Pub Date : 2024-07-12DOI: 10.3389/falgy.2024.1440360
Elif Öztemiz Topcu, Gabriele Gadermaier
Antigen uptake and processing of exogenous proteins is critical for adaptive immunity, particularly for T helper cell activation. Proteins undergo distinct proteolytic processing in endolysosomal compartments of antigen-presenting cells. The resulting peptides are presented on MHC class II molecules and specifically recognized by T cells. The in vitro endolysosomal degradation assay mimics antigen processing by incubating a protein of interest with a protease cocktail derived from the endolysosomal compartments of antigen presenting cells. The kinetics of protein degradation is monitored by gel electrophoresis and allows calculation of a protein's half-life and thus endolysosomal stability. Processed peptides are analyzed by mass spectrometry and abundant peptide clusters are shown to harbor T cell epitopes. The endolysosomal degradation assay has been widely used to study allergens, which are IgE-binding proteins involved in type I hypersensitivity. In this review article, we provide the first comprehensive overview of the endolysosomal degradation of 29 isoallergens and variants originating from the PR-10, Ole e 1-like, pectate lyase, defensin polyproline-linked, non-specific lipid transfer, mite group 1, 2, and 5, and tropomyosin protein families. The assay method is described in detail and suggestions for improved standardization and reproducibility are provided. The current hypothesis implies that proteins with high endolysosomal stability can induce an efficient immune response, whereas highly unstable proteins are degraded early during antigen processing and therefore not efficient for MHC II peptide presentation. To validate this concept, systematic analyses of high and low allergenic representatives of protein families should be investigated. In addition to purified molecules, allergen extracts should be degraded to analyze potential matrix effects and gastrointestinal proteolysis of food allergens. In conclusion, individual protein susceptibility and peptides obtained from the endolysosomal degradation assay are powerful tools for understanding protein immunogenicity and T cell reactivity. Systematic studies and linkage with in vivo sensitization data will allow the establishment of (machine-learning) tools to aid prediction of immunogenicity and allergenicity. The orthogonal method could in the future be used for risk assessment of novel foods and in the generation of protein-based immunotherapeutics.
外源蛋白质的抗原摄取和加工对适应性免疫,尤其是对 T 辅助细胞的活化至关重要。蛋白质在抗原递呈细胞的内溶酶体区进行不同的蛋白水解处理。由此产生的多肽呈现在 MHC II 类分子上,并被 T 细胞特异性识别。体外内溶酶体降解试验通过将相关蛋白质与来自抗原呈递细胞内溶酶体区的鸡尾酒蛋白酶进行孵育,模拟抗原加工过程。通过凝胶电泳监测蛋白质降解的动力学,计算蛋白质的半衰期,从而计算内溶酶体稳定性。通过质谱分析处理后的肽,可以发现丰富的肽群蕴藏着 T 细胞表位。内溶酶体降解试验已被广泛用于研究过敏原,过敏原是参与 I 型超敏反应的 IgE 结合蛋白。在这篇综述文章中,我们首次全面概述了源自 PR-10、Ole e 1-like、果胶酸裂解酶、多脯氨酸连接防御素、非特异性脂质转移、螨类 1、2 和 5 以及肌球蛋白家族的 29 种异过敏原和变体的内溶酶体降解情况。详细介绍了检测方法,并就如何提高标准化和可重复性提出了建议。目前的假说暗示,具有高溶酶体内稳定性的蛋白质可诱导有效的免疫反应,而高度不稳定的蛋白质在抗原加工过程中会被提前降解,因此不能有效地进行 MHC II 多肽展示。为了验证这一概念,应该对蛋白质家族中高过敏性和低过敏性的代表进行系统分析。除纯化分子外,还应对过敏原提取物进行降解,以分析食物过敏原的潜在基质效应和胃肠道蛋白水解作用。总之,从溶酶体内降解试验中获得的单个蛋白质易感性和肽是了解蛋白质免疫原性和 T 细胞反应性的有力工具。系统性研究以及与体内致敏数据的联系将有助于建立(机器学习)工具,帮助预测免疫原性和致敏性。这种正交方法将来可用于新型食品的风险评估和基于蛋白质的免疫疗法的研发。
{"title":"To stay or not to stay intact as an allergen: the endolysosomal degradation assay used as tool to analyze protein immunogenicity and T cell epitopes","authors":"Elif Öztemiz Topcu, Gabriele Gadermaier","doi":"10.3389/falgy.2024.1440360","DOIUrl":"https://doi.org/10.3389/falgy.2024.1440360","url":null,"abstract":"Antigen uptake and processing of exogenous proteins is critical for adaptive immunity, particularly for T helper cell activation. Proteins undergo distinct proteolytic processing in endolysosomal compartments of antigen-presenting cells. The resulting peptides are presented on MHC class II molecules and specifically recognized by T cells. The in vitro endolysosomal degradation assay mimics antigen processing by incubating a protein of interest with a protease cocktail derived from the endolysosomal compartments of antigen presenting cells. The kinetics of protein degradation is monitored by gel electrophoresis and allows calculation of a protein's half-life and thus endolysosomal stability. Processed peptides are analyzed by mass spectrometry and abundant peptide clusters are shown to harbor T cell epitopes. The endolysosomal degradation assay has been widely used to study allergens, which are IgE-binding proteins involved in type I hypersensitivity. In this review article, we provide the first comprehensive overview of the endolysosomal degradation of 29 isoallergens and variants originating from the PR-10, Ole e 1-like, pectate lyase, defensin polyproline-linked, non-specific lipid transfer, mite group 1, 2, and 5, and tropomyosin protein families. The assay method is described in detail and suggestions for improved standardization and reproducibility are provided. The current hypothesis implies that proteins with high endolysosomal stability can induce an efficient immune response, whereas highly unstable proteins are degraded early during antigen processing and therefore not efficient for MHC II peptide presentation. To validate this concept, systematic analyses of high and low allergenic representatives of protein families should be investigated. In addition to purified molecules, allergen extracts should be degraded to analyze potential matrix effects and gastrointestinal proteolysis of food allergens. In conclusion, individual protein susceptibility and peptides obtained from the endolysosomal degradation assay are powerful tools for understanding protein immunogenicity and T cell reactivity. Systematic studies and linkage with in vivo sensitization data will allow the establishment of (machine-learning) tools to aid prediction of immunogenicity and allergenicity. The orthogonal method could in the future be used for risk assessment of novel foods and in the generation of protein-based immunotherapeutics.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141654462","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 : 2024-07-10DOI: 10.3389/falgy.2024.1440549
Ervin Ç. Mingomataj, Tayseer Ibrahim, Syed A. Rizvi
{"title":"Editorial: Biological therapy for allergic diseases: peculiarities, prospects, and challenges","authors":"Ervin Ç. Mingomataj, Tayseer Ibrahim, Syed A. Rizvi","doi":"10.3389/falgy.2024.1440549","DOIUrl":"https://doi.org/10.3389/falgy.2024.1440549","url":null,"abstract":"","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141659279","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 : 2024-07-10DOI: 10.3389/falgy.2024.1415124
A. C. Retzinger, G. Retzinger
Allergy and its manifestations were first appreciated in the 1870 s. Today, the mechanism by which specific substances elicit allergic reactions remains poorly understood. This is problematic from a healthcare perspective because the prevalence of allergic disease and its societal costs are substantial. Regarding mechanistic understanding of allergy, a new proposal, The Acari Hypothesis, has been forwarded. The Hypothesis, borne from consideration of alpha-gal syndrome, postulates that acarians, i.e., mites and ticks, are operative agents of allergy. By way of their pathogenic payloads and salivary pattern recognition receptor(s), acarians potentiate in human hosts the generation of IgE against acarian dietary elements. Those elements account for most, if not all, known human allergens. Inasmuch as acarian—human interactions occur on human epithelial surfaces, it is to be expected factors that influence the presence and/or operation of acarians on those surfaces influence the expression of allergic diseases. In this report, it is proposed that two adaptations of catarrhine primates, i.e., Old World monkeys, apes and humans, evolved to deter acarian species: firstly, the expansion of eccrine glands across the entirety of body surface area, and, secondly, the secretion of sweat by those glands. Contemporary hygienic practices that reduce and/or disrupt the operation of eccrine glands are likely responsible for the increase in allergic disease seen today.
{"title":"The Acari Hypothesis, IV: revisiting the role of hygiene in allergy","authors":"A. C. Retzinger, G. Retzinger","doi":"10.3389/falgy.2024.1415124","DOIUrl":"https://doi.org/10.3389/falgy.2024.1415124","url":null,"abstract":"Allergy and its manifestations were first appreciated in the 1870 s. Today, the mechanism by which specific substances elicit allergic reactions remains poorly understood. This is problematic from a healthcare perspective because the prevalence of allergic disease and its societal costs are substantial. Regarding mechanistic understanding of allergy, a new proposal, The Acari Hypothesis, has been forwarded. The Hypothesis, borne from consideration of alpha-gal syndrome, postulates that acarians, i.e., mites and ticks, are operative agents of allergy. By way of their pathogenic payloads and salivary pattern recognition receptor(s), acarians potentiate in human hosts the generation of IgE against acarian dietary elements. Those elements account for most, if not all, known human allergens. Inasmuch as acarian—human interactions occur on human epithelial surfaces, it is to be expected factors that influence the presence and/or operation of acarians on those surfaces influence the expression of allergic diseases. In this report, it is proposed that two adaptations of catarrhine primates, i.e., Old World monkeys, apes and humans, evolved to deter acarian species: firstly, the expansion of eccrine glands across the entirety of body surface area, and, secondly, the secretion of sweat by those glands. Contemporary hygienic practices that reduce and/or disrupt the operation of eccrine glands are likely responsible for the increase in allergic disease seen today.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141661701","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 : 2024-07-09DOI: 10.3389/falgy.2024.1426816
Alain Jacquet, Wai Tuck Soh
From their expression in their respective allergenic source to their processing by antigen presenting cells, allergens continuously encounter proteases. The ability of allergens to resist to proteolysis by digestive enzymes or host-cell/microbial proteases is considered as an important property that influences their allergenic potential. However, the relationship between proteolytic stability and allergenicity is much more complex and depends on various factors, such as the protein structure dynamics, the exposure level, the route of sensitization, and their respective protease susceptibility. In this review, we summarize and discuss the current knowledge on several aspects of allergen proteolytic stability in different environments including the allergenic sources, routes of sensitization (skin, respiratory tract, gastrointestinal tract) and endolysosomal compartment of antigen-presenting cells. Proteolytic stability alone cannot represent a definitive criterion to allergenicity. The proteolytic susceptibility of allergens in processed extracts can affect allergy diagnosis and immunotherapy. Furthermore, the fine tuning of allergen stability during antigen processing can be exploited for the development of novel immunotherapeutic strategies.
{"title":"Spatiotemporal proteolytic susceptibility of allergens: positive or negative effects on the allergic sensitization?","authors":"Alain Jacquet, Wai Tuck Soh","doi":"10.3389/falgy.2024.1426816","DOIUrl":"https://doi.org/10.3389/falgy.2024.1426816","url":null,"abstract":"From their expression in their respective allergenic source to their processing by antigen presenting cells, allergens continuously encounter proteases. The ability of allergens to resist to proteolysis by digestive enzymes or host-cell/microbial proteases is considered as an important property that influences their allergenic potential. However, the relationship between proteolytic stability and allergenicity is much more complex and depends on various factors, such as the protein structure dynamics, the exposure level, the route of sensitization, and their respective protease susceptibility. In this review, we summarize and discuss the current knowledge on several aspects of allergen proteolytic stability in different environments including the allergenic sources, routes of sensitization (skin, respiratory tract, gastrointestinal tract) and endolysosomal compartment of antigen-presenting cells. Proteolytic stability alone cannot represent a definitive criterion to allergenicity. The proteolytic susceptibility of allergens in processed extracts can affect allergy diagnosis and immunotherapy. Furthermore, the fine tuning of allergen stability during antigen processing can be exploited for the development of novel immunotherapeutic strategies.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141664625","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 : 2024-07-05DOI: 10.3389/falgy.2024.1383079
S. González-Díaz, Grecia Jaqueline Hernández-Salcido, C. D. de Lira‐Quezada, J. A. Cantú-Hernández, C. Macouzet-Sánchez, A. Macías-Weinmann, Natalhie Acuña-Ortega
Sick building syndrome (SBS) refers to non-specific complaints, including upper-respiratory irritative symptoms, headaches, fatigue, and rash, which are usually associated with a particular building by their temporal pattern of occurrence and clustering among inhabitants or colleagues. The aim of the study was to determine the association between the clinical manifestations of sick building syndrome with outdoor pollutants and airborne pollen.It was a descriptive and prospective observational study conducted from November 2021 to April 2022. It included subjects over 18 years old who completed an online survey on sick building syndrome (general symptoms, nasal, ocular, oropharyngeal, and skin symptoms) presented at home, housing information and personal history. The APS-330 from Pollen Sense ® was used to obtain data on pollen in the air and the local pollution monitoring system (SIMA) to obtain information regarding pollutants. For statistical analysis, SPSS version 16 was used.A total of 402 surveys were included; 91% of the subjects reported having at least 1 symptom. Females presented more general symptoms (fatigue and headache) than males. Subjects with a personal history of atopy showed a higher prevalence of practically all symptoms. Airborne pollen exposure was positively associated with mucosal symptoms in eyes and nose. Outdoor fungi spore exposure was positively associated with oculo-nasal and cutaneous symptoms in the scalp.This study found significant associations with female gender and a history of atopy, which suggests a higher risk for these subjects. Despite the limitations of the study, we can conclude that there is an association between the clinical manifestations of sick building syndrome with indoor and outdoor pollution.
{"title":"Sick building syndrome: do outdoor pollutants and pollen affect it?","authors":"S. González-Díaz, Grecia Jaqueline Hernández-Salcido, C. D. de Lira‐Quezada, J. A. Cantú-Hernández, C. Macouzet-Sánchez, A. Macías-Weinmann, Natalhie Acuña-Ortega","doi":"10.3389/falgy.2024.1383079","DOIUrl":"https://doi.org/10.3389/falgy.2024.1383079","url":null,"abstract":"Sick building syndrome (SBS) refers to non-specific complaints, including upper-respiratory irritative symptoms, headaches, fatigue, and rash, which are usually associated with a particular building by their temporal pattern of occurrence and clustering among inhabitants or colleagues. The aim of the study was to determine the association between the clinical manifestations of sick building syndrome with outdoor pollutants and airborne pollen.It was a descriptive and prospective observational study conducted from November 2021 to April 2022. It included subjects over 18 years old who completed an online survey on sick building syndrome (general symptoms, nasal, ocular, oropharyngeal, and skin symptoms) presented at home, housing information and personal history. The APS-330 from Pollen Sense ® was used to obtain data on pollen in the air and the local pollution monitoring system (SIMA) to obtain information regarding pollutants. For statistical analysis, SPSS version 16 was used.A total of 402 surveys were included; 91% of the subjects reported having at least 1 symptom. Females presented more general symptoms (fatigue and headache) than males. Subjects with a personal history of atopy showed a higher prevalence of practically all symptoms. Airborne pollen exposure was positively associated with mucosal symptoms in eyes and nose. Outdoor fungi spore exposure was positively associated with oculo-nasal and cutaneous symptoms in the scalp.This study found significant associations with female gender and a history of atopy, which suggests a higher risk for these subjects. Despite the limitations of the study, we can conclude that there is an association between the clinical manifestations of sick building syndrome with indoor and outdoor pollution.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141674495","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}
{"title":"Editorial: Exploring the role of adaptive immunity in chronic airway respiratory diseases.","authors":"Evangelia Fouka, Apostolos Bossios, Paschalis Steiropoulos, Konstantinos Samitas","doi":"10.3389/falgy.2024.1446656","DOIUrl":"10.3389/falgy.2024.1446656","url":null,"abstract":"","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11233784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141582020","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 : 2024-06-18eCollection Date: 2024-01-01DOI: 10.3389/falgy.2024.1301834
Michael A Golding, Manvir Bhamra, Zoe Harbottle, Moshe Ben-Shoshan, Jennifer D Gerdts, Leslie E Roos, Elissa M Abrams, Sara J Penner, Jo-Anne St-Vincent, Jennifer L P Protudjer
Introduction: Compared to households not managing food allergy, households managing food allergy are faced with greater direct and indirect costs. To address these cost burdens, we developed and piloted a milk allergy-friendly food supplement program for lower- and middle-income households managing a dairy allergy in a child age <6 years. Herein, we aimed to evaluate to the impact of this program on food costs, food security, and caregiver mental health using a longitudinal design.
Methods: Participants living in or near the city of Winnipeg, in Manitoba, Canada were recruited from January to February 2022 via social media, word-of-mouth, and a database maintained by the principal investigator. Consenting participants took part in a 6-month allergen-friendly food supplement program that provided them with biweekly deliveries of allergen-friendly foods free of charge. To evaluate the impact of the program on food costs, food security, and well-being, participants completed a series of questionnaires at baseline, mid-point, and at the end of the program. Changes in these variables were assessed via a series of Friedman tests.
Results: The final sample was comprised of 8 households. Relative to baseline, participants reported higher total direct food costs at midpoint (+5.6%) and endpoint (+13.5%), but these changes did not reach statistical significance. In contrast, total indirect food costs decreased over the course of the study relative to baseline (midpoint = -28.2%; endpoint = -18.5%), but the changes were not found to be statistically significant. Participants did, however, report a statistically significant decrease in costs related to lost time from work or school as a result of their child's food allergy at endpoint relative to baseline (-100%). Few changes in food security, caregiver well-being, or child food allergy quality of life were noted.
Discussion: The provision of allergen-friendly foods helped keep grocery costs below the pace of inflation. Participants also reported reduced costs associated with missed time from work or school as a result of their child's food allergy. Despite these encouraging findings, a relatively high proportion of the current sample reported experiencing food insecurity throughout the study period, suggesting that additional financial support for families is needed.
{"title":"An investigation of a novel milk allergy-friendly food supplement program.","authors":"Michael A Golding, Manvir Bhamra, Zoe Harbottle, Moshe Ben-Shoshan, Jennifer D Gerdts, Leslie E Roos, Elissa M Abrams, Sara J Penner, Jo-Anne St-Vincent, Jennifer L P Protudjer","doi":"10.3389/falgy.2024.1301834","DOIUrl":"10.3389/falgy.2024.1301834","url":null,"abstract":"<p><strong>Introduction: </strong>Compared to households not managing food allergy, households managing food allergy are faced with greater direct and indirect costs. To address these cost burdens, we developed and piloted a milk allergy-friendly food supplement program for lower- and middle-income households managing a dairy allergy in a child age <6 years. Herein, we aimed to evaluate to the impact of this program on food costs, food security, and caregiver mental health using a longitudinal design.</p><p><strong>Methods: </strong>Participants living in or near the city of Winnipeg, in Manitoba, Canada were recruited from January to February 2022 via social media, word-of-mouth, and a database maintained by the principal investigator. Consenting participants took part in a 6-month allergen-friendly food supplement program that provided them with biweekly deliveries of allergen-friendly foods free of charge. To evaluate the impact of the program on food costs, food security, and well-being, participants completed a series of questionnaires at baseline, mid-point, and at the end of the program. Changes in these variables were assessed via a series of Friedman tests.</p><p><strong>Results: </strong>The final sample was comprised of 8 households. Relative to baseline, participants reported higher total direct food costs at midpoint (+5.6%) and endpoint (+13.5%), but these changes did not reach statistical significance. In contrast, total indirect food costs decreased over the course of the study relative to baseline (midpoint = -28.2%; endpoint = -18.5%), but the changes were not found to be statistically significant. Participants did, however, report a statistically significant decrease in costs related to lost time from work or school as a result of their child's food allergy at endpoint relative to baseline (-100%). Few changes in food security, caregiver well-being, or child food allergy quality of life were noted.</p><p><strong>Discussion: </strong>The provision of allergen-friendly foods helped keep grocery costs below the pace of inflation. Participants also reported reduced costs associated with missed time from work or school as a result of their child's food allergy. Despite these encouraging findings, a relatively high proportion of the current sample reported experiencing food insecurity throughout the study period, suggesting that additional financial support for families is needed.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11217183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494460","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 : 2024-06-13DOI: 10.3389/falgy.2024.1348769
E. Robert, H. A. Al-Hashmi, A. Al-Mehaidib, K. Alsarraf, M. Al-Turaiki, W. Aldekhail, W. Al-Herz, A. Alkhabaz, Khalid O. Bawakid, A. Elghoudi, M. El Hodhod, Ali A. Hussain, N. Kamal, L. T. Goronfolah, B. Nasrallah, K. Sengupta, I. Broekaert, M. Domellöf, F. Indrio, A. Lapillonne, C. Pienar, C. Ribes-Koninckx, R. Shamir, H. Szajewska, N. Thapar, R. A. Thomassen, E. Verduci, C. West, Y. Vandenplas
The diagnosis and management of cow's milk allergy (CMA) is a topic of debate and controversy. Our aim was to compare the opinions of expert groups from the Middle East (n = 14) and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (n = 13).These Expert groups voted on statements that were developed by the ESPGHAN group and published in a recent position paper. The voting outcome was compared.Overall, there was consensus amongst both groups of experts. Experts agreed that symptoms of crying, irritability and colic, as single manifestation, are not suggestive of CMA. They agreed that amino-acid based formula (AAF) should be reserved for severe cases (e.g., malnutrition and anaphylaxis) and that there is insufficient evidence to recommend a step-down approach. There was no unanimous consensus on the statement that a cow's milk based extensively hydrolysed formula (eHF) should be the first choice as a diagnostic elimination diet in mild/moderate cases. Although the statements regarding the role for hydrolysed rice formula as a diagnostic and therapeutic elimination diet were accepted, 3/27 disagreed. The votes regarding soy formula highlight the differences in opinion in the role of soy protein in CMA dietary treatment. Generally, soy-based formula is seldom available in the Middle-East region. All ESPGHAN experts agreed that there is insufficient evidence that the addition of probiotics, prebiotics and synbiotics increase the efficacy of elimination diets regarding CMA symptoms (despite other benefits such as decrease of infections and antibiotic intake), whereas 3/14 of the Middle East group thought there was sufficient evidence.Differences in voting are related to geographical, cultural and other conditions, such as cost and availability. This emphasizes the need to develop region-specific guidelines considering social and cultural conditions, and to perform further research in this area.
{"title":"Symptoms and management of cow's milk allergy: perception and evidence","authors":"E. Robert, H. A. Al-Hashmi, A. Al-Mehaidib, K. Alsarraf, M. Al-Turaiki, W. Aldekhail, W. Al-Herz, A. Alkhabaz, Khalid O. Bawakid, A. Elghoudi, M. El Hodhod, Ali A. Hussain, N. Kamal, L. T. Goronfolah, B. Nasrallah, K. Sengupta, I. Broekaert, M. Domellöf, F. Indrio, A. Lapillonne, C. Pienar, C. Ribes-Koninckx, R. Shamir, H. Szajewska, N. Thapar, R. A. Thomassen, E. Verduci, C. West, Y. Vandenplas","doi":"10.3389/falgy.2024.1348769","DOIUrl":"https://doi.org/10.3389/falgy.2024.1348769","url":null,"abstract":"The diagnosis and management of cow's milk allergy (CMA) is a topic of debate and controversy. Our aim was to compare the opinions of expert groups from the Middle East (n = 14) and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (n = 13).These Expert groups voted on statements that were developed by the ESPGHAN group and published in a recent position paper. The voting outcome was compared.Overall, there was consensus amongst both groups of experts. Experts agreed that symptoms of crying, irritability and colic, as single manifestation, are not suggestive of CMA. They agreed that amino-acid based formula (AAF) should be reserved for severe cases (e.g., malnutrition and anaphylaxis) and that there is insufficient evidence to recommend a step-down approach. There was no unanimous consensus on the statement that a cow's milk based extensively hydrolysed formula (eHF) should be the first choice as a diagnostic elimination diet in mild/moderate cases. Although the statements regarding the role for hydrolysed rice formula as a diagnostic and therapeutic elimination diet were accepted, 3/27 disagreed. The votes regarding soy formula highlight the differences in opinion in the role of soy protein in CMA dietary treatment. Generally, soy-based formula is seldom available in the Middle-East region. All ESPGHAN experts agreed that there is insufficient evidence that the addition of probiotics, prebiotics and synbiotics increase the efficacy of elimination diets regarding CMA symptoms (despite other benefits such as decrease of infections and antibiotic intake), whereas 3/14 of the Middle East group thought there was sufficient evidence.Differences in voting are related to geographical, cultural and other conditions, such as cost and availability. This emphasizes the need to develop region-specific guidelines considering social and cultural conditions, and to perform further research in this area.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141345546","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 : 2024-06-11DOI: 10.3389/falgy.2024.1389669
Kameryn N. Furiness, Yasmeen S. El Ansari, Hans C. Oettgen, C. Kanagaratham
Food allergy, a group of adverse immune responses to normally innocuous food protein antigens, is an increasingly prevalent public health issue. The most common form is IgE-mediated food allergy in which food antigen-induced crosslinking of the high-affinity IgE-receptor, FcεRI, on the surface of mast cells triggers the release of inflammatory mediators that contribute to a wide range of clinical manifestations, including systemic anaphylaxis. Mast cells also play a critical function in adaptive immunity to foods, acting as adjuvants for food-antigen driven Th2 cell responses. While the diagnosis and treatment of food allergy has improved in recent years, no curative treatments are currently available. However, there is emerging evidence to suggest that both allergen-specific IgA and IgG antibodies can counter the activating effects of IgE antibodies on mast cells. Most notably, both antigen-specific IgA and IgG antibodies are induced in the course of oral immunotherapy. In this review, we highlight the role of mast cells in food allergy, both as inducers of immediate hypersensitivity reactions and as adjuvants for type 2 adaptive immune responses. Furthermore, we summarize current understanding of the immunomodulatory effects of antigen-specific IgA and IgG antibodies on IgE-induced mast cell activation and effector function. A more comprehensive understanding of the regulatory role of IgA and IgG in food allergy may provide insights into physiologic regulation of immune responses to ingested antigens and could seed novel strategies to treat allergic disease.
食物过敏是对通常无害的食物蛋白抗原产生的一组不良免疫反应,是一个日益普遍的公共健康问题。最常见的食物过敏形式是 IgE 介导的食物过敏,即食物抗原诱导肥大细胞表面的高亲和性 IgE 受体 FcεRI 交联,引发炎症介质的释放,导致多种临床表现,包括全身性过敏性休克。肥大细胞在对食物的适应性免疫中也发挥着关键作用,是食物抗原驱动的 Th2 细胞反应的佐剂。虽然近年来食物过敏的诊断和治疗有所改善,但目前还没有治疗方法。不过,有新的证据表明,过敏原特异性 IgA 和 IgG 抗体可以抵消 IgE 抗体对肥大细胞的激活作用。最值得注意的是,在口服免疫疗法过程中,抗原特异性 IgA 和 IgG 抗体都会被诱导。在这篇综述中,我们强调了肥大细胞在食物过敏中的作用,它既是即刻超敏反应的诱导物,也是 2 型适应性免疫反应的佐剂。此外,我们还总结了目前对抗原特异性 IgA 和 IgG 抗体对 IgE 诱导的肥大细胞活化和效应功能的免疫调节作用的认识。更全面地了解 IgA 和 IgG 在食物过敏中的调控作用,有助于深入了解摄入抗原对免疫反应的生理调控,并为过敏性疾病的治疗提供新策略。
{"title":"Allergen-specific IgA and IgG antibodies as inhibitors of mast cell function in food allergy","authors":"Kameryn N. Furiness, Yasmeen S. El Ansari, Hans C. Oettgen, C. Kanagaratham","doi":"10.3389/falgy.2024.1389669","DOIUrl":"https://doi.org/10.3389/falgy.2024.1389669","url":null,"abstract":"Food allergy, a group of adverse immune responses to normally innocuous food protein antigens, is an increasingly prevalent public health issue. The most common form is IgE-mediated food allergy in which food antigen-induced crosslinking of the high-affinity IgE-receptor, FcεRI, on the surface of mast cells triggers the release of inflammatory mediators that contribute to a wide range of clinical manifestations, including systemic anaphylaxis. Mast cells also play a critical function in adaptive immunity to foods, acting as adjuvants for food-antigen driven Th2 cell responses. While the diagnosis and treatment of food allergy has improved in recent years, no curative treatments are currently available. However, there is emerging evidence to suggest that both allergen-specific IgA and IgG antibodies can counter the activating effects of IgE antibodies on mast cells. Most notably, both antigen-specific IgA and IgG antibodies are induced in the course of oral immunotherapy. In this review, we highlight the role of mast cells in food allergy, both as inducers of immediate hypersensitivity reactions and as adjuvants for type 2 adaptive immune responses. Furthermore, we summarize current understanding of the immunomodulatory effects of antigen-specific IgA and IgG antibodies on IgE-induced mast cell activation and effector function. A more comprehensive understanding of the regulatory role of IgA and IgG in food allergy may provide insights into physiologic regulation of immune responses to ingested antigens and could seed novel strategies to treat allergic disease.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141358366","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 : 2024-06-06DOI: 10.3389/falgy.2024.1360073
E. J. J. Kallen, P. M. J. Welsing, J. M. Löwik, R. van Ree, A. Knulst, T. M. Le
Birch pollen–related food allergy (BPFA) is the most common type of food allergy in birch-endemic areas such as Western and Central Europe. Currently, there is no treatment available for BPFA. Due to the cross-reactivity between birch pollen and a range of implicated plant foods, birch pollen allergen immunotherapy (AIT) may be effective in the treatment of BPFA. In this study, we systematically evaluate the effectiveness of birch pollen–specific subcutaneous or sublingual immunotherapy in treating BPFA.A search was performed in the PubMed, Embase, and Cochrane libraries. Studies were independently screened by two reviewers against predefined eligibility criteria. The outcomes of interest were changes in (1) severity of symptoms during food challenge, (2) eliciting dose (ED), and (3) food allergy quality of life (FA-QoL). The validity of the selected articles was assessed using the revised Cochrane risk of bias tool. We focused on studies with the lowest risk of bias and considered studies with a high risk of bias as supportive. Data were descriptively summarized.Ten studies were selected that included 475 patients in total. Seven studies were categorized into “high risk of bias” and three into “moderate risk of bias.” The three moderate risk of bias studies, with a total of 98 patients, reported on severity of symptoms during challenge and on the ED. All three studies had a control group. Compared to the control group, improvement in severity of symptoms was observed during challenge in two out of the three studies and on the eliciting dose in one out of three. Only one study investigated the effect of birch pollen AIT on FA-QoL, showing that there was no significant difference between patients receiving subcutaneous immunotherapy or a placebo. Of the seven supportive studies, four had a control group and of those, three showed improvement on both severity of symptoms and ED. None of the supportive studies investigated the effect of the therapy on FA-QoL.This systematic review shows that there is not enough evidence to draw firm conclusions about the effect of AIT on BPFA. Future research is warranted that uses robust clinical studies that include long-term effects, QoL, and multiple BPFA-related foods.
{"title":"The effect of subcutaneous and sublingual birch pollen immunotherapy on birch pollen–related food allergy: a systematic review","authors":"E. J. J. Kallen, P. M. J. Welsing, J. M. Löwik, R. van Ree, A. Knulst, T. M. Le","doi":"10.3389/falgy.2024.1360073","DOIUrl":"https://doi.org/10.3389/falgy.2024.1360073","url":null,"abstract":"Birch pollen–related food allergy (BPFA) is the most common type of food allergy in birch-endemic areas such as Western and Central Europe. Currently, there is no treatment available for BPFA. Due to the cross-reactivity between birch pollen and a range of implicated plant foods, birch pollen allergen immunotherapy (AIT) may be effective in the treatment of BPFA. In this study, we systematically evaluate the effectiveness of birch pollen–specific subcutaneous or sublingual immunotherapy in treating BPFA.A search was performed in the PubMed, Embase, and Cochrane libraries. Studies were independently screened by two reviewers against predefined eligibility criteria. The outcomes of interest were changes in (1) severity of symptoms during food challenge, (2) eliciting dose (ED), and (3) food allergy quality of life (FA-QoL). The validity of the selected articles was assessed using the revised Cochrane risk of bias tool. We focused on studies with the lowest risk of bias and considered studies with a high risk of bias as supportive. Data were descriptively summarized.Ten studies were selected that included 475 patients in total. Seven studies were categorized into “high risk of bias” and three into “moderate risk of bias.” The three moderate risk of bias studies, with a total of 98 patients, reported on severity of symptoms during challenge and on the ED. All three studies had a control group. Compared to the control group, improvement in severity of symptoms was observed during challenge in two out of the three studies and on the eliciting dose in one out of three. Only one study investigated the effect of birch pollen AIT on FA-QoL, showing that there was no significant difference between patients receiving subcutaneous immunotherapy or a placebo. Of the seven supportive studies, four had a control group and of those, three showed improvement on both severity of symptoms and ED. None of the supportive studies investigated the effect of the therapy on FA-QoL.This systematic review shows that there is not enough evidence to draw firm conclusions about the effect of AIT on BPFA. Future research is warranted that uses robust clinical studies that include long-term effects, QoL, and multiple BPFA-related foods.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141380734","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}