Celine Galleani, María José Peñalver, Ruth Barranco, Ismael García-Moguel, Jesús F Crespo, Beatriz Cabanillas
{"title":"Cutaneous reactions during Helicobacter pylori eradication therapy referred to an Allergy Department.","authors":"Celine Galleani, María José Peñalver, Ruth Barranco, Ismael García-Moguel, Jesús F Crespo, Beatriz Cabanillas","doi":"10.1111/all.16344","DOIUrl":"https://doi.org/10.1111/all.16344","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374729","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}
Inmaculada Doña, María Salas, Esther Moreno, Marta Ferrer, Cristobalina Mayorga, María José Torres
{"title":"An algorithm for the diagnosis of betalactam allergy, 2024 update.","authors":"Inmaculada Doña, María Salas, Esther Moreno, Marta Ferrer, Cristobalina Mayorga, María José Torres","doi":"10.1111/all.16348","DOIUrl":"https://doi.org/10.1111/all.16348","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374728","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}
Inmaculada Doña, Rocío Sáenz de Santa María, Esther María Moreno, Joan Bartra, María José Torres
{"title":"An algorithm for the diagnosis and treatment of nonsteroidal antiinflammatory drugs hypersensitivity, 2024 update.","authors":"Inmaculada Doña, Rocío Sáenz de Santa María, Esther María Moreno, Joan Bartra, María José Torres","doi":"10.1111/all.16349","DOIUrl":"https://doi.org/10.1111/all.16349","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370333","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}
{"title":"Ushering in a new era in food allergy management with EAACI guidelines.","authors":"Scott H Sicherer","doi":"10.1111/all.16350","DOIUrl":"https://doi.org/10.1111/all.16350","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374730","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}
Mehdi Benamar, Peggy S Lai, Ching-Ying Huang, Qian Chen, Fatma Betul Oktelik, Paola Contini, Muyun Wang, Daniel Okin, Elena Crestani, Jason Fong, Tsz Man Chan Fion, Merve Nida Gokbak, Hani Harb, Wanda Phipatanakul, Luca Marri, Chiara Vassallo, Andrea Guastalla, Minsik Kim, Hui-Yu Sui, Lorenzo Berra, Marcia B Goldberg, Claudia Angelini, Raffaele De Palma, Talal A Chatila
Background: Immune dysregulation and SARS-CoV-2 plasma viremia have been implicated in fatal COVID-19 disease. However, how these two factors interact to shape disease outcomes is unclear.
Methods: We carried out viral and immunological phenotyping on a prospective cohort of 280 patients with COVID-19 presenting to acute care hospitals in Boston, Massachusetts and Genoa, Italy between June 1, 2020 and February 8, 2022. Disease severity, mortality, plasma viremia, and immune dysregulation were assessed. A mouse model of lethal H1N1 influenza infection was used to analyze the therapeutic potential of Notch4 and pyroptosis inhibition in disease outcome.
Results: Stratifying patients based on %Notch4+ Treg cells and/or the presence of plasma viremia identified four subgroups with different clinical trajectories and immune phenotypes. Patients with both high %Notch4+ Treg cells and viremia suffered the most disease severity and 90-day mortality compared to the other groups even after adjusting for baseline comorbidities. Increased Notch4 and plasma viremia impacted different arms of the immune response in SARS-CoV-2 infection. Increased Notch4 was associated with decreased Treg cell amphiregulin expression and suppressive function whereas plasma viremia was associated with increased monocyte cell pyroptosis. Combinatorial therapies using Notch4 blockade and pyroptosis inhibition induced stepwise protection against mortality in a mouse model of lethal H1N1 influenza infection.
Conclusions: The clinical trajectory and survival outcome in hospitalized patients with COVID-19 is predicated on two cardinal factors in disease pathogenesis: viremia and Notch4+ Treg cells. Intervention strategies aimed at resetting the immune dysregulation in COVID-19 by antagonizing Notch4 and pyroptosis may be effective in severe cases of viral lung infection.
{"title":"Notch4 regulatory T cells and SARS-CoV-2 viremia shape COVID19 survival outcome.","authors":"Mehdi Benamar, Peggy S Lai, Ching-Ying Huang, Qian Chen, Fatma Betul Oktelik, Paola Contini, Muyun Wang, Daniel Okin, Elena Crestani, Jason Fong, Tsz Man Chan Fion, Merve Nida Gokbak, Hani Harb, Wanda Phipatanakul, Luca Marri, Chiara Vassallo, Andrea Guastalla, Minsik Kim, Hui-Yu Sui, Lorenzo Berra, Marcia B Goldberg, Claudia Angelini, Raffaele De Palma, Talal A Chatila","doi":"10.1111/all.16333","DOIUrl":"https://doi.org/10.1111/all.16333","url":null,"abstract":"<p><strong>Background: </strong>Immune dysregulation and SARS-CoV-2 plasma viremia have been implicated in fatal COVID-19 disease. However, how these two factors interact to shape disease outcomes is unclear.</p><p><strong>Methods: </strong>We carried out viral and immunological phenotyping on a prospective cohort of 280 patients with COVID-19 presenting to acute care hospitals in Boston, Massachusetts and Genoa, Italy between June 1, 2020 and February 8, 2022. Disease severity, mortality, plasma viremia, and immune dysregulation were assessed. A mouse model of lethal H1N1 influenza infection was used to analyze the therapeutic potential of Notch4 and pyroptosis inhibition in disease outcome.</p><p><strong>Results: </strong>Stratifying patients based on %Notch4<sup>+</sup> Treg cells and/or the presence of plasma viremia identified four subgroups with different clinical trajectories and immune phenotypes. Patients with both high %Notch4<sup>+</sup> Treg cells and viremia suffered the most disease severity and 90-day mortality compared to the other groups even after adjusting for baseline comorbidities. Increased Notch4 and plasma viremia impacted different arms of the immune response in SARS-CoV-2 infection. Increased Notch4 was associated with decreased Treg cell amphiregulin expression and suppressive function whereas plasma viremia was associated with increased monocyte cell pyroptosis. Combinatorial therapies using Notch4 blockade and pyroptosis inhibition induced stepwise protection against mortality in a mouse model of lethal H1N1 influenza infection.</p><p><strong>Conclusions: </strong>The clinical trajectory and survival outcome in hospitalized patients with COVID-19 is predicated on two cardinal factors in disease pathogenesis: viremia and Notch4<sup>+</sup> Treg cells. Intervention strategies aimed at resetting the immune dysregulation in COVID-19 by antagonizing Notch4 and pyroptosis may be effective in severe cases of viral lung infection.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370334","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}
Pub Date : 2024-10-01Epub Date: 2024-06-22DOI: 10.1111/all.16178
Eve Denton, Mark Hew, Matthew J Peters, John W Upham, Lakmini Bulathsinhala, Trung N Tran, Neil Martin, Celine Bergeron, Mona Al-Ahmad, Alan Altraja, Désirée Larenas-Linnemann, Ruth Murray, Carlos Andrés Celis-Preciado, Riyad Al-Lehebi, Manon Belhassen, Mohit Bhutani, Sinthia Z Bosnic-Anticevich, Arnaud Bourdin, Guy G Brusselle, John Busby, Giorgio Walter Canonica, Enrico Heffler, Kenneth R Chapman, Jérémy Charriot, George C Christoff, Li Ping Chung, Borja G Cosio, Andréanne Côté, Richard W Costello, Breda Cushen, James Fingleton, João A Fonseca, Peter G Gibson, Liam G Heaney, Erick Wan-Chun Huang, Takashi Iwanaga, David J Jackson, Mariko Siyue Koh, Lauri Lehtimäki, Jorge Máspero, Bassam Mahboub, Andrew N Menzies-Gow, Patrick D Mitchell, Nikolaos G Papadopoulos, Andriana I Papaioannou, Luis Perez-de-Llano, Diahn-Warng Perng, Paul E Pfeffer, Todor A Popov, Celeste M Porsbjerg, Chin Kook Rhee, Nicolas Roche, Mohsen Sadatsafavi, Sundeep Salvi, Johannes Martin Schmid, Chau-Chyun Sheu, Concetta Sirena, Carlos A Torres-Duque, Laila Salameh, Pujan H Patel, Charlotte Suppli Ulrik, Eileen Wang, Michael E Wechsler, David B Price
Background: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma.
Methods: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day.
Results: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria.
Conclusions: Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria.
{"title":"Real-world biologics response and super-response in the International Severe Asthma Registry cohort.","authors":"Eve Denton, Mark Hew, Matthew J Peters, John W Upham, Lakmini Bulathsinhala, Trung N Tran, Neil Martin, Celine Bergeron, Mona Al-Ahmad, Alan Altraja, Désirée Larenas-Linnemann, Ruth Murray, Carlos Andrés Celis-Preciado, Riyad Al-Lehebi, Manon Belhassen, Mohit Bhutani, Sinthia Z Bosnic-Anticevich, Arnaud Bourdin, Guy G Brusselle, John Busby, Giorgio Walter Canonica, Enrico Heffler, Kenneth R Chapman, Jérémy Charriot, George C Christoff, Li Ping Chung, Borja G Cosio, Andréanne Côté, Richard W Costello, Breda Cushen, James Fingleton, João A Fonseca, Peter G Gibson, Liam G Heaney, Erick Wan-Chun Huang, Takashi Iwanaga, David J Jackson, Mariko Siyue Koh, Lauri Lehtimäki, Jorge Máspero, Bassam Mahboub, Andrew N Menzies-Gow, Patrick D Mitchell, Nikolaos G Papadopoulos, Andriana I Papaioannou, Luis Perez-de-Llano, Diahn-Warng Perng, Paul E Pfeffer, Todor A Popov, Celeste M Porsbjerg, Chin Kook Rhee, Nicolas Roche, Mohsen Sadatsafavi, Sundeep Salvi, Johannes Martin Schmid, Chau-Chyun Sheu, Concetta Sirena, Carlos A Torres-Duque, Laila Salameh, Pujan H Patel, Charlotte Suppli Ulrik, Eileen Wang, Michael E Wechsler, David B Price","doi":"10.1111/all.16178","DOIUrl":"10.1111/all.16178","url":null,"abstract":"<p><strong>Background: </strong>Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma.</p><p><strong>Methods: </strong>Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV<sub>1</sub>) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV<sub>1</sub> increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day.</p><p><strong>Results: </strong>5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV<sub>1</sub> increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria.</p><p><strong>Conclusions: </strong>Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141453914","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}
Pub Date : 2024-10-01Epub Date: 2024-06-16DOI: 10.1111/all.16195
Carlos Canelo-Aybar, Wendy Nieto-Gutierrez, L Yesenia Rodriguez-Tanta, Yahveth Cantero-Forti, Pablo Alonso-Coello, Marek Jutel, Cezmi A Akdis, Ioana Agache
{"title":"Reply to correspondence: Correspondence to \"The impact of indoor pollution on asthma-related outcomes: A systematic review for the EAACI guidelines on environmental science for allergic diseases and asthma\".","authors":"Carlos Canelo-Aybar, Wendy Nieto-Gutierrez, L Yesenia Rodriguez-Tanta, Yahveth Cantero-Forti, Pablo Alonso-Coello, Marek Jutel, Cezmi A Akdis, Ioana Agache","doi":"10.1111/all.16195","DOIUrl":"10.1111/all.16195","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141329814","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}
Pub Date : 2024-10-01Epub Date: 2024-08-04DOI: 10.1111/all.16259
Alexandra J McCraw, Lais C G F Palhares, Jenifer L Hendel, Richard A Gardner, Aida Santaolalla, Silvia Crescioli, James McDonnell, Mieke Van Hemelrijck, Alicia Chenoweth, Daniel I R Spencer, Gerd K Wagner, Sophia N Karagiannis
The impact of human IgE glycosylation on structure, function and disease mechanisms is not fully elucidated, and heterogeneity in different studies renders drawing conclusions challenging. Previous reviews discussed IgE glycosylation focusing on specific topics such as health versus disease, FcεR binding or impact on function. We present the first systematic review of human IgE glycosylation conducted utilizing the PRISMA guidelines. We sought to define the current consensus concerning the roles of glycosylation on structure, biology and disease. Despite diverse analytical methodologies, source, expression systems and the sparsity of data on IgE antibodies from non-allergic individuals, collectively evidence suggests differential glycosylation profiles, particularly in allergic diseases compared with healthy states, and indicates functional impact, and contributions to IgE-mediated hypersensitivities and atopic diseases. Beyond allergic diseases, dysregulated terminal glycan structures, including sialic acid, may regulate IgE metabolism. Glycan sites such as N394 may contribute to stabilizing IgE structure, with alterations in these glycans likely influencing both structure and IgE-FcεR interactions. This systematic review therefore highlights critical IgE glycosylation attributes in health and disease that may be exploitable for therapeutic intervention, and the need for novel analytics to explore pertinent research avenues.
{"title":"IgE glycosylation and impact on structure and function: A systematic review.","authors":"Alexandra J McCraw, Lais C G F Palhares, Jenifer L Hendel, Richard A Gardner, Aida Santaolalla, Silvia Crescioli, James McDonnell, Mieke Van Hemelrijck, Alicia Chenoweth, Daniel I R Spencer, Gerd K Wagner, Sophia N Karagiannis","doi":"10.1111/all.16259","DOIUrl":"10.1111/all.16259","url":null,"abstract":"<p><p>The impact of human IgE glycosylation on structure, function and disease mechanisms is not fully elucidated, and heterogeneity in different studies renders drawing conclusions challenging. Previous reviews discussed IgE glycosylation focusing on specific topics such as health versus disease, FcεR binding or impact on function. We present the first systematic review of human IgE glycosylation conducted utilizing the PRISMA guidelines. We sought to define the current consensus concerning the roles of glycosylation on structure, biology and disease. Despite diverse analytical methodologies, source, expression systems and the sparsity of data on IgE antibodies from non-allergic individuals, collectively evidence suggests differential glycosylation profiles, particularly in allergic diseases compared with healthy states, and indicates functional impact, and contributions to IgE-mediated hypersensitivities and atopic diseases. Beyond allergic diseases, dysregulated terminal glycan structures, including sialic acid, may regulate IgE metabolism. Glycan sites such as N394 may contribute to stabilizing IgE structure, with alterations in these glycans likely influencing both structure and IgE-FcεR interactions. This systematic review therefore highlights critical IgE glycosylation attributes in health and disease that may be exploitable for therapeutic intervention, and the need for novel analytics to explore pertinent research avenues.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887615","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}
Pub Date : 2024-10-01Epub Date: 2024-08-16DOI: 10.1111/all.16283
Rory Chan, Kirsten Stewart, Chris RuiWen Kuo, Brian Lipworth
{"title":"Indirect case-matched comparison of anti-IL4Rα versus anti-IL5Rα on airway hyperresponsiveness.","authors":"Rory Chan, Kirsten Stewart, Chris RuiWen Kuo, Brian Lipworth","doi":"10.1111/all.16283","DOIUrl":"10.1111/all.16283","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994809","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}
Kathleen M Buchheit, Dominick Shaw, Geoffrey Chupp, Lauri Lehtimaki, Enrico Heffler, Tricia Finney-Hayward, James Zangrilli, Justin Kwiatek, Salman Siddiqui, Florence Roufosse, Andrew Thamboo, Nicholas West, Anna Vichiendilokkul, Peter W Hellings, Anju Peters, Peter H Howarth
Interleukin (IL)-5 is the key cytokine in the maturation, activation, proliferation, migration and survival of eosinophils, which are key effector cells in many upper and lower airway diseases. Through its effects on eosinophils, IL-5 indirectly contributes to various pathophysiological processes including tissue damage, repair and remodelling. Understanding the importance of IL-5 in eosinophil-associated diseases led to the development of anti-IL-5 therapies, which provide clinical benefits across a range of conditions. However, recent evidence suggests that eosinophil-depletion alone may not account for all of the therapeutic effects of anti-IL-5 therapy and that IL-5 may also contribute to disease independently of its effects on eosinophils. Indeed, evidence from ex vivo studies and targeted therapy in vivo demonstrates that IL-5 and its inhibition affects a much broader range of cells beyond eosinophils, including epithelial cells, plasma cells, mast cells, basophils, neutrophils, type 2 innate lymphoid cells, T regulatory cells and fibroblasts. This review will provide an update on the evidence supporting the breadth of IL-5 biology relevant to disease pathogenesis beyond eosinophil-associated inflammation, where there is a need for additional insight, and the clinical implications of a more central role of IL-5 in type 2 inflammation.
{"title":"Interleukin-5 as a pleiotropic cytokine orchestrating airway type 2 inflammation: Effects on and beyond eosinophils.","authors":"Kathleen M Buchheit, Dominick Shaw, Geoffrey Chupp, Lauri Lehtimaki, Enrico Heffler, Tricia Finney-Hayward, James Zangrilli, Justin Kwiatek, Salman Siddiqui, Florence Roufosse, Andrew Thamboo, Nicholas West, Anna Vichiendilokkul, Peter W Hellings, Anju Peters, Peter H Howarth","doi":"10.1111/all.16303","DOIUrl":"https://doi.org/10.1111/all.16303","url":null,"abstract":"<p><p>Interleukin (IL)-5 is the key cytokine in the maturation, activation, proliferation, migration and survival of eosinophils, which are key effector cells in many upper and lower airway diseases. Through its effects on eosinophils, IL-5 indirectly contributes to various pathophysiological processes including tissue damage, repair and remodelling. Understanding the importance of IL-5 in eosinophil-associated diseases led to the development of anti-IL-5 therapies, which provide clinical benefits across a range of conditions. However, recent evidence suggests that eosinophil-depletion alone may not account for all of the therapeutic effects of anti-IL-5 therapy and that IL-5 may also contribute to disease independently of its effects on eosinophils. Indeed, evidence from ex vivo studies and targeted therapy in vivo demonstrates that IL-5 and its inhibition affects a much broader range of cells beyond eosinophils, including epithelial cells, plasma cells, mast cells, basophils, neutrophils, type 2 innate lymphoid cells, T regulatory cells and fibroblasts. This review will provide an update on the evidence supporting the breadth of IL-5 biology relevant to disease pathogenesis beyond eosinophil-associated inflammation, where there is a need for additional insight, and the clinical implications of a more central role of IL-5 in type 2 inflammation.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363562","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}