Pub Date : 2024-08-06eCollection Date: 2024-01-01DOI: 10.3389/falgy.2024.1361403
Mona I Kidon, Soad Haj Yahia, Gadi Abebe-Campino, Nancy Agmon-Levin, Michal Yelon
Background: Drug hypersensitivity reactions are common in pediatric hemato-oncology patients due to multiple factors including immune compromise and pharmacological complexities. Fever can signify severe delayed-type hypersensitivity reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS). The etiology of fever as an isolated hypersensitivity reaction to chemotherapeutic agents not fully understood. Here, we report three children with intracranial neoplasms experiencing recurrent febrile reactions following Vinca alkaloid-based chemotherapy, mitigated by cysteinyl leukotriene receptor antagonist therapy.
Methods: We present a series of pediatric patients with diverse intracranial neoplasms who developed recurrent fever episodes after multiple courses of Vinca alkaloid-based chemotherapy. Treatment involved prophylactic and post-chemotherapy administration of a cysteinyl leukotriene receptor antagonist to prevent fever episodes and enable completion of chemotherapy regimens without protocol modifications or desensitization.
Results: All three patients experienced fever consistent with delayed-type hypersensitivity reactions to Vinca alkaloids. Prophylactic use of the leukotriene antagonist Montelukast successfully prevented fever recurrence, allowing uninterrupted completion of chemotherapy courses.
Conclusion: Our findings suggest that Montelukast, a leukotriene antagonist, may be beneficial in managing fever as a delayed-type hypersensitivity reaction to Vinca alkaloids in pediatric patients. Further research is warranted to elucidate the underlying mechanisms and leukotriene pathways involved in drug-induced fever reactions.
{"title":"Drug fever-an immune-mediated delayed type hypersensitivity reaction to Vinca alkaloids in pediatric oncology patients, possibly mediated by cysteinyl leukotrienes.","authors":"Mona I Kidon, Soad Haj Yahia, Gadi Abebe-Campino, Nancy Agmon-Levin, Michal Yelon","doi":"10.3389/falgy.2024.1361403","DOIUrl":"10.3389/falgy.2024.1361403","url":null,"abstract":"<p><strong>Background: </strong>Drug hypersensitivity reactions are common in pediatric hemato-oncology patients due to multiple factors including immune compromise and pharmacological complexities. Fever can signify severe delayed-type hypersensitivity reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS). The etiology of fever as an isolated hypersensitivity reaction to chemotherapeutic agents not fully understood. Here, we report three children with intracranial neoplasms experiencing recurrent febrile reactions following Vinca alkaloid-based chemotherapy, mitigated by cysteinyl leukotriene receptor antagonist therapy.</p><p><strong>Methods: </strong>We present a series of pediatric patients with diverse intracranial neoplasms who developed recurrent fever episodes after multiple courses of Vinca alkaloid-based chemotherapy. Treatment involved prophylactic and post-chemotherapy administration of a cysteinyl leukotriene receptor antagonist to prevent fever episodes and enable completion of chemotherapy regimens without protocol modifications or desensitization.</p><p><strong>Results: </strong>All three patients experienced fever consistent with delayed-type hypersensitivity reactions to Vinca alkaloids. Prophylactic use of the leukotriene antagonist Montelukast successfully prevented fever recurrence, allowing uninterrupted completion of chemotherapy courses.</p><p><strong>Conclusion: </strong>Our findings suggest that Montelukast, a leukotriene antagonist, may be beneficial in managing fever as a delayed-type hypersensitivity reaction to Vinca alkaloids in pediatric patients. Further research is warranted to elucidate the underlying mechanisms and leukotriene pathways involved in drug-induced fever reactions.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-02eCollection Date: 2024-01-01DOI: 10.3389/falgy.2024.1423938
Mariem Radhouani, Philipp Starkl
Asthma is a chronic respiratory disease of global importance. Mouse models of allergic asthma have been instrumental in advancing research and novel therapeutic strategies for patients. The application of relevant allergens and physiological routes of exposure in such models has led to valuable insights into the complexities of asthma onset and development as well as key disease mechanisms. Furthermore, environmental microbial exposures and infections have been shown to play a fundamental part in asthma pathogenesis and alter disease outcome. In this review, we delve into physiological mouse models of allergic asthma and explore literature reports on most significant interplays between microbial infections and asthma development with relevance to human disease.
{"title":"Adjuvant-independent airway sensitization and infection mouse models leading to allergic asthma.","authors":"Mariem Radhouani, Philipp Starkl","doi":"10.3389/falgy.2024.1423938","DOIUrl":"10.3389/falgy.2024.1423938","url":null,"abstract":"<p><p>Asthma is a chronic respiratory disease of global importance. Mouse models of allergic asthma have been instrumental in advancing research and novel therapeutic strategies for patients. The application of relevant allergens and physiological routes of exposure in such models has led to valuable insights into the complexities of asthma onset and development as well as key disease mechanisms. Furthermore, environmental microbial exposures and infections have been shown to play a fundamental part in asthma pathogenesis and alter disease outcome. In this review, we delve into physiological mouse models of allergic asthma and explore literature reports on most significant interplays between microbial infections and asthma development with relevance to human disease.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11327155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01eCollection Date: 2024-01-01DOI: 10.3389/falgy.2024.1448007
Tobias Weihrauch, Rossana C N Melo, Natalie Gray, David Voehringer, Peter F Weller, Ulrike Raap
Eosinophil granulocytes, a specialized subset of white blood cells, have traditionally been associated with allergic responses and parasitic infections. However, recent research has unveiled their versatile roles in immune regulation beyond these classical functions. This review highlights the emerging field of eosinophil biology, with a particular focus on their release of extracellular vesicles (EVs) and extracellular DNA traps (EETs). It further explores potential implications of eosinophil-derived EVs and EETs for immune responses during inflammatory diseases. The release of EVs/EETs from eosinophils, which also affects the eosinophils themselves, may influence both local and systemic immune reactions, affecting the pathophysiology of conditions such as airway inflammation, chronic rhinosinusitis and atopic dermatitis.
嗜酸性粒细胞是白细胞的一个特殊亚群,传统上与过敏反应和寄生虫感染有关。然而,最近的研究揭示了嗜酸性粒细胞在这些经典功能之外的免疫调节中的多种作用。这篇综述重点介绍了嗜酸性粒细胞生物学这一新兴领域,尤其关注它们释放的胞外囊泡 (EV) 和胞外 DNA 陷阱 (EET)。它进一步探讨了嗜酸性粒细胞衍生的EVs和EETs对炎症性疾病期间免疫反应的潜在影响。嗜酸性粒细胞释放的 EVs/EETs 也会影响嗜酸性粒细胞本身,可能会影响局部和全身的免疫反应,从而影响气道炎症、慢性鼻炎和特应性皮炎等疾病的病理生理学。
{"title":"Eosinophil extracellular vesicles and DNA traps in allergic inflammation.","authors":"Tobias Weihrauch, Rossana C N Melo, Natalie Gray, David Voehringer, Peter F Weller, Ulrike Raap","doi":"10.3389/falgy.2024.1448007","DOIUrl":"10.3389/falgy.2024.1448007","url":null,"abstract":"<p><p>Eosinophil granulocytes, a specialized subset of white blood cells, have traditionally been associated with allergic responses and parasitic infections. However, recent research has unveiled their versatile roles in immune regulation beyond these classical functions. This review highlights the emerging field of eosinophil biology, with a particular focus on their release of extracellular vesicles (EVs) and extracellular DNA traps (EETs). It further explores potential implications of eosinophil-derived EVs and EETs for immune responses during inflammatory diseases. The release of EVs/EETs from eosinophils, which also affects the eosinophils themselves, may influence both local and systemic immune reactions, affecting the pathophysiology of conditions such as airway inflammation, chronic rhinosinusitis and atopic dermatitis.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-29eCollection Date: 2024-01-01DOI: 10.3389/falgy.2024.1439698
Anatole Hanniet, Marc Puyraveau, Florence Castelain, Fabien Pelletier, François Aubin
Introduction: Various clinical decision-making tools for penicillin allergy have been developed to guide delabeling strategies.
Objective: To evaluate the penicillin allergy PEN-FAST decision score in a retrospective cohort of patients, adults and children, with penicillin-reported allergy.
Methods: This monocentric retrospective cohort included patients with penicillin-reported allergy. All patients underwent penicillin allergy testing using skin tests and/or drug challenge. The PEN-FAST score sensitivity, specificity, negative (NPV) and positive (PPV) predictive values, and the area under the receiver operating characteristics curve (AUC) were calculated.
Results: Two hundred and fourteen patients were included (64 children and 150 adults). Allergy was confirmed in 52 cases (24%). A PEN-FAST score <3 points showed a poor discrimination capacity for the whole population (AUC = 0.66; 95% CI: 0.58-0.75), while it demonstrated a better discrimination capacity in the adults group (AUC = 0.71; 95% CI: 0.63-0.80). The sensitivity to identify penicillin allergy using this cutoff of less than 3 points was 0.67 (95% CI: 0.52-0.80); specificity, 0.58 (95% CI: 0.48-0.68); PPV, 0.43 (95% CI: 0.32-0.55); and NPV, 0.78 (95% CI: 0.68-0.87).
Conclusions: Although our data confirm a rather good discrimination value of a PEN-FAST score <3 points, its low negative predictive value (78%) did not advocate for its use as an accurate, simple and cost-effective clinical decision-making tool to effectively reduce the number of penicillin skin tests required before direct oral challenge. Further studies are required to improve the predictive capacity of the PEN-FAST score.
{"title":"Efficacy of the PEN-FAST score in a French cohort of patients with reported allergy to penicillins.","authors":"Anatole Hanniet, Marc Puyraveau, Florence Castelain, Fabien Pelletier, François Aubin","doi":"10.3389/falgy.2024.1439698","DOIUrl":"10.3389/falgy.2024.1439698","url":null,"abstract":"<p><strong>Introduction: </strong>Various clinical decision-making tools for penicillin allergy have been developed to guide delabeling strategies.</p><p><strong>Objective: </strong>To evaluate the penicillin allergy PEN-FAST decision score in a retrospective cohort of patients, adults and children, with penicillin-reported allergy.</p><p><strong>Methods: </strong>This monocentric retrospective cohort included patients with penicillin-reported allergy. All patients underwent penicillin allergy testing using skin tests and/or drug challenge. The PEN-FAST score sensitivity, specificity, negative (NPV) and positive (PPV) predictive values, and the area under the receiver operating characteristics curve (AUC) were calculated.</p><p><strong>Results: </strong>Two hundred and fourteen patients were included (64 children and 150 adults). Allergy was confirmed in 52 cases (24%). A PEN-FAST score <3 points showed a poor discrimination capacity for the whole population (AUC = 0.66; 95% CI: 0.58-0.75), while it demonstrated a better discrimination capacity in the adults group (AUC = 0.71; 95% CI: 0.63-0.80). The sensitivity to identify penicillin allergy using this cutoff of less than 3 points was 0.67 (95% CI: 0.52-0.80); specificity, 0.58 (95% CI: 0.48-0.68); PPV, 0.43 (95% CI: 0.32-0.55); and NPV, 0.78 (95% CI: 0.68-0.87).</p><p><strong>Conclusions: </strong>Although our data confirm a rather good discrimination value of a PEN-FAST score <3 points, its low negative predictive value (78%) did not advocate for its use as an accurate, simple and cost-effective clinical decision-making tool to effectively reduce the number of penicillin skin tests required before direct oral challenge. Further studies are required to improve the predictive capacity of the PEN-FAST score.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-18DOI: 10.3389/falgy.2024.1427279
Oscar Palomares, Carolina Cisneros, Francisco Javier Ortiz de Frutos, J. M. Villacampa, Ignacio Dávila
Dysregulation of type 2 (T2) immune response leads to an aberrant inflammatory reaction that constitutes the pathophysiological basis of diseases involving various organs. For this reason, several disorders can coexist in a single patient; however, as different specialists often treat these pathologies, T2 dysregulation, particularly when mild, is not always the first diagnostic suspicion. A breakdown in interdisciplinary communication or the lack of adequate tools to detect these entities can delay diagnosis, and this, together with a lack of coordination, can lead to suboptimal care. In this context, a multidisciplinary group of specialists in pneumology, immunology, allergology, dermatology and otorhinolaryngology compiled a list of the cardinal symptoms reported by patients presenting with T2 inflammation-related diseases: asthma, chronic rhinosinusitis, allergic rhinitis, allergic conjunctivitis, IgE-mediated food allergy, atopic dermatitis, eosinophilic oesophagitis, and NSAID-exacerbated respiratory disease (NERD). Using this information, we propose a simple, patient-friendly questionnaire that can be administered at any level of care to initially screen patients for suspected coexisting T2 diseases and referral to the appropriate specialist.
{"title":"Multidisciplinary management of type 2 inflammation diseases using a screening tool","authors":"Oscar Palomares, Carolina Cisneros, Francisco Javier Ortiz de Frutos, J. M. Villacampa, Ignacio Dávila","doi":"10.3389/falgy.2024.1427279","DOIUrl":"https://doi.org/10.3389/falgy.2024.1427279","url":null,"abstract":"Dysregulation of type 2 (T2) immune response leads to an aberrant inflammatory reaction that constitutes the pathophysiological basis of diseases involving various organs. For this reason, several disorders can coexist in a single patient; however, as different specialists often treat these pathologies, T2 dysregulation, particularly when mild, is not always the first diagnostic suspicion. A breakdown in interdisciplinary communication or the lack of adequate tools to detect these entities can delay diagnosis, and this, together with a lack of coordination, can lead to suboptimal care. In this context, a multidisciplinary group of specialists in pneumology, immunology, allergology, dermatology and otorhinolaryngology compiled a list of the cardinal symptoms reported by patients presenting with T2 inflammation-related diseases: asthma, chronic rhinosinusitis, allergic rhinitis, allergic conjunctivitis, IgE-mediated food allergy, atopic dermatitis, eosinophilic oesophagitis, and NSAID-exacerbated respiratory disease (NERD). Using this information, we propose a simple, patient-friendly questionnaire that can be administered at any level of care to initially screen patients for suspected coexisting T2 diseases and referral to the appropriate specialist.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141824438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-18DOI: 10.3389/falgy.2024.1440478
Scott McClain, Gregory Ladics
{"title":"Editorial: What have we learned over the last 25 years assessing novel food and protein allergenicity","authors":"Scott McClain, Gregory Ladics","doi":"10.3389/falgy.2024.1440478","DOIUrl":"https://doi.org/10.3389/falgy.2024.1440478","url":null,"abstract":"","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141827970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-18DOI: 10.3389/falgy.2024.1459032
Davor Plavec, C. Andaloro, Giorgio Ciprandi, I. La Mantia, Cesare Miani, A. Varricchio
{"title":"Editorial: A contemporary look at allergic rhinitis treatments: where are we heading?","authors":"Davor Plavec, C. Andaloro, Giorgio Ciprandi, I. La Mantia, Cesare Miani, A. Varricchio","doi":"10.3389/falgy.2024.1459032","DOIUrl":"https://doi.org/10.3389/falgy.2024.1459032","url":null,"abstract":"","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141826553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-17DOI: 10.3389/falgy.2024.1439303
Anna-Lena Pirker, Thomas Vogl
The early microbial colonization of human mucosal surfaces is essential for the development of the host immune system. Already during pregnancy, the unborn child is prepared for the postnatal influx of commensals and pathogens via maternal antibodies, and after birth this protection is continued with antibodies in breast milk. During this critical window of time, which extends from pregnancy to the first year of life, each encounter with a microorganism can influence children's immune response and can have a lifelong impact on their life. For example, there are numerous links between the development of allergies and an altered gut microbiome. However, the exact mechanisms behind microbial influences, also extending to how viruses influence host-microbe interactions, are incompletely understood. In this review, we address the impact of infants’ first microbial encounters, how the immune system develops to interact with gut microbiota, and summarize how an altered immune response could be implied in allergies.
{"title":"Development of systemic and mucosal immune responses against gut microbiota in early life and implications for the onset of allergies","authors":"Anna-Lena Pirker, Thomas Vogl","doi":"10.3389/falgy.2024.1439303","DOIUrl":"https://doi.org/10.3389/falgy.2024.1439303","url":null,"abstract":"The early microbial colonization of human mucosal surfaces is essential for the development of the host immune system. Already during pregnancy, the unborn child is prepared for the postnatal influx of commensals and pathogens via maternal antibodies, and after birth this protection is continued with antibodies in breast milk. During this critical window of time, which extends from pregnancy to the first year of life, each encounter with a microorganism can influence children's immune response and can have a lifelong impact on their life. For example, there are numerous links between the development of allergies and an altered gut microbiome. However, the exact mechanisms behind microbial influences, also extending to how viruses influence host-microbe interactions, are incompletely understood. In this review, we address the impact of infants’ first microbial encounters, how the immune system develops to interact with gut microbiota, and summarize how an altered immune response could be implied in allergies.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141829282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.3389/falgy.2024.1417879
Ronald L. Rabin, Derek Croote, Aaron Chen, E. Dobrovolskaia, Joyce Jia Wen Wong, Jessica Grossman, Robert G. Hamilton
In the United States, 19 allergen extracts of different specificities are standardized, which means that their potencies are determined in comparison to a US reference standard. For cat allergen extracts, potency is determined by measuring Fel d 1 content expressed in in Fel d 1 units, and with a unitage that correlates with skin test reactions (bioequivalent allergy units or BAU). Currently, Fel d 1 content is measured with a radial immunodiffusion (RID) assay that uses polyclonal sheep antisera to detect the allergenic protein by producing a white precipitin line in agar gel. However, the RID is considered cumbersome, and the polyclonal sera may qualitatively vary among animals and may recognize epitopes irrelevant to human allergic disease. In this report, we describe a quantitative two-site immunoenzymetric assay (IEMA) for Fel d 1 that uses immobilized capture and soluble biotin-labeled detection Fel d 1-specific human IgE monoclonal antibodies (mAb) that have been class-switched to IgG4. Together, they sandwich Fel d 1 molecules from extracts. Using purified natural Fel d 1 as a calibrator, the historically reported ∼4 micrograms Fel d 1/Fel d 1 unit assignment was directly measured in this mAb-based IEMA at 3.12 ± 0.24 micrograms of Fel d 1 per Fel d 1 unit. This IEMA appears to be equivalent to RID in the measurement of biological potencies of commercial cat hair and cat pelt extracts marketed in the United States.
在美国,有 19 种不同特异性的过敏原提取物被标准化,这意味着它们的效价是根据与美国参考标准的比较来确定的。对于猫过敏原提取物,其效价是通过测量 Fel d 1 含量(以 Fel d 1 单位表示)和与皮试反应相关的单位(生物等效过敏单位或 BAU)来确定的。目前,Fel d 1 含量是通过径向免疫扩散(RID)测定法来测量的,该方法使用多克隆羊抗血清,通过在琼脂凝胶中产生白色沉淀线来检测过敏原蛋白。然而,放射免疫扩散法操作繁琐,而且不同动物的多克隆血清可能存在定性差异,并可能识别与人类过敏性疾病无关的表位。在本报告中,我们介绍了一种针对 Fel d 1 的定量双位点免疫酶测定法(IEMA),它使用固定捕获和可溶性生物素标记的 Fel d 1 特异性人类 IgE 单克隆抗体(mAb)进行检测,这些抗体已被分级为 IgG4。它们共同夹住了提取物中的 Fel d 1 分子。使用纯化的天然 Fel d 1 作为校准物,在这种基于 mAb 的 IEMA 中直接测得每 Fel d 1 单位的 Fel d 1 含量为 3.12 ± 0.24 微克,即历史上报道的 Fel d 1 含量为 4 微克/Fel d 1 单位。在测量美国市场上销售的商品猫毛和猫皮提取物的生物效力时,这种 IEMA 似乎等同于 RID。
{"title":"A human monoclonal antibody based immunoenzymetric assay to measure Fel d 1 concentrations in cat hair and pelt allergenic extracts","authors":"Ronald L. Rabin, Derek Croote, Aaron Chen, E. Dobrovolskaia, Joyce Jia Wen Wong, Jessica Grossman, Robert G. Hamilton","doi":"10.3389/falgy.2024.1417879","DOIUrl":"https://doi.org/10.3389/falgy.2024.1417879","url":null,"abstract":"In the United States, 19 allergen extracts of different specificities are standardized, which means that their potencies are determined in comparison to a US reference standard. For cat allergen extracts, potency is determined by measuring Fel d 1 content expressed in in Fel d 1 units, and with a unitage that correlates with skin test reactions (bioequivalent allergy units or BAU). Currently, Fel d 1 content is measured with a radial immunodiffusion (RID) assay that uses polyclonal sheep antisera to detect the allergenic protein by producing a white precipitin line in agar gel. However, the RID is considered cumbersome, and the polyclonal sera may qualitatively vary among animals and may recognize epitopes irrelevant to human allergic disease. In this report, we describe a quantitative two-site immunoenzymetric assay (IEMA) for Fel d 1 that uses immobilized capture and soluble biotin-labeled detection Fel d 1-specific human IgE monoclonal antibodies (mAb) that have been class-switched to IgG4. Together, they sandwich Fel d 1 molecules from extracts. Using purified natural Fel d 1 as a calibrator, the historically reported ∼4 micrograms Fel d 1/Fel d 1 unit assignment was directly measured in this mAb-based IEMA at 3.12 ± 0.24 micrograms of Fel d 1 per Fel d 1 unit. This IEMA appears to be equivalent to RID in the measurement of biological potencies of commercial cat hair and cat pelt extracts marketed in the United States.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141649397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.3389/falgy.2024.1418922
Graham Roberts, E. Valovirta, S. Halken, Peter A. Eng, Mika J. Mäkelä, K. L. Lødrup Carlsen, Roland Knecht, L. P. Malmberg
Asthma is a common chronic disease in children. It is a dynamic condition—symptoms change over time, and the outcome of diagnostic tests can vary. Consequently, evaluating the onset of asthma at a single point in time, perhaps when patients are asymptomatic with limited impairment of the lung function, may result in false diagnostic conclusions. The absence of consistent gold-standard diagnostic criteria in children challenges the ability of any study to ascertain an effect of treatment on asthma prevention. A comprehensive review of the diagnostic criteria used for new-onset asthma in school-age children was conducted based on existing recommendations from published clinical guidance, alongside evidence from paediatric asthma prevention trials. Findings from the review were used to propose suggestions for diagnosing new-onset asthma in future asthma prevention trials. Despite an overall lack of consensus in the published clinical guidance, there are similarities between the various recommendations for diagnosing asthma in children, which typically involve assessing the variable symptoms and supplementing the medical history with objective measures of lung function. For future paediatric asthma prevention trials, we suggest that paediatric clinical trials should use a new-onset asthma definition that incorporates the concepts of “possible”, “probable” and “confirmed” asthma. “Possible” asthma would capture self-reported features of chronic symptoms and symptom relief with β2-agonist bronchodilator (suggesting reversibility). “Probable” asthma would include symptom chronicity, self-reported symptom relief with β2-agonist bronchodilator, and objective features of asthma (reversibility or bronchial hyper-responsiveness). A “confirmed” diagnosis would be made only if there is a positive response to controller therapy. These suggestions aim to improve the diagnosis of new-onset childhood asthma in clinical trials, which will be useful in the design and conduct of future paediatric asthma prevention trials.
{"title":"Diagnosing new-onset asthma in a paediatric clinical trial setting in school-age children","authors":"Graham Roberts, E. Valovirta, S. Halken, Peter A. Eng, Mika J. Mäkelä, K. L. Lødrup Carlsen, Roland Knecht, L. P. Malmberg","doi":"10.3389/falgy.2024.1418922","DOIUrl":"https://doi.org/10.3389/falgy.2024.1418922","url":null,"abstract":"Asthma is a common chronic disease in children. It is a dynamic condition—symptoms change over time, and the outcome of diagnostic tests can vary. Consequently, evaluating the onset of asthma at a single point in time, perhaps when patients are asymptomatic with limited impairment of the lung function, may result in false diagnostic conclusions. The absence of consistent gold-standard diagnostic criteria in children challenges the ability of any study to ascertain an effect of treatment on asthma prevention. A comprehensive review of the diagnostic criteria used for new-onset asthma in school-age children was conducted based on existing recommendations from published clinical guidance, alongside evidence from paediatric asthma prevention trials. Findings from the review were used to propose suggestions for diagnosing new-onset asthma in future asthma prevention trials. Despite an overall lack of consensus in the published clinical guidance, there are similarities between the various recommendations for diagnosing asthma in children, which typically involve assessing the variable symptoms and supplementing the medical history with objective measures of lung function. For future paediatric asthma prevention trials, we suggest that paediatric clinical trials should use a new-onset asthma definition that incorporates the concepts of “possible”, “probable” and “confirmed” asthma. “Possible” asthma would capture self-reported features of chronic symptoms and symptom relief with β2-agonist bronchodilator (suggesting reversibility). “Probable” asthma would include symptom chronicity, self-reported symptom relief with β2-agonist bronchodilator, and objective features of asthma (reversibility or bronchial hyper-responsiveness). A “confirmed” diagnosis would be made only if there is a positive response to controller therapy. These suggestions aim to improve the diagnosis of new-onset childhood asthma in clinical trials, which will be useful in the design and conduct of future paediatric asthma prevention trials.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141648703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}