimed to evaluate postoperative recovery and identify the predictors of suboptimal disease control in patients with CRSwNP by integrating preoperative PROMs with objective clinical features. A total of 102 patients with CRSwNP undergoing functional endoscopic sinus surgery (FESS) were enrolled, of whom 89 completed at least 12 months of follow-up. Preoperative and postoperative PROMs were compared across disease control groups classified based on the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 criteria. Least absolute shrinkage and selection operator regression was applied to select objective clinical predictors, which were then combined with either CRS-PRO or SNOT-22 item scores to develop and compare the nine machine learning models. Model performance was assessed using area under the curve (AUC), decision curve analysis, sensitivity, specificity, and other metrics.
Results
Eosinophil and neutrophil counts were identified as key objective predictors of suboptimal disease control after FESS. Among all models, logistic regression incorporating CRS-PRO scores and selected clinical features achieved the best performance, yielding an AUC of 0.866, accuracy of 83.3%, sensitivity of 72.7%, specificity of 89.5%, and F1-score of 76.2%. This model demonstrated a strong discriminatory ability and potential utility in individualized clinical decision-making.
Conclusion
Integrating preoperative CRS-PRO item scores with selected objective clinical parameters enables the accurate prediction of suboptimal disease control in patients with CRSwNP following FESS. This approach supports personalized risk stratification and postoperative management strategies.
{"title":"Patient-Reported Outcome Measures as Predictive Tools for Disease Control in Chronic Rhinosinusitis With Nasal Polyps: A Prospective Study","authors":"Chen Zhang, Qianqian Zhang, Jiani Chen, Fuying Cheng, Yizhang Wang, Shirui Xue, Yufei Yang, Wenwen Guo, Juan Liu, Dehui Wang, Li Hu, Xicai Sun, Huan Wang, Quan Liu","doi":"10.1002/clt2.70119","DOIUrl":"10.1002/clt2.70119","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic rhinosinusitis with nasal polyps (CRSwNP) significantly impairs the quality of life, and disease control is now considered the primary treatment goal. Although patient-reported outcome measures (PROMs) such as the 22-item Sinonasal Outcome Test (SNOT-22) and CRS-PRO are widely used, their utility in predicting long-term postoperative disease control remains limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective follow-up study aimed to evaluate postoperative recovery and identify the predictors of suboptimal disease control in patients with CRSwNP by integrating preoperative PROMs with objective clinical features. A total of 102 patients with CRSwNP undergoing functional endoscopic sinus surgery (FESS) were enrolled, of whom 89 completed at least 12 months of follow-up. Preoperative and postoperative PROMs were compared across disease control groups classified based on the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 criteria. Least absolute shrinkage and selection operator regression was applied to select objective clinical predictors, which were then combined with either CRS-PRO or SNOT-22 item scores to develop and compare the nine machine learning models. Model performance was assessed using area under the curve (AUC), decision curve analysis, sensitivity, specificity, and other metrics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eosinophil and neutrophil counts were identified as key objective predictors of suboptimal disease control after FESS. Among all models, logistic regression incorporating CRS-PRO scores and selected clinical features achieved the best performance, yielding an AUC of 0.866, accuracy of 83.3%, sensitivity of 72.7%, specificity of 89.5%, and F1-score of 76.2%. This model demonstrated a strong discriminatory ability and potential utility in individualized clinical decision-making.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Integrating preoperative CRS-PRO item scores with selected objective clinical parameters enables the accurate prediction of suboptimal disease control in patients with CRSwNP following FESS. This approach supports personalized risk stratification and postoperative management strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 11","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12584042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437726","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}
Direct comparative efficacy data for biologics in chronic rhinosinusitis with nasal polyps (CRSwNP) remain limited, particularly for novel agents like tezepelumab, underscoring the need to identify optimal therapies for precision management.
Objective
To rank the comparative efficacy and safety of dupilumab, tezepelumab, omalizumab, and mepolizumab versus placebo for CRSwNP using network meta-analysis.
Methods
PubMed, Embase, Web of Science, and Cochrane Library were searched from inception through April 1, 2025. Randomized controlled trials (RCTs) in adults with CRSwNP comparing biologics against placebo were eligible. PRISMA-NMA guidelines were followed. GRADE methodology was employed for evidence certainty assessment. Two investigators independently extracted data. Fixed-effect model network meta-analysis was performed, with treatments ranked via surface under the cumulative ranking curve (SUCRA). The primary outcomes were Nasal Polyp Score (NPS) and safety metrics (proportion of participants with ≥ 1 adverse event). Secondary outcomes included Sino-Nasal Outcome Test-22 (SNOT-22), University of Pennsylvania Smell Identification Test (UPSIT), and Nasal Congestion Score (NCS).
Results
Thirteen RCTs (n = 2304) evaluating four biologics versus placebo were included. Compared to placebo, NPS was significantly improved by dupilumab (WMD: −2.16, 95% CI [−2.44, −1.89]), omalizumab (WMD: 1.25, 95% CI [−1.52, −0.97]), mepolizumab (WMD: 0.90, 95% CI [−1.19, −0.62]), and tezepelumab (WMD: −1.50, 95% CI [−1.81, −1.19]). Dupilumab ranked first in efficacy outcomes (NPS, SNOT-22, UPSIT, and NCS, SUCRA ≥ 0.900, respectively). Tezepelumab ranked second in NPS (SUCRA: 0.720) and UPSIT (SUCRA: 0.749), while omalizumab ranked first in safety (SUCRA of adverse events: 0.064). GRADE assessments indicated that the certainty of the evidence was predominantly high for these key efficacy comparisons.
Conclusions
Dupilumab demonstrated the highest efficacy and safety profile. Tezepelumab showed comparable efficacy in NPS with omalizumab.
{"title":"Which Is the Best Biologic for Nasal Polyps: An Updated Network Meta-Analysis","authors":"Xi Xu, Jinting Lin, Minting Luo, Qingwu Wu","doi":"10.1002/clt2.70114","DOIUrl":"https://doi.org/10.1002/clt2.70114","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Direct comparative efficacy data for biologics in chronic rhinosinusitis with nasal polyps (CRSwNP) remain limited, particularly for novel agents like tezepelumab, underscoring the need to identify optimal therapies for precision management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To rank the comparative efficacy and safety of dupilumab, tezepelumab, omalizumab, and mepolizumab versus placebo for CRSwNP using network meta-analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PubMed, Embase, Web of Science, and Cochrane Library were searched from inception through April 1, 2025. Randomized controlled trials (RCTs) in adults with CRSwNP comparing biologics against placebo were eligible. PRISMA-NMA guidelines were followed. GRADE methodology was employed for evidence certainty assessment. Two investigators independently extracted data. Fixed-effect model network meta-analysis was performed, with treatments ranked via surface under the cumulative ranking curve (SUCRA). The primary outcomes were Nasal Polyp Score (NPS) and safety metrics (proportion of participants with ≥ 1 adverse event). Secondary outcomes included Sino-Nasal Outcome Test-22 (SNOT-22), University of Pennsylvania Smell Identification Test (UPSIT), and Nasal Congestion Score (NCS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirteen RCTs (<i>n</i> = 2304) evaluating four biologics versus placebo were included. Compared to placebo, NPS was significantly improved by dupilumab (WMD: −2.16, 95% CI [−2.44, −1.89]), omalizumab (WMD: 1.25, 95% CI [−1.52, −0.97]), mepolizumab (WMD: 0.90, 95% CI [−1.19, −0.62]), and tezepelumab (WMD: −1.50, 95% CI [−1.81, −1.19]). Dupilumab ranked first in efficacy outcomes (NPS, SNOT-22, UPSIT, and NCS, SUCRA ≥ 0.900, respectively). Tezepelumab ranked second in NPS (SUCRA: 0.720) and UPSIT (SUCRA: 0.749), while omalizumab ranked first in safety (SUCRA of adverse events: 0.064). GRADE assessments indicated that the certainty of the evidence was predominantly high for these key efficacy comparisons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Dupilumab demonstrated the highest efficacy and safety profile. Tezepelumab showed comparable efficacy in NPS with omalizumab.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 11","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426107","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}
Manuela Latorre, Pierluigi Paggiaro, Cristina Cardini, Giovanni Paoletti, Emanuele Nappi, Mario Di Gioacchino, Enrico Heffler, Francesco Blasi, Giorgio Walter Canonica, Francesca Puggioni, SANI Network
Background
The rapid digital transformation has significantly impacted healthcare, particularly through eHealth solutions that offer great potential for managing chronic respiratory conditions such as asthma. This study explores the impact, attitudes, and acceptance of digital technologies in asthma management in Italy.
Methods
A structured 34-item survey, developed in two versions for patients and physicians, was administered independently and anonymously to adult asthma patients and to specialists in pulmonology and allergology. The questionnaires collected data on demographics, professional background, digital habits (for work and leisure), use of digital tools such as apps and smart inhalers, doctor–patient digital communication, familiarity with online health resources, and perceived barriers to digital adoption. Data were collected anonymously via REDCap, with oversight from the Severe Asthma Network in Italy (SANI).
Results
A total of 134 patients and 180 doctors participated. Findings revealed a predominantly positive attitude toward digital tools, with 85% of physicians and 74.4% of patients embracing a “digital mindset.” Nevertheless, digital innovations remain underutilized in clinical practice. While 85.6% of patients reported regularly using digital tools in their daily lives, 91.5% stated that their doctors had never recommended apps or websites for asthma self-management. Digital solutions such as mobile apps, wearable spirometers, and telemedicine are recognized for their potential benefits—clinicians highlighted symptoms self-tracking (17.2%), improved adherence (22.7%), and enhanced clinical interventions (11.7%) as key advantages. However, adoption is hindered by concerns such as information technology (IT) compliance (62.5%), legal risks (11.5%), and skepticism about the reliability of remote data (40.6%). Furthermore, 59.9% of clinicians and 66.8% of patients recognized a knowledge gap regarding the potential benefits of smart inhalers and digital therapeutics in respiratory care.
Conclusion
The study highlights a positive attitude toward digital tools in asthma management but reveals limited adoption in clinical practice. Key barriers include IT compliance concerns and knowledge gaps. Addressing these challenges through education and regulatory support could enhance digital integration, improving asthma care.
{"title":"Digital Innovation in Asthma Management in Italy: Results From the “Confronting Asthma Survey”","authors":"Manuela Latorre, Pierluigi Paggiaro, Cristina Cardini, Giovanni Paoletti, Emanuele Nappi, Mario Di Gioacchino, Enrico Heffler, Francesco Blasi, Giorgio Walter Canonica, Francesca Puggioni, SANI Network","doi":"10.1002/clt2.70109","DOIUrl":"10.1002/clt2.70109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The rapid digital transformation has significantly impacted healthcare, particularly through eHealth solutions that offer great potential for managing chronic respiratory conditions such as asthma. This study explores the impact, attitudes, and acceptance of digital technologies in asthma management in Italy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A structured 34-item survey, developed in two versions for patients and physicians, was administered independently and anonymously to adult asthma patients and to specialists in pulmonology and allergology. The questionnaires collected data on demographics, professional background, digital habits (for work and leisure), use of digital tools such as apps and smart inhalers, doctor–patient digital communication, familiarity with online health resources, and perceived barriers to digital adoption. Data were collected anonymously via REDCap, with oversight from the Severe Asthma Network in Italy (SANI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 134 patients and 180 doctors participated. Findings revealed a predominantly positive attitude toward digital tools, with 85% of physicians and 74.4% of patients embracing a “digital mindset.” Nevertheless, digital innovations remain underutilized in clinical practice. While 85.6% of patients reported regularly using digital tools in their daily lives, 91.5% stated that their doctors had never recommended apps or websites for asthma self-management. Digital solutions such as mobile apps, wearable spirometers, and telemedicine are recognized for their potential benefits—clinicians highlighted symptoms self-tracking (17.2%), improved adherence (22.7%), and enhanced clinical interventions (11.7%) as key advantages. However, adoption is hindered by concerns such as information technology (IT) compliance (62.5%), legal risks (11.5%), and skepticism about the reliability of remote data (40.6%). Furthermore, 59.9% of clinicians and 66.8% of patients recognized a knowledge gap regarding the potential benefits of smart inhalers and digital therapeutics in respiratory care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study highlights a positive attitude toward digital tools in asthma management but reveals limited adoption in clinical practice. Key barriers include IT compliance concerns and knowledge gaps. Addressing these challenges through education and regulatory support could enhance digital integration, improving asthma care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307311","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}
Chang Li, Jie Liu, Xiaoshi Li, Wenlong Chen, Ying Zhang, Heng Sun, Cunni Zheng, Quan Liu
Background
Although IL-33/ST2 signaling has been implicated in adult asthma, its contribution to early-onset allergic asthma remains poorly understood. Here, we examined the postnatal dynamics of IL-33 and its regulation by splenic ST2+ erythroid progenitors (EPs).
Methods
Plasma IL-33 levels were measured in neonatal and young mice. Wild Type (WT) and Il33−/− mice were exposed to house dust mite (HDM) to assess airway inflammation and asthma. ST2+ EPs were analyzed for IL-33 responsiveness, transcriptomic/epigenomic profiles, and IL-33 scavenging capacity. EP depletion was performed to evaluate their role in HDM-induced inflammation.
Results
Plasma IL-33 levels fluctuated during the postnatal period, peaking at postnatal day 7 (PND7). WT mice exhibited more severe HDM-induced airway inflammation than Il33−/− mice. Splenic ST2+ EPs, abundant in early life but absent by PND28, displayed minimal IL-33–induced signaling or transcriptomic/epigenomic alterations, yet efficiently scavenged IL-33. Depletion of EPs exacerbated HDM-induced inflammation, accompanied by increased T follicular helper cells (Tfh) and IgE+ B cells.
Conclusion
ST2+ EPs function as transient IL-33 scavengers during early life, attenuating its pro-asthmatic effects and preserving immune homeostasis.
{"title":"ST2+ Erythroid Progenitors Suppress Allergic Asthma by Scavenging IL-33 in Young Mice","authors":"Chang Li, Jie Liu, Xiaoshi Li, Wenlong Chen, Ying Zhang, Heng Sun, Cunni Zheng, Quan Liu","doi":"10.1002/clt2.70111","DOIUrl":"10.1002/clt2.70111","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although IL-33/ST2 signaling has been implicated in adult asthma, its contribution to early-onset allergic asthma remains poorly understood. Here, we examined the postnatal dynamics of IL-33 and its regulation by splenic ST2<sup>+</sup> erythroid progenitors (EPs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Plasma IL-33 levels were measured in neonatal and young mice. Wild Type (WT) and <i>Il33</i><sup>−/−</sup> mice were exposed to house dust mite (HDM) to assess airway inflammation and asthma. ST2<sup>+</sup> EPs were analyzed for IL-33 responsiveness, transcriptomic/epigenomic profiles, and IL-33 scavenging capacity. EP depletion was performed to evaluate their role in HDM-induced inflammation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Plasma IL-33 levels fluctuated during the postnatal period, peaking at postnatal day 7 (PND7). WT mice exhibited more severe HDM-induced airway inflammation than <i>Il33</i><sup>−/−</sup> mice. Splenic ST2<sup>+</sup> EPs, abundant in early life but absent by PND28, displayed minimal IL-33–induced signaling or transcriptomic/epigenomic alterations, yet efficiently scavenged IL-33. Depletion of EPs exacerbated HDM-induced inflammation, accompanied by increased T follicular helper cells (Tfh) and IgE<sup>+</sup> B cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ST2<sup>+</sup> EPs function as transient IL-33 scavengers during early life, attenuating its pro-asthmatic effects and preserving immune homeostasis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312581","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}
Zhuoran Li, Jean Schneikert, Anja Wegner, Torsten Zuberbier, Magda Babina
Background
MRGPRX2, a receptor central to mast cell (MC) activation and related skin diseases, is selectively expressed in skin MCs but downregulated during culture by stem cell factor (SCF) and interleukin-4 (IL-4).
Objective
To identify culture conditions that preserve MC viability while restoring MRGPRX2 expression and function.
Methods
Human skin MCs were cultured in standard or serum-free Accell medium (both with SCF). After 3 days, MRGPRX2 expression was assessed by flow cytometry, degranulation by mediator release assays, and signaling by Western blotting.
Results
Accell medium increased MRGPRX2 expression to ~1.7-fold and enhanced degranulation to Substance P and codeine. It also promoted stronger and more sustained ERK and AKT phosphorylation, while FcεRI-mediated responses were largely unaffected.
Conclusion
Short-term incubation in serum-free Accell medium restores MRGPRX2 expression and signaling in cultured skin MCs without impairing viability. This simple adjustment yields a practical and reliable model for MRGPRX2-focused studies.
{"title":"A Novel Cell Culture System to Improve MRGPRX2 Research in Human Skin Mast Cells","authors":"Zhuoran Li, Jean Schneikert, Anja Wegner, Torsten Zuberbier, Magda Babina","doi":"10.1002/clt2.70112","DOIUrl":"10.1002/clt2.70112","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>MRGPRX2, a receptor central to mast cell (MC) activation and related skin diseases, is selectively expressed in skin MCs but downregulated during culture by stem cell factor (SCF) and interleukin-4 (IL-4).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To identify culture conditions that preserve MC viability while restoring MRGPRX2 expression and function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Human skin MCs were cultured in standard or serum-free Accell medium (both with SCF). After 3 days, MRGPRX2 expression was assessed by flow cytometry, degranulation by mediator release assays, and signaling by Western blotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Accell medium increased MRGPRX2 expression to ~1.7-fold and enhanced degranulation to Substance P and codeine. It also promoted stronger and more sustained ERK and AKT phosphorylation, while FcεRI-mediated responses were largely unaffected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Short-term incubation in serum-free Accell medium restores MRGPRX2 expression and signaling in cultured skin MCs without impairing viability. This simple adjustment yields a practical and reliable model for MRGPRX2-focused studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12529870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299115","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}
Aleksandra Górska, Thierry van De Wetering, Marta Sobalska-Kwapis, Bogusław Nedoszytko, Danuta Gutowska-Owsiak, Marek Niedoszytko
Aim
Mastocytosis is a neoplastic disease of the bone marrow associated with the risk of frequent and severe allergic reactions. However, the genetic predisposition is not fully understood, and the crucial element in pathogenesis is the presence of the oncogenic KIT p. D816 V gene mutation. The epigenetic mechanism has also been suggested as playing a role in mastocytosis.
Objective
Based on our previous epigenetic studies, we have selected 110 candidate genes which were sequenced by next generation sequencing (NGS) to identify somatic mutations.
Method
The study group consisted of 32 patients with mastocytosis (16 females and 16 males) plus 16 controls (8 females and 8 males). Whole peripheral blood was collected from all the subjects and genotyped by NGS on the Illumina platform (targeted sequencing).
Results
We analysed 4272 genetic variations in the pre-selected candidate genes and found five regions that showed a significant difference between the patient and control group. Two of them were found in the TET2 gene located on chromosome 4 and the other three alterations were found in the genes DNMT3A, SETD2 and BRD4 located on chromosomes 2, 3 and 19, respectively. Two out of the five genetic variants have not been previously reported, despite the fact that all four genes have been described to be associated with mastocytosis.
Conclusions
The results align with our previous findings, which determined TET2, DNMT3A, SETD2 and BRD4 genes as promising candidates for further analysis, warranting future study in a larger cohort of mastocytosis patients.
目的：肥大细胞增多症是一种与频繁和严重过敏反应风险相关的骨髓肿瘤疾病。然而，遗传易感性尚不完全清楚，发病机制的关键因素是致癌的KIT p. d816v基因突变的存在。表观遗传机制也被认为在肥大细胞增多症中起作用。目的：在前人表观遗传学研究的基础上，选择110个候选基因，通过下一代测序（NGS）进行体细胞突变鉴定。方法：研究组32例肥大细胞增多症患者（女16例，男16例）加16例对照组（女8例，男8例）。采集所有受试者全外周血，在Illumina平台上进行NGS基因分型（靶向测序）。结果：我们分析了预先选择的候选基因中的4272个遗传变异，发现患者和对照组之间有5个区域表现出显著差异。其中2处位于第4号染色体上的TET2基因，另外3处分别位于第2、3、19号染色体上的DNMT3A、SETD2和BRD4基因。这五种基因变异中有两种以前没有报道过，尽管事实上这四种基因都被描述为与肥大细胞增多症有关。结论：结果与我们之前的研究结果一致，确定TET2、DNMT3A、SETD2和BRD4基因是进一步分析的有希望的候选基因，保证未来在更大的肥大细胞增多症患者队列中进行研究。
{"title":"Next Generation Sequencing of Genes With Epigenetic Alterations in Mastocytosis","authors":"Aleksandra Górska, Thierry van De Wetering, Marta Sobalska-Kwapis, Bogusław Nedoszytko, Danuta Gutowska-Owsiak, Marek Niedoszytko","doi":"10.1002/clt2.70106","DOIUrl":"10.1002/clt2.70106","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Mastocytosis is a neoplastic disease of the bone marrow associated with the risk of frequent and severe allergic reactions. However, the genetic predisposition is not fully understood, and the crucial element in pathogenesis is the presence of the oncogenic KIT p. D816 V gene mutation. The epigenetic mechanism has also been suggested as playing a role in mastocytosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Based on our previous epigenetic studies, we have selected 110 candidate genes which were sequenced by next generation sequencing (NGS) to identify somatic mutations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>The study group consisted of 32 patients with mastocytosis (16 females and 16 males) plus 16 controls (8 females and 8 males). Whole peripheral blood was collected from all the subjects and genotyped by NGS on the Illumina platform (targeted sequencing).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We analysed 4272 genetic variations in the pre-selected candidate genes and found five regions that showed a significant difference between the patient and control group. Two of them were found in the <i>TET2</i> gene located on chromosome 4 and the other three alterations were found in the genes <i>DNMT3A</i>, <i>SETD2</i> and <i>BRD4</i> located on chromosomes 2, 3 and 19, respectively. Two out of the five genetic variants have not been previously reported, despite the fact that all four genes have been described to be associated with mastocytosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results align with our previous findings, which determined <i>TET2</i>, <i>DNMT3A</i>, <i>SETD2</i> and <i>BRD4</i> genes as promising candidates for further analysis, warranting future study in a larger cohort of mastocytosis patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198492","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}
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