Jobst Augustin, Stefan Gilge, Heike Appel, Ute Dauert, Christina Endler, Ruth Heesen, Conny Höflich, Wilhelm Kuttler, Katharina Heinke Schlünzen, Wolfgang Straff, Barbora Werchan, Matthias Werchan, Torsten Zuberbier, Claudia Traidl‐Hoffmann
Allergies are one of the major health challenges of our time, associated with a high individual burden of disease and high costs for the healthcare system. Given their prevalence, allergies are also highly relevant from a public health perspective. The development of allergic diseases is multifactorial. In addition to individual factors (e.g., genetic predisposition), environmental factors are particularly important. These include climate (including climate change), weather, and air pollution, which affect the biosphere and biodiversity. Pollen‐associated allergic rhinitis is one of the most common allergies. Airborne pollen is strongly connected with climate (change) and air pollution. For example, interannual climate variability and climate change affect phenology, pollen production, and pollen transport, and air pollutants affect pollen allergenicity. Climate change also affects air quality as meteorological conditions influence relevant processes such as the emission, transport, chemistry, and deposition of air pollutants, which affect the occurrence, intensity, and duration of allergy symptoms. The aims of this position paper are: (a) to provide an overview of the current state of scientific knowledge on the effects of climate change and air quality on pollen allergies, (b) to discuss conflicting objectives in the fight against pollen allergies, and (c) to provide recommendations for policy makers, health professionals, public health measures, and future research.
{"title":"Climate Change, Air Quality, and Pollen Allergies—State of the Art and Recommendations for Research and Public Health","authors":"Jobst Augustin, Stefan Gilge, Heike Appel, Ute Dauert, Christina Endler, Ruth Heesen, Conny Höflich, Wilhelm Kuttler, Katharina Heinke Schlünzen, Wolfgang Straff, Barbora Werchan, Matthias Werchan, Torsten Zuberbier, Claudia Traidl‐Hoffmann","doi":"10.1111/all.70159","DOIUrl":"https://doi.org/10.1111/all.70159","url":null,"abstract":"Allergies are one of the major health challenges of our time, associated with a high individual burden of disease and high costs for the healthcare system. Given their prevalence, allergies are also highly relevant from a public health perspective. The development of allergic diseases is multifactorial. In addition to individual factors (e.g., genetic predisposition), environmental factors are particularly important. These include climate (including climate change), weather, and air pollution, which affect the biosphere and biodiversity. Pollen‐associated allergic rhinitis is one of the most common allergies. Airborne pollen is strongly connected with climate (change) and air pollution. For example, interannual climate variability and climate change affect phenology, pollen production, and pollen transport, and air pollutants affect pollen allergenicity. Climate change also affects air quality as meteorological conditions influence relevant processes such as the emission, transport, chemistry, and deposition of air pollutants, which affect the occurrence, intensity, and duration of allergy symptoms. The aims of this position paper are: (a) to provide an overview of the current state of scientific knowledge on the effects of climate change and air quality on pollen allergies, (b) to discuss conflicting objectives in the fight against pollen allergies, and (c) to provide recommendations for policy makers, health professionals, public health measures, and future research.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"233 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SuJin Hwang, Telly Sepahpour, Stephanie Kortchak, Kirthiram Krishnaveni Sivakumar, Spyros Karaiskos, Ngoc Pham, Yura Jang, Montserrat Puig, Michael Norcross
Background Abacavir (ABC)‐induced hypersensitivity is associated with HLA‐B*57:01, with tolerance maintained by regulatory T cells (Treg). This study hypothesized that the balance between Treg and CD8 + T‐cells is influenced by the level of human leucocyte antigen (HLA) expression to determine hypersensitivity versus tolerance to abacavir. Methods HLA‐B*57:01 transgenic (Tg) mice and Tg mice lacking H2‐K b D b (Tg/KO) were treated with ABC with or without IFN‐α or IFN‐γ blockade. Immune cell phenotype and functions were assessed via flow cytometry, and splenic transcriptomic profiles were analyzed to evaluate gene expression changes associated with treatment. Results ABC treatment of Tg/KO mice, which only express HLA‐B*57:01 as an MHC‐I allele, led to the expansion of drug‐specific CD8 + T‐cells, enhanced antigen presenting cell (APC) activity, and reduction in Tregs. These changes were accompanied by increased IFN‐α levels and plasmacytoid dendritic cell (pDC) maturation. Depletion of pDCs or blocking of IFN‐αR, in contrast to IFN‐γ blockade, restored Treg populations and diminished CD8 + T‐cell responses. These findings demonstrate that IFN‐α, primarily produced by pDCs, disrupts Treg expansion, whereas IFN‐γ predominantly enhances APC maturation and activation. Transcriptomic analysis revealed key genes regulated exclusively by ABC treatment in the presence of both IFN‐α and IFN‐γ signaling and demonstrated that IFN‐α signaling predominantly modulates innate and adaptive immune genes while supporting the downregulation of Treg‐related genes. Conclusions In vivo upregulation of HLA expression modulates the balance between drug‐specific and regulatory T cells, thereby promoting optimal pDC expansion and enhancing IFN‐α production, which counteracts Treg‐mediated ABC tolerance. IFN‐γ secretion by drug‐specific CD8 + T‐cells promoted APC and effector T‐cell function that led to the development of ABC‐associated hypersensitivity reactions in immunocompetent HLA Tg mice.
Abacavir （ABC）诱导的超敏反应与HLA - B*57:01相关，并由调节性T细胞（Treg）维持耐受性。本研究假设Treg和CD8 + T细胞之间的平衡受人白细胞抗原（HLA）表达水平的影响，从而决定对阿巴卡韦的过敏与耐受。方法HLA - B*57:01转基因（Tg）小鼠和缺乏H2 - K B D B （Tg/KO）的Tg小鼠分别用ABC分别阻断或不阻断IFN‐α或IFN‐γ。通过流式细胞术评估免疫细胞表型和功能，并分析脾脏转录组谱以评估与治疗相关的基因表达变化。结果只表达HLA - B*57:01作为MHC - I等位基因的Tg/KO小鼠，ABC处理导致药物特异性CD8 + T细胞扩增，抗原呈递细胞（APC）活性增强，Tregs减少。这些变化伴随着IFN - α水平的升高和浆细胞样树突状细胞（pDC）的成熟。与IFN - γ阻断相比，缺失pDCs或阻断IFN - αR可恢复Treg种群并降低CD8 + T细胞应答。这些发现表明，主要由pDCs产生的IFN‐α破坏Treg的扩增，而IFN‐γ主要促进APC的成熟和激活。转录组学分析显示，在IFN‐α和IFN‐γ信号同时存在的情况下，ABC处理只调控关键基因，并证明IFN‐α信号主要调节先天和适应性免疫基因，同时支持Treg相关基因的下调。结论体内HLA表达上调可调节药物特异性T细胞和调节性T细胞之间的平衡，从而促进最佳pDC扩增和增强IFN α的产生，从而抵消Treg介导的ABC耐受性。药物特异性CD8 + T细胞分泌IFN - γ促进APC和效应T细胞功能，导致免疫功能正常的HLA - Tg小鼠发生ABC相关的超敏反应。
{"title":"Type I and II Interferons Drive Abacavir Hypersensitivity via Treg Suppression and T‐Cell Enhancement in Immunocompetent HLA ‐Transgenic Mice","authors":"SuJin Hwang, Telly Sepahpour, Stephanie Kortchak, Kirthiram Krishnaveni Sivakumar, Spyros Karaiskos, Ngoc Pham, Yura Jang, Montserrat Puig, Michael Norcross","doi":"10.1111/all.70189","DOIUrl":"https://doi.org/10.1111/all.70189","url":null,"abstract":"Background Abacavir (ABC)‐induced hypersensitivity is associated with HLA‐B*57:01, with tolerance maintained by regulatory T cells (Treg). This study hypothesized that the balance between Treg and CD8 <jats:sup>+</jats:sup> T‐cells is influenced by the level of human leucocyte antigen (HLA) expression to determine hypersensitivity versus tolerance to abacavir. Methods HLA‐B*57:01 transgenic (Tg) mice and Tg mice lacking H2‐K <jats:sup>b</jats:sup> D <jats:sup>b</jats:sup> (Tg/KO) were treated with ABC with or without IFN‐α or IFN‐γ blockade. Immune cell phenotype and functions were assessed via flow cytometry, and splenic transcriptomic profiles were analyzed to evaluate gene expression changes associated with treatment. Results ABC treatment of Tg/KO mice, which only express HLA‐B*57:01 as an MHC‐I allele, led to the expansion of drug‐specific CD8 <jats:sup>+</jats:sup> T‐cells, enhanced antigen presenting cell (APC) activity, and reduction in Tregs. These changes were accompanied by increased IFN‐α levels and plasmacytoid dendritic cell (pDC) maturation. Depletion of pDCs or blocking of IFN‐αR, in contrast to IFN‐γ blockade, restored Treg populations and diminished CD8 <jats:sup>+</jats:sup> T‐cell responses. These findings demonstrate that IFN‐α, primarily produced by pDCs, disrupts Treg expansion, whereas IFN‐γ predominantly enhances APC maturation and activation. Transcriptomic analysis revealed key genes regulated exclusively by ABC treatment in the presence of both IFN‐α and IFN‐γ signaling and demonstrated that IFN‐α signaling predominantly modulates innate and adaptive immune genes while supporting the downregulation of Treg‐related genes. Conclusions In vivo upregulation of HLA expression modulates the balance between drug‐specific and regulatory T cells, thereby promoting optimal pDC expansion and enhancing IFN‐α production, which counteracts Treg‐mediated ABC tolerance. IFN‐γ secretion by drug‐specific CD8 <jats:sup>+</jats:sup> T‐cells promoted APC and effector T‐cell function that led to the development of ABC‐associated hypersensitivity reactions in immunocompetent HLA Tg mice.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"179 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gunter Sturm, Maria Beatrice Bilò, Carmen Vidal, Joanna N.G. Oude Elberink, Jochen Schmitt, Andreas Kallsoy Slættanes, Thilo Jakob
Background Systemic sting reactions (SSRs) from bee and wasp stings can cause severe symptoms, including anaphylaxis and potentially lead to fatal outcomes. These reactions can significantly affect individuals' daily lives due to the fear and anxiety associated with the risk of stings. Venom immunotherapy (VIT) has been shown to be an effective preventive treatment for SSRs, offering a viable alternative to emergency treatments like adrenaline auto‐injectors (AAIs). Methods We created a decision tree framework with a Danish payer perspective designed to evaluate the cost‐effectiveness of VIT with Alutard ® SQ in individuals with bee and/or wasp venom allergies. Input in the model was identified from a structured literature review and expert consensus. The incremental cost‐effectiveness ratio (ICER) of Hymenoptera venom depot immunotherapy (HVDI) compared to AAIs over a 10‐year time horizon was estimated. The impact of uncertainty associated with key assumptions was investigated using univariate deterministic sensitivity analyses (DSA). Results In the base case, the incremental cost of HVDI was €7428, while the incremental quality‐adjusted life years (QALYs) gained were 0.48. Consequently, the ICER (cost per QALY) of HVDI compared to AAIs after 10 years was estimated at €15,550. Conclusion VIT is a cost‐effective treatment for the prevention of severe reactions to wasp and/or bee stings when compared to AAIs.
{"title":"Cost‐Effectiveness of Venom Immunotherapy in Preventing Severe Bee and Wasp Sting Reactions","authors":"Gunter Sturm, Maria Beatrice Bilò, Carmen Vidal, Joanna N.G. Oude Elberink, Jochen Schmitt, Andreas Kallsoy Slættanes, Thilo Jakob","doi":"10.1111/all.70176","DOIUrl":"https://doi.org/10.1111/all.70176","url":null,"abstract":"Background Systemic sting reactions (SSRs) from bee and wasp stings can cause severe symptoms, including anaphylaxis and potentially lead to fatal outcomes. These reactions can significantly affect individuals' daily lives due to the fear and anxiety associated with the risk of stings. Venom immunotherapy (VIT) has been shown to be an effective preventive treatment for SSRs, offering a viable alternative to emergency treatments like adrenaline auto‐injectors (AAIs). Methods We created a decision tree framework with a Danish payer perspective designed to evaluate the cost‐effectiveness of VIT with Alutard <jats:sup>®</jats:sup> SQ in individuals with bee and/or wasp venom allergies. Input in the model was identified from a structured literature review and expert consensus. The incremental cost‐effectiveness ratio (ICER) of Hymenoptera venom depot immunotherapy (HVDI) compared to AAIs over a 10‐year time horizon was estimated. The impact of uncertainty associated with key assumptions was investigated using univariate deterministic sensitivity analyses (DSA). Results In the base case, the incremental cost of HVDI was €7428, while the incremental quality‐adjusted life years (QALYs) gained were 0.48. Consequently, the ICER (cost per QALY) of HVDI compared to AAIs after 10 years was estimated at €15,550. Conclusion VIT is a cost‐effective treatment for the prevention of severe reactions to wasp and/or bee stings when compared to AAIs.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"39 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joanne Ellis, Léa Fortunato, Hannah Wajdner, Ester Del Duca, Joanna Barnard, Joanna C. Betts, Swaroop Bose, John Browning, Núria Buil‐Bruna, Scott Van Buren, Eden David, Scott Dinehart, Puneet Dhawan, Yeriel Estrada, Parima Ghafoori, Kiranmai Gumireddy, Zhenghong Li, Wei Jing Loo, Fiona Lovegrove, Jenny Lowe, Lawrence Charles Parish, Will Powley, Naveen Prasad, Joel Correa Da Rosa, Marieta Ruseva, Neda Shokrian, Farhat Syed, Chun‐Hang Tang, Gabriel K. Wong, John B. Kelly, Nicolas Wisniacki, Iain Uings, Emma Guttman‐Yassky
Background Interleukin‐18 (IL‐18) is a pleiotropic cytokine implicated in atopic dermatitis (AD), affecting both type (T)1 and T2 immune pathways. An anti–IL‐18 monoclonal antibody, aletekitug, was evaluated for its clinical and molecular effects in patients with moderate to severe AD. Methods This randomised, double‐blind, parallel‐group, placebo‐controlled, 24‐week study assessed adults with moderate‐to‐severe AD who were biologic‐naïve or dupilumab‐inadequate responders/intolerant. Participants received a single intravenous (IV) infusion of aletekitug 2 mg/kg or placebo. The primary endpoint was percentage change from baseline (PCFB) in Eczema Area and Severity Index (EASI) score at Week 12. Other endpoints included safety, patient‐reported outcomes (PROs) and transcriptomics. Results Thirty‐four participants (aletekitug, n = 23; placebo, n = 11) were randomised. A greater reduction in the PCFB in EASI score at Week 12 was demonstrated for patients who received aletekitug versus placebo (posterior median PCFB [95% credible intervals]: aletekitug, −68.3% [−79.68, −56.68]; placebo, −32.9% [−45.74, −21.10]), with effects still apparent at Week 24. Aletekitug improved PRO measures of itch, sleep disturbance, fatigue and quality of life versus placebo up to Week 24. Transcriptome analysis suggested aletekitug modulated lesional skin towards a non‐lesional profile and exerted broad immunomodulatory effects, impacting several AD‐associated signalling pathways, not limited to T2 immunity. Aletekitug was well tolerated, with no serious adverse events reported. Conclusion A single 2 mg/kg IV dose of aletekitug was associated with improved outcomes at Week 12, which were sustained to Week 24, and modulated immune mechanisms beyond T2 inflammation. These results support IL‐18 as a potential therapeutic target in moderate‐to‐severe AD.
{"title":"Clinical and Molecular Effect of the Anti– IL ‐18 Antibody Aletekitug in Adults With Atopic Dermatitis","authors":"Joanne Ellis, Léa Fortunato, Hannah Wajdner, Ester Del Duca, Joanna Barnard, Joanna C. Betts, Swaroop Bose, John Browning, Núria Buil‐Bruna, Scott Van Buren, Eden David, Scott Dinehart, Puneet Dhawan, Yeriel Estrada, Parima Ghafoori, Kiranmai Gumireddy, Zhenghong Li, Wei Jing Loo, Fiona Lovegrove, Jenny Lowe, Lawrence Charles Parish, Will Powley, Naveen Prasad, Joel Correa Da Rosa, Marieta Ruseva, Neda Shokrian, Farhat Syed, Chun‐Hang Tang, Gabriel K. Wong, John B. Kelly, Nicolas Wisniacki, Iain Uings, Emma Guttman‐Yassky","doi":"10.1111/all.70172","DOIUrl":"https://doi.org/10.1111/all.70172","url":null,"abstract":"Background Interleukin‐18 (IL‐18) is a pleiotropic cytokine implicated in atopic dermatitis (AD), affecting both type (T)1 and T2 immune pathways. An anti–IL‐18 monoclonal antibody, aletekitug, was evaluated for its clinical and molecular effects in patients with moderate to severe AD. Methods This randomised, double‐blind, parallel‐group, placebo‐controlled, 24‐week study assessed adults with moderate‐to‐severe AD who were biologic‐naïve or dupilumab‐inadequate responders/intolerant. Participants received a single intravenous (IV) infusion of aletekitug 2 mg/kg or placebo. The primary endpoint was percentage change from baseline (PCFB) in Eczema Area and Severity Index (EASI) score at Week 12. Other endpoints included safety, patient‐reported outcomes (PROs) and transcriptomics. Results Thirty‐four participants (aletekitug, <jats:italic>n</jats:italic> = 23; placebo, <jats:italic>n</jats:italic> = 11) were randomised. A greater reduction in the PCFB in EASI score at Week 12 was demonstrated for patients who received aletekitug versus placebo (posterior median PCFB [95% credible intervals]: aletekitug, −68.3% [−79.68, −56.68]; placebo, −32.9% [−45.74, −21.10]), with effects still apparent at Week 24. Aletekitug improved PRO measures of itch, sleep disturbance, fatigue and quality of life versus placebo up to Week 24. Transcriptome analysis suggested aletekitug modulated lesional skin towards a non‐lesional profile and exerted broad immunomodulatory effects, impacting several AD‐associated signalling pathways, not limited to T2 immunity. Aletekitug was well tolerated, with no serious adverse events reported. Conclusion A single 2 mg/kg IV dose of aletekitug was associated with improved outcomes at Week 12, which were sustained to Week 24, and modulated immune mechanisms beyond T2 inflammation. These results support IL‐18 as a potential therapeutic target in moderate‐to‐severe AD.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"22 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Helena Port, Misbah Noshela Ghazanfar, Ditte Georgina Zhang, Bea Borg, Alexander Egeberg, Jacob Pontoppidan Thyssen, Signe Holm Nielsen, Simon Francis Thomsen
{"title":"Crosslinked Fibrin Fragment (X‐ FIB ) as a Biomarker for Endotype Differentiation and Response to Omalizumab Treatment in Chronic Spontaneous Urticaria","authors":"Helena Port, Misbah Noshela Ghazanfar, Ditte Georgina Zhang, Bea Borg, Alexander Egeberg, Jacob Pontoppidan Thyssen, Signe Holm Nielsen, Simon Francis Thomsen","doi":"10.1111/all.70196","DOIUrl":"https://doi.org/10.1111/all.70196","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"112 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Duong Duc Pham, Hyouk‐Soo Kwon, Woo‐Jung Song, You Sook Cho, Sei Won Lee, Ga‐Young Ban, Taehoon Lee, So‐Young Park, Young‐Hee Nam, Byung‐Jae Lee, Jin An, Chan Sun Park, Hyo‐In Rhyou, Joo‐Hee Kim, Hye‐Kyung Park, Sang‐Ha Kim, Min‐Suk Yang, Min‐Hye Kim, Kyung‐Min Ahn, Ji‐Su Shim, Jeong‐Hee Choi, Sujeong Kim, Jae‐Woo Jung, Han Ki Park, Byung Keun Kim, Ji‐Hyang Lee, Young‐Chan Kim, Sang Min Lee, Sung‐Yoon Kang, Jae‐Woo Kwon, Gyu Young Hur, Ji‐Yong Moon, Kyoung‐Hee Sohn, Mi‐Ae Kim, Sae‐Hoon Kim, Sunyoung Yoon, An‐Soo Jang, Sang Hoon Kim, So Young Park, Hyun Jung Jin, So Ri Kim, Jae‐Hyun Lee, Pankaj K. Bhavsar, Ian M. Adcock, Dixey Piers, Nazanin Zounemat‐Kermani, Yang Freda, Pujan H. Patel, Kian Fan Chung, Tae‐Bum Kim
{"title":"Type 2 Biomarkers as Mediators of Clinical Remission With Biologics in Severe Asthma","authors":"Duong Duc Pham, Hyouk‐Soo Kwon, Woo‐Jung Song, You Sook Cho, Sei Won Lee, Ga‐Young Ban, Taehoon Lee, So‐Young Park, Young‐Hee Nam, Byung‐Jae Lee, Jin An, Chan Sun Park, Hyo‐In Rhyou, Joo‐Hee Kim, Hye‐Kyung Park, Sang‐Ha Kim, Min‐Suk Yang, Min‐Hye Kim, Kyung‐Min Ahn, Ji‐Su Shim, Jeong‐Hee Choi, Sujeong Kim, Jae‐Woo Jung, Han Ki Park, Byung Keun Kim, Ji‐Hyang Lee, Young‐Chan Kim, Sang Min Lee, Sung‐Yoon Kang, Jae‐Woo Kwon, Gyu Young Hur, Ji‐Yong Moon, Kyoung‐Hee Sohn, Mi‐Ae Kim, Sae‐Hoon Kim, Sunyoung Yoon, An‐Soo Jang, Sang Hoon Kim, So Young Park, Hyun Jung Jin, So Ri Kim, Jae‐Hyun Lee, Pankaj K. Bhavsar, Ian M. Adcock, Dixey Piers, Nazanin Zounemat‐Kermani, Yang Freda, Pujan H. Patel, Kian Fan Chung, Tae‐Bum Kim","doi":"10.1111/all.70186","DOIUrl":"https://doi.org/10.1111/all.70186","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"11 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Holly Boyd, Irene Bartha, Ru‐Xin Foong, Marta Krawiec, Andreina Marques‐Mejias, Hannah F. Marshall, Suzana Radulovic, Faye Harrison, Grammatiki Antoneria, Zainab Jama, Matthew Kwok, Ewa Pietraszewicz, Malak Eghleilib, Cristian Ricci, Tom Marrs, Gideon Lack, George Du Toit, Alexandra F. Santos
Background Cow's milk allergy is the most common food allergy worldwide and the top cause of food anaphylaxis fatalities. Identifying patients at higher risk of severe symptoms as well as patients with a lower threshold of reactivity would improve their management. We aimed to assess the utility of putative biomarkers to identify these high‐risk patients. Methods The severity of allergic reactions to baked milk ( BM ) and to fresh milk ( FM ) during oral food challenges ( OFC ) was assessed prospectively during the BAT2 study ( NCT03309488 ), according to the Practall guidelines. Demographic, clinical and immunological parameters were compared between severe/non‐severe and higher/lower threshold reactors to BM or FM . Receiver Operating Characteristic curve analyses were performed to measure the accuracy of biomarkers with discriminative ability. Results Seventy‐one children reacted to cow's milk: 22 (15%) to BM and 49 (43%) to FM . Seven (32%) and 12 (24%) reactors had severe symptoms during OFC to BM and FM , respectively. The median cumulative dose of milk protein tolerated was 0.44 g for BM and 0.143 g for FM . The basophil activation test ( BAT ) was the only biomarker that could distinguish severity and threshold groups. BAT optimal cut‐offs had 71% sensitivity and 100% specificity to identify severe reactors to BM and 96% sensitivity and 41% specificity to identify children reacting to 0.143 g or less of FM . Conclusions BAT was the only biomarker for severity and threshold of allergic reactions to BM and FM, respectively. Once applied to clinical practice, BAT can help risk‐stratify cow's milk allergic patients and improve their management.
{"title":"Basophil Activation Test as Biomarker of Severity and Threshold of Allergic Reactions to Cow's Milk During Oral Food Challenges","authors":"Holly Boyd, Irene Bartha, Ru‐Xin Foong, Marta Krawiec, Andreina Marques‐Mejias, Hannah F. Marshall, Suzana Radulovic, Faye Harrison, Grammatiki Antoneria, Zainab Jama, Matthew Kwok, Ewa Pietraszewicz, Malak Eghleilib, Cristian Ricci, Tom Marrs, Gideon Lack, George Du Toit, Alexandra F. Santos","doi":"10.1111/all.70175","DOIUrl":"https://doi.org/10.1111/all.70175","url":null,"abstract":"Background Cow's milk allergy is the most common food allergy worldwide and the top cause of food anaphylaxis fatalities. Identifying patients at higher risk of severe symptoms as well as patients with a lower threshold of reactivity would improve their management. We aimed to assess the utility of putative biomarkers to identify these high‐risk patients. Methods The severity of allergic reactions to baked milk ( <jats:styled-content style=\"fixed-case\">BM</jats:styled-content> ) and to fresh milk ( <jats:styled-content style=\"fixed-case\">FM</jats:styled-content> ) during oral food challenges ( <jats:styled-content style=\"fixed-case\">OFC</jats:styled-content> ) was assessed prospectively during the <jats:styled-content style=\"fixed-case\">BAT2</jats:styled-content> study ( <jats:styled-content style=\"fixed-case\">NCT03309488</jats:styled-content> ), according to the Practall guidelines. Demographic, clinical and immunological parameters were compared between severe/non‐severe and higher/lower threshold reactors to <jats:styled-content style=\"fixed-case\">BM</jats:styled-content> or <jats:styled-content style=\"fixed-case\">FM</jats:styled-content> . Receiver Operating Characteristic curve analyses were performed to measure the accuracy of biomarkers with discriminative ability. Results Seventy‐one children reacted to cow's milk: 22 (15%) to <jats:styled-content style=\"fixed-case\">BM</jats:styled-content> and 49 (43%) to <jats:styled-content style=\"fixed-case\">FM</jats:styled-content> . Seven (32%) and 12 (24%) reactors had severe symptoms during <jats:styled-content style=\"fixed-case\">OFC</jats:styled-content> to <jats:styled-content style=\"fixed-case\">BM</jats:styled-content> and <jats:styled-content style=\"fixed-case\">FM</jats:styled-content> , respectively. The median cumulative dose of milk protein tolerated was 0.44 g for <jats:styled-content style=\"fixed-case\">BM</jats:styled-content> and 0.143 g for <jats:styled-content style=\"fixed-case\">FM</jats:styled-content> . The basophil activation test ( <jats:styled-content style=\"fixed-case\">BAT</jats:styled-content> ) was the only biomarker that could distinguish severity and threshold groups. <jats:styled-content style=\"fixed-case\">BAT</jats:styled-content> optimal cut‐offs had 71% sensitivity and 100% specificity to identify severe reactors to <jats:styled-content style=\"fixed-case\">BM</jats:styled-content> and 96% sensitivity and 41% specificity to identify children reacting to 0.143 g or less of <jats:styled-content style=\"fixed-case\">FM</jats:styled-content> . Conclusions BAT was the only biomarker for severity and threshold of allergic reactions to BM and FM, respectively. Once applied to clinical practice, BAT can help risk‐stratify cow's milk allergic patients and improve their management.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"178 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carlo Maria Rossi, Ingrid Terreehorst, Evaggelia Apostolidou, Martina Votto, Arzu Bakirtas, Antonella Cianferroni, George N. Konstantinou, Katerina Pantavou, Dario Antolin‐Amerigo, Enrico Heffler, Alberto Alvarez‐Perea, Montserrat Fernandez‐Rivas, Georgios K. Nikolopoulos, Oliver Pfaar, Constantinos Pitsios
The European Academy of Allergy and Clinical Immunology (EAACI) established a Task Force to assess the existing data on the relationship between eosinophilic esophagitis (EoE) and allergen immunotherapy (AIT). This systematic review and meta‐analysis aimed to study the incidence of confirmed EoE, developing as a side effect of AIT to food or airborne allergens, following the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) 2020 guidelines. The literature search was performed in three databases (PubMed, Embase and Scopus). Databases were searched from inception to March 31st, 2023. A total of 17 studies met the criteria for inclusion in the review. Fifteen studies, comprising 3,302 patients, were on food desensitization, and the overall estimate of EoE incidence, combining the results of these individual studies, was 2.31% (95% CI 1.45, 3.36). Registered data reported de novo cases of eosinophilic esophagitis, and its diagnosis was usually made during the maintenance phase of food desensitization. With the adopted searching strategy, only two studies on sublingual immunotherapy with aeroallergens meeting the inclusion criteria were retrieved, comprising 1,436 patients and not reporting cases of EoE. The meta‐analysis showed that the development of EoE is a common adverse effect of oral immunotherapy with food allergens, whereas it is uncommon during sublingual immunotherapy with aeroallergens. Trial Registration: PROSPERO: CRD42023425917
欧洲过敏和临床免疫学学会（EAACI）成立了一个工作组来评估嗜酸性粒细胞性食管炎（EoE）和过敏原免疫治疗（AIT）之间关系的现有数据。本系统评价和荟萃分析旨在根据系统评价和荟萃分析（PRISMA） 2020指南的首选报告项目，研究确诊的EoE的发生率，这是AIT对食物或空气中过敏原的副作用。文献检索在PubMed、Embase和Scopus三个数据库中进行。数据库从成立到2023年3月31日进行了搜索。共有17项研究符合纳入本综述的标准。15项研究，包括3302名患者，是关于食物脱敏的，综合这些单独研究的结果，EoE发生率的总体估计为2.31% （95% CI 1.45, 3.36）。已登记的资料报道了嗜酸性粒细胞性食管炎的新发病例，其诊断通常在食物脱敏的维持阶段进行。采用检索策略，仅检索到两篇符合纳入标准的含气敏原的舌下免疫治疗研究，共1436例患者，未报告EoE病例。荟萃分析显示，EoE的发生是食物过敏原口服免疫治疗的常见不良反应，而在含空气过敏原的舌下免疫治疗中并不常见。试验注册：PROSPERO: CRD42023425917
{"title":"A Systematic Review and Meta‐Analysis on the Induction of Confirmed Eosinophilic Esophagitis as a Side Effect of Allergen Immunotherapy: An EAACI Task Force Report","authors":"Carlo Maria Rossi, Ingrid Terreehorst, Evaggelia Apostolidou, Martina Votto, Arzu Bakirtas, Antonella Cianferroni, George N. Konstantinou, Katerina Pantavou, Dario Antolin‐Amerigo, Enrico Heffler, Alberto Alvarez‐Perea, Montserrat Fernandez‐Rivas, Georgios K. Nikolopoulos, Oliver Pfaar, Constantinos Pitsios","doi":"10.1111/all.70183","DOIUrl":"https://doi.org/10.1111/all.70183","url":null,"abstract":"The European Academy of Allergy and Clinical Immunology (EAACI) established a Task Force to assess the existing data on the relationship between eosinophilic esophagitis (EoE) and allergen immunotherapy (AIT). This systematic review and meta‐analysis aimed to study the incidence of confirmed EoE, developing as a side effect of AIT to food or airborne allergens, following the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) 2020 guidelines. The literature search was performed in three databases (PubMed, Embase and Scopus). Databases were searched from inception to March 31st, 2023. A total of 17 studies met the criteria for inclusion in the review. Fifteen studies, comprising 3,302 patients, were on food desensitization, and the overall estimate of EoE incidence, combining the results of these individual studies, was 2.31% (95% CI 1.45, 3.36). Registered data reported <jats:italic>de novo</jats:italic> cases of eosinophilic esophagitis, and its diagnosis was usually made during the maintenance phase of food desensitization. With the adopted searching strategy, only two studies on sublingual immunotherapy with aeroallergens meeting the inclusion criteria were retrieved, comprising 1,436 patients and not reporting cases of EoE. The meta‐analysis showed that the development of EoE is a common adverse effect of oral immunotherapy with food allergens, whereas it is uncommon during sublingual immunotherapy with aeroallergens. Trial Registration: PROSPERO: CRD42023425917","PeriodicalId":122,"journal":{"name":"Allergy","volume":"15 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emilia Vassilopoulou, Sophia Tsabouri, Stefania Arasi, Anna Comotti, Gregorio Paolo Milani, Klaudia Ryczaj, Carlo Agostoni, Ioannis Pagkalos, Berber Vlieg‐Boerstra, Chrystopherson Gengyny Caballero‐Lopez, Gavriela Feketea, Anna Nowak‐Wegrzyn, Susanne Halken, Burcin Beken, Montserrat Alvaro‐Lozano, Ines Padua, Mattia Giovannini, George Du Toit, Alberto Alvarez‐Perea, Roberto Berni Canani, Diego Peroni, Marina Pérez‐Gordo, Mohamed H. Shamji, Ludger Klimek, Ioana Agache, Elena Camelia Berghea, Franziska Roth‐Walter, Cevdet Ozdemir, Peter Smith, Liam O’ Mahony, Rosan W. Meyer, Carina Venter
Complementary feeding (CF) influences infants' long‐term dietary preferences, growth, and food allergy (FA) risk. However, guidance given to families and the implementation of FA prevention guidelines by healthcare professionals (HCPs) remain unclear. This study explored HCPs' perspectives and practices regarding CF strategies in the context of FA prevention across different regions and professional backgrounds. An online survey conducted by an EAACI task force between December 2023 and May 2024 assessed CF timing, allergenic food introduction, nutrient supplementation, and FA preventive measures. 550 HCPs (pediatricians, allergists, dietitians), 68% from Europe, participated. HCPs recommended CF initiation at a median of six months for breastfed infants and five months for formula‐fed and FA high‐risk infants. Atopic dermatitis (94%) and family history of allergies (87%) were the most recognized FA risk factors. Vitamin D (49%), probiotics (28%), and omega‐3 fatty acids (18%) were commonly recommended supplements. Regional, professional, and educational influences differences emerged, with Northern European HCPs favoring earlier CF and allergen introduction, often without structured guidance. Southern European HCPs preferred a structured sequence and later CF initiation. A flexible, evidence‐based framework is needed to guide FA prevention while accommodating cultural and geographical differences.
{"title":"Healthcare Professional Survey on Complementary Feeding and Allergy Prevention in High‐ Versus Low‐Risk Infants: An EAACI Task Force Report","authors":"Emilia Vassilopoulou, Sophia Tsabouri, Stefania Arasi, Anna Comotti, Gregorio Paolo Milani, Klaudia Ryczaj, Carlo Agostoni, Ioannis Pagkalos, Berber Vlieg‐Boerstra, Chrystopherson Gengyny Caballero‐Lopez, Gavriela Feketea, Anna Nowak‐Wegrzyn, Susanne Halken, Burcin Beken, Montserrat Alvaro‐Lozano, Ines Padua, Mattia Giovannini, George Du Toit, Alberto Alvarez‐Perea, Roberto Berni Canani, Diego Peroni, Marina Pérez‐Gordo, Mohamed H. Shamji, Ludger Klimek, Ioana Agache, Elena Camelia Berghea, Franziska Roth‐Walter, Cevdet Ozdemir, Peter Smith, Liam O’ Mahony, Rosan W. Meyer, Carina Venter","doi":"10.1111/all.70188","DOIUrl":"https://doi.org/10.1111/all.70188","url":null,"abstract":"Complementary feeding (CF) influences infants' long‐term dietary preferences, growth, and food allergy (FA) risk. However, guidance given to families and the implementation of FA prevention guidelines by healthcare professionals (HCPs) remain unclear. This study explored HCPs' perspectives and practices regarding CF strategies in the context of FA prevention across different regions and professional backgrounds. An online survey conducted by an EAACI task force between December 2023 and May 2024 assessed CF timing, allergenic food introduction, nutrient supplementation, and FA preventive measures. 550 HCPs (pediatricians, allergists, dietitians), 68% from Europe, participated. HCPs recommended CF initiation at a median of six months for breastfed infants and five months for formula‐fed and FA high‐risk infants. Atopic dermatitis (94%) and family history of allergies (87%) were the most recognized FA risk factors. Vitamin D (49%), probiotics (28%), and omega‐3 fatty acids (18%) were commonly recommended supplements. Regional, professional, and educational influences differences emerged, with Northern European HCPs favoring earlier CF and allergen introduction, often without structured guidance. Southern European HCPs preferred a structured sequence and later CF initiation. A flexible, evidence‐based framework is needed to guide FA prevention while accommodating cultural and geographical differences.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"29 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145730993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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