Frontiers in allergyPub Date : 2025-04-30eCollection Date: 2025-01-01DOI: 10.3389/falgy.2025.1576816
Jelena Pesic, Juan José Nieto-Fontarigo, Katerina Pardali, Stephen Delaney, Henric Olsson, Lena Uller
{"title":"T2 cytokine-driven alarmin and antiviral responses in asthma: insights into immune modulation and the role of IL-4Rα targeting.","authors":"Jelena Pesic, Juan José Nieto-Fontarigo, Katerina Pardali, Stephen Delaney, Henric Olsson, Lena Uller","doi":"10.3389/falgy.2025.1576816","DOIUrl":"https://doi.org/10.3389/falgy.2025.1576816","url":null,"abstract":"<p><strong>Introduction: </strong>Severe asthma is a heterogeneous condition characterized by distinct phenotypes and endotypes based on clinical or biological characteristics. Interleukin (IL) 4 and IL-13 are central cytokines in the type 2 (T2) immune response, crucial for T2 inflammation. Biologic therapies targeting the IL-4/IL-13 pathway, such as anti-IL-4Rα monoclonal antibodies (mAbs), have shown improvements in lung function and reductions in exacerbation rates for severe asthma. However, the precise role of early innate immune responses in mediating these therapeutic benefits remains unclear. This study investigates the acute and chronic effects of T2 cytokines on healthy and asthmatic bronchial epithelial cells (BECs), addressing the mechanisms underlying IL-4Rα mAb therapy in acute T2-driven inflammatory conditions and rhinoviral infection in asthma BECs.</p><p><strong>Methods: </strong>Human BECs from healthy and asthma donors were cultured at the air-liquid interface (ALI) and stimulated with IL-4 and IL-13, acutely or chronically, with or without IL-4Rα mAb, followed by rhinovirus (RV) infection. Cells were harvested 24 h post-infection. Expression levels of chemokines, alarmins, and antiviral mediators were quantified using RT-qPCR and multiplex ELISA.</p><p><strong>Results: </strong>CCL26 expression increased in response to IL-4 or IL-13 in healthy and asthmatic BECs, and this effect was significantly more pronounced in asthmatic BECs. IL-4Rα mAb treatment effectively inhibited CCL26 production in BECs from asthma patients. IL-4 and RV infection induced a significant increase in thymic stromal lymphopoietin (TSLP) levels in BECs from asthma compared with healthy, which was normalized by IL-4Rα mAb. No significant effects of T2 cytokines on alarmins were observed in healthy BECs. Chronic exposure to T2 cytokines following RV infection significantly decreased TSLP and IFN<i>λ</i>1 but increased IFNβ, specifically in asthmatic BECs.</p><p><strong>Conclusions: </strong>Our study on T2 cytokines' effects on BECs reveals that asthma BECs have an increased inflammatory response to IL-4 and IL-13. These responses, marked by increased CCL26 and TSLP, were effectively mitigated by IL-4Rα mAb. Importantly, this treatment maintained essential antiviral defenses, such as IFNβ, even post-rhinoviral infection. Our results suggest a novel mechanism by which IL-4Rα mAb controls exacerbations and improves lung function.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1576816"},"PeriodicalIF":3.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082527","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}
Frontiers in allergyPub Date : 2025-04-30eCollection Date: 2025-01-01DOI: 10.3389/falgy.2025.1584928
D J Adamko, Kyla J Hildebrand
{"title":"The changing epidemiology of paediatric childhood asthma and allergy in different regions of the world.","authors":"D J Adamko, Kyla J Hildebrand","doi":"10.3389/falgy.2025.1584928","DOIUrl":"https://doi.org/10.3389/falgy.2025.1584928","url":null,"abstract":"<p><p>Allergic disorders encompass a variety of conditions including asthma, atopic dermatitis, food allergy, allergic rhinitis, and eosinophilic esophagitis. These atopic disorders are connected via an abnormal host immune response to the environment. A series of longitudinal cross-sectional studies conducted over the past 3 decades have reported on the epidemiological trends that contribute towards the development of pediatric asthma and allergic disease. Infant birth cohort studies assessing the microbiome have offered clues as to the underlying biological mechanisms and basis for allergic disease. Why this abnormal immune response is occurring is the basis of decades of research and the reasons for this chapter. Our understanding of the biology of the immune system has increased exponentially with the advances in genomic testing, providing further opportunity for targeted treatments and more importantly, primary prevention of atopic disease.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1584928"},"PeriodicalIF":3.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082535","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}
Frontiers in allergyPub Date : 2025-04-29eCollection Date: 2025-01-01DOI: 10.3389/falgy.2025.1554940
Wenjin Du, Ke Yang, Qiuxing Zhang, Xianghua Lin, Wenchao Zhang, Weili Guo, Zhaoji Meng, Siqin Wang
{"title":"Case Report: Identification of a novel mutation, c.1067T > A, in the <i>SERPING1</i> gene in a Chinese male with type 1 hereditary angioedema.","authors":"Wenjin Du, Ke Yang, Qiuxing Zhang, Xianghua Lin, Wenchao Zhang, Weili Guo, Zhaoji Meng, Siqin Wang","doi":"10.3389/falgy.2025.1554940","DOIUrl":"10.3389/falgy.2025.1554940","url":null,"abstract":"<p><p>Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder characterized by recurrent, unpredictable episodes of angioedema that commonly involve the face, limbs, respiratory tract, and gastrointestinal tract. Clinical presentations vary substantially among individuals, increasing the likelihood of misdiagnosis or missed diagnosis. In severe cases, if not properly managed, laryngeal edema can result in asphyxiation or even death. Here, we report a Chinese male patient who experienced recurrent limb swelling and abdominal pain. Laboratory tests revealed low levels of complement C4 and C1 inhibitors, along with impaired C1 inhibitor function. Genomic DNA extracted from peripheral blood samples underwent PCR amplification and Sanger sequencing, which identified a <i>de novo</i> heterozygous mutation in the <i>SERPING1</i> gene at chr11:57379227, confirming a novel missense mutation NM_000062.c.1067T > A (p.V356E). Ultimately, the patient was diagnosed with HAE-C1INH-Type1 and successfully protected from recurrent attacks through subcutaneous administration of lanadelumab.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1554940"},"PeriodicalIF":3.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993319","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}
Frontiers in allergyPub Date : 2025-04-28eCollection Date: 2025-01-01DOI: 10.3389/falgy.2025.1608998
Jennifer L P Protudjer, Lucy A Bilaver
{"title":"Editorial: The socio-economic burden of food allergy: from households to healthcare systems.","authors":"Jennifer L P Protudjer, Lucy A Bilaver","doi":"10.3389/falgy.2025.1608998","DOIUrl":"https://doi.org/10.3389/falgy.2025.1608998","url":null,"abstract":"","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1608998"},"PeriodicalIF":3.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054665","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}
Frontiers in allergyPub Date : 2025-04-25eCollection Date: 2025-01-01DOI: 10.3389/falgy.2025.1608925
{"title":"Erratum: A novel assay of excess plasma kallikrein-kinin system activation in hereditary angioedema.","authors":"","doi":"10.3389/falgy.2025.1608925","DOIUrl":"https://doi.org/10.3389/falgy.2025.1608925","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/falgy.2024.1436855.].</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1608925"},"PeriodicalIF":3.3,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058038","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}
{"title":"Tissue eosinophil level as a predictor of control, severity, and recurrence of Chronic Rhinosinusitis with Nasal Polyps.","authors":"Julissa Vizcarra-Melgar, Serafín Sánchez-Gómez, Nuria López-González, Ramón Moreno-Luna, Jaime González-García, Juan Maza-Solano","doi":"10.3389/falgy.2025.1549332","DOIUrl":"https://doi.org/10.3389/falgy.2025.1549332","url":null,"abstract":"<p><strong>Introduction: </strong>The histopathologic study of nasal polyps establishes endotype features of chronic rhinosinusitis (CRS). A tissular eosinophil count greater than 10 per high power field (HPF) classifies this condition as type 2 inflammation. Blood and mucosal eosinophils are suggested as biomarkers of severity and control of CRS. Additionally, a tissular eosinophil count greater than 55 per HPF has been related to a high risk of recurrence in the Asian population. Our study aims to determine whether tissue eosinophil count is associated with the control, severity, and recurrence of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP).</p><p><strong>Methods: </strong>An observational study of patients with CRSwNP who underwent nasal mucosa biopsy was conducted between June 2021 and November 2023. Histopathologic features, asthma control, CRSwNP control and severity according to the POLINA consensus, quality of life parameters, recurrence of CRSwNP, and laboratory markers were recorded and compared with the tissular eosinophil count.</p><p><strong>Results: </strong>A total of 108 cases were included. The majority (70.4%) had concomitant asthma, with 31.5% of the cases having well-controlled disease. Most patients had uncontrolled (57.4%) and severe (62%) CRSwNP. Fifty-four cases underwent surgery and 43.5% experienced recurrence. More than half had a SNOT-22 score greater than 50 points. Eighty-one percent of patients had a tissular eosinophil count greater than 10 per HPF, and 60.2% had blood eosinophilia greater than <math><mn>0.3</mn> <mo>×</mo> <msup><mn>10</mn> <mn>3</mn></msup> </math> . Blood eosinophilia was related to CRSwNP severity and control. No significant differences were found between tissue eosinophil count and the severity, control, and recurrence of CRSwNP.</p><p><strong>Conclusion: </strong>Tissue eosinophil levels were not a marker of control, severity, and recurrence of CRSwNP in our data. Blood eosinophil levels, however, were a marker of CRSwNP control and severity.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1549332"},"PeriodicalIF":3.3,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058040","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}
Frontiers in allergyPub Date : 2025-04-24eCollection Date: 2025-01-01DOI: 10.3389/falgy.2025.1547225
Lizette M Cortes, Nelson R Vinueza
{"title":"Impaired cell viability and mitochondrial respiration by disperse textile dyes.","authors":"Lizette M Cortes, Nelson R Vinueza","doi":"10.3389/falgy.2025.1547225","DOIUrl":"https://doi.org/10.3389/falgy.2025.1547225","url":null,"abstract":"<p><p>In recent years, the use of synthetic textile dyes has increased. The effects of these chemicals or their metabolites on our skin and our immune system have not been well studied. However, skin irritants have been reported to break the dermal barrier to start a chain of reactions that dysregulate the immune system. In the last decades, the incidence of atopic diseases and cancer has been increasing. There is an urgent need to identify the environmental triggers that fuel these conditions. This study aimed to investigate the effects of some of the common disperse textile dyes on the viability, and mitochondrial function of cultures of mouse keratinocytes (MPEK-BL6 line) and intestinal porcine epithelial cells (IPEC-J2 cells). The cells were cultured with Disperse (D) dyes Red 11, Orange 37, Blue 1, Blue 124, Blue 291, Blue 79.1, and Brown 1 as well as Quinone and Tartrazine, and PPD as control. At concentrations representative of human exposure from 30 min to 3 days. Cell viability, Oxygen Consumption Rate (OCR) and Extracellular Acidification Rate (ECAR) were quantified. Disperse Blue 1, Blue 124, and Brown 1 impaired cell viability and mitochondrial function as early as 3 h after exposure with IPEC-J2 and MPEK-BL6 cells. However, D. Blue 79.1 and Blue 291 did not have those effects. These data suggest that common disperse textile dyes can influence cell viability and mitochondrial function. This effect could be related to their chemical structure and physicochemical properties, such as size and polarity giving them differences in membrane permeability.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1547225"},"PeriodicalIF":3.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059234","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}
Frontiers in allergyPub Date : 2025-04-24eCollection Date: 2025-01-01DOI: 10.3389/falgy.2025.1601916
Gemma Carreras-Badosa, Vanesa Esteban, Vivian Hernandez-Trujillo, Elina Toskala, Manali Mukherjee, Saba Al Heialy, Karin Fieten
{"title":"Editorial: Women in science: allergy research.","authors":"Gemma Carreras-Badosa, Vanesa Esteban, Vivian Hernandez-Trujillo, Elina Toskala, Manali Mukherjee, Saba Al Heialy, Karin Fieten","doi":"10.3389/falgy.2025.1601916","DOIUrl":"https://doi.org/10.3389/falgy.2025.1601916","url":null,"abstract":"","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1601916"},"PeriodicalIF":3.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055326","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}
{"title":"Case Report: An unusual case of cardiac anaphylaxis in the maintenance phase of <i>vespula</i> venom immunotherapy.","authors":"Silvia Brunetto, Federica Buta, Sebastiano Gangemi, Luisa Ricciardi","doi":"10.3389/falgy.2025.1583909","DOIUrl":"https://doi.org/10.3389/falgy.2025.1583909","url":null,"abstract":"<p><strong>Background: </strong>Cardiac involvement in anaphylaxis remains difficult to assess; however, histamine release during an anaphylactic reaction can induce functional and metabolic alterations in the myocardium. Mast cells, identified within myocardial fibers, perivascular tissue, and arterial structures, play a crucial role in systemic and cardiac anaphylaxis through the release of inflammatory mediators, including histamine, platelet-activating factor, cytokines, chemokines, tryptase, chymase, prostaglandins, and leukotrienes. Hymenoptera venom immunotherapy (VIT) is the most effective strategy for preventing systemic reactions in sensitized individuals. Although VIT is generally well tolerated, severe allergic reactions can occur, particularly during the build-up phase, while they are rare in the maintenance phase.</p><p><strong>Case report: </strong>We present the case of a 57-year-old male with a history of severe systemic reactions (SSR) to Vespula stings who experienced cardiac anaphylaxis during the maintenance phase of VIT. He started VIT with a conventional up-dosing schedule, which was well-tolerated. However, during the third monthly maintenance dose, he developed an anaphylactic syncopal episode with a right bundle branch block (RBBB) on ECG. He was treated promptly with adrenaline, corticosteroids, and antihistamines, and his ECG normalized within 20 days.</p><p><strong>Conclusions: </strong>This case underscores the potential cardiac involvement in anaphylaxis during VIT maintenance and highlights the need to systematically evaluate cardiovascular manifestations during anaphylaxis episodes to optimize risk assessment and management.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1583909"},"PeriodicalIF":3.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044299","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}
Frontiers in allergyPub Date : 2025-04-17eCollection Date: 2025-01-01DOI: 10.3389/falgy.2025.1564564
Yasmina Ouerdani, Imen Zamali, Yousr Galai, Ahlem Ben Hmid, Yosra Nasri, Ines Ben Sghaier, Hayet Kebaier, Hechmi Louzir, Jihene Bouguila, Nissaf Ben Alaya Bouafif, Mélika Ben Ahmed, Samar Samoud
{"title":"Molecular allergen sensitization profile and casein threshold determination predicting the persistence of cow's milk protein allergy in Tunisia (North Africa).","authors":"Yasmina Ouerdani, Imen Zamali, Yousr Galai, Ahlem Ben Hmid, Yosra Nasri, Ines Ben Sghaier, Hayet Kebaier, Hechmi Louzir, Jihene Bouguila, Nissaf Ben Alaya Bouafif, Mélika Ben Ahmed, Samar Samoud","doi":"10.3389/falgy.2025.1564564","DOIUrl":"https://doi.org/10.3389/falgy.2025.1564564","url":null,"abstract":"<p><strong>Background: </strong>Cow's milk protein allergy (CMPA) represents a major health concern in Tunisia, with diagnostic challenges influencing disease prognosis. Molecular allergen testing has emerged as a valuable tool to enhance diagnostic accuracy and predict disease persistence.</p><p><strong>Objective: </strong>This study aims to characterize the clinical and epidemiological features of CMPA in a Tunisian population, with a particular focus on the role of molecular allergens in assessing disease chronicity.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 262 cases of IgE-mediated CMPA diagnosed at the Pasteur Institute of Tunis between 2020 and 2023. Sensitization to molecular allergens was assessed using ImmunoCAP (Phadia 100).</p><p><strong>Results: </strong>CMPA symptoms predominantly manifested in infancy (94%, 246/262), with a male predominance (sex ratio: 1.6). Acute reactions were the most frequent presentation (69.9%, 79/113), and polysensitization was common (81%, 212/262), particularly to β-lactoglobulin. Spontaneous resolution occurred in approximately 33% of cases (29/87), with a mean age of 3 years and 8 months. Persistent CMPA was significantly associated with elevated IgE levels to whole milk, β-lactoglobulin, and casein (<i>p</i> < 0.05). ROC curve analysis identified predictive thresholds for disease persistence, including 4.2 kU/L for whole milk-specific IgE and 0.37 kU/L for casein-specific IgE (<i>p</i> = 0.006).</p><p><strong>Conclusion: </strong>Molecular allergen testing improves CMPA diagnosis and offers critical prognostic insights. The identification of IgE thresholds may facilitate early risk stratification and guide personalized management strategies.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":"6 ","pages":"1564564"},"PeriodicalIF":3.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013750","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}