Alexander Eggel, Luke F Pennington, Theodore S Jardetzky
The etiology of allergy is closely linked to type 2 inflammatory responses ultimately leading to the production of allergen-specific immunoglobulin E (IgE), a key driver of many allergic conditions. At a high level, initial allergen exposure disrupts epithelial integrity, triggering local inflammation via alarmins including IL-25, IL-33, and TSLP, which activate type 2 innate lymphoid cells as well as other immune cells to secrete type 2 cytokines IL-4, IL-5 and IL-13, promoting Th2 cell development and eosinophil recruitment. Th2 cell dependent B cell activation promotes the production of allergen-specific IgE, which stably binds to basophils and mast cells. Rapid degranulation of these cells upon allergen re-exposure leads to allergic symptoms. Recent advances in our understanding of the molecular and cellular mechanisms underlying allergic pathophysiology have significantly shaped the development of therapeutic intervention strategies. In this review, we highlight key therapeutic targets within the allergic cascade with a particular focus on past, current and future treatment approaches using monoclonal antibodies. Specific targeting of alarmins, type 2 cytokines and IgE has shown varying degrees of clinical benefit in different allergic indications including asthma, chronic spontaneous urticaria, atopic dermatitis, chronic rhinosinusitis with nasal polyps, food allergies and eosinophilic esophagitis. While multiple therapeutic antibodies have been approved for clinical use, scientists are still working on ways to improve on current treatment approaches. Here, we provide context to understand therapeutic targeting strategies and their limitations, discussing both knowledge gaps and promising future directions to enhancing clinical efficacy in allergic disease management.
{"title":"Therapeutic monoclonal antibodies in allergy: Targeting IgE, cytokine, and alarmin pathways.","authors":"Alexander Eggel, Luke F Pennington, Theodore S Jardetzky","doi":"10.1111/imr.13380","DOIUrl":"https://doi.org/10.1111/imr.13380","url":null,"abstract":"<p><p>The etiology of allergy is closely linked to type 2 inflammatory responses ultimately leading to the production of allergen-specific immunoglobulin E (IgE), a key driver of many allergic conditions. At a high level, initial allergen exposure disrupts epithelial integrity, triggering local inflammation via alarmins including IL-25, IL-33, and TSLP, which activate type 2 innate lymphoid cells as well as other immune cells to secrete type 2 cytokines IL-4, IL-5 and IL-13, promoting Th2 cell development and eosinophil recruitment. Th2 cell dependent B cell activation promotes the production of allergen-specific IgE, which stably binds to basophils and mast cells. Rapid degranulation of these cells upon allergen re-exposure leads to allergic symptoms. Recent advances in our understanding of the molecular and cellular mechanisms underlying allergic pathophysiology have significantly shaped the development of therapeutic intervention strategies. In this review, we highlight key therapeutic targets within the allergic cascade with a particular focus on past, current and future treatment approaches using monoclonal antibodies. Specific targeting of alarmins, type 2 cytokines and IgE has shown varying degrees of clinical benefit in different allergic indications including asthma, chronic spontaneous urticaria, atopic dermatitis, chronic rhinosinusitis with nasal polyps, food allergies and eosinophilic esophagitis. While multiple therapeutic antibodies have been approved for clinical use, scientists are still working on ways to improve on current treatment approaches. Here, we provide context to understand therapeutic targeting strategies and their limitations, discussing both knowledge gaps and promising future directions to enhancing clinical efficacy in allergic disease management.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mihaela Chisca, Jean-David Larouche, Qi Xing, George Kassiotis
The human genome harbors hundreds of thousands of integrations of ancient retroviruses, amassed over millions of years of evolution. To reduce further amplification in the genome, the host prevents transcription of these now endogenous retroviruses (ERVs) through epigenetic repression and, with evolutionary time, ERVs are incapacitated by accumulating mutations and deletions. However, several members of recently endogenized ERV groups still retain the capacity to produce viral RNA, retroviral proteins, and higher order structures, including virions. The retention of viral characteristics, combined with the reversible nature of epigenetic repression, particularly as seen in cancer, allow for immunologically unanticipated ERV expression, perceived by the adaptive immune system as a genuine retroviral infection, to which it has to respond. Accordingly, antibodies reactive with ERV antigens have been detected in diverse disorders and, occasionally, in healthy individuals. Although they are part of self, the retroviral legacy of ERV antigens, and association with and, possibly, causation of disease states may set them apart from typical self-antigens. Consequently, the pathogenic or, indeed, host-protective capacity of antibodies targeting ERV antigens is likely to be context-dependent. Here, we review the immunogenicity of typical ERV proteins, with emphasis on the antibody response and its potential disease implications.
{"title":"Antibodies against endogenous retroviruses.","authors":"Mihaela Chisca, Jean-David Larouche, Qi Xing, George Kassiotis","doi":"10.1111/imr.13378","DOIUrl":"https://doi.org/10.1111/imr.13378","url":null,"abstract":"<p><p>The human genome harbors hundreds of thousands of integrations of ancient retroviruses, amassed over millions of years of evolution. To reduce further amplification in the genome, the host prevents transcription of these now endogenous retroviruses (ERVs) through epigenetic repression and, with evolutionary time, ERVs are incapacitated by accumulating mutations and deletions. However, several members of recently endogenized ERV groups still retain the capacity to produce viral RNA, retroviral proteins, and higher order structures, including virions. The retention of viral characteristics, combined with the reversible nature of epigenetic repression, particularly as seen in cancer, allow for immunologically unanticipated ERV expression, perceived by the adaptive immune system as a genuine retroviral infection, to which it has to respond. Accordingly, antibodies reactive with ERV antigens have been detected in diverse disorders and, occasionally, in healthy individuals. Although they are part of self, the retroviral legacy of ERV antigens, and association with and, possibly, causation of disease states may set them apart from typical self-antigens. Consequently, the pathogenic or, indeed, host-protective capacity of antibodies targeting ERV antigens is likely to be context-dependent. Here, we review the immunogenicity of typical ERV proteins, with emphasis on the antibody response and its potential disease implications.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Food allergy is classically characterized by an inappropriate type-2 immune response to allergenic food antigens. However, how allergens are detected and how that detection leads to the initiation of allergic immunity is poorly understood. In addition to the gastrointestinal tract, the barrier epithelium of the skin may also act as a site of food allergen sensitization. These barrier epithelia are densely innervated by sensory neurons, which respond to diverse physical environmental stimuli. Recent findings suggest that sensory neurons can directly detect a broad array of immunogens, including allergens, triggering sensory responses and the release of neuropeptides that influence immune cell function. Reciprocally, immune mediators modulate the activation or responsiveness of sensory neurons, forming neuroimmune feedback loops that may impact allergic immune responses. By utilizing cutaneous allergen exposure as a model, this review explores the pivotal role of sensory neurons in allergen detection and their dynamic bidirectional communication with the immune system, which ultimately orchestrates the type-2 immune response. Furthermore, it sheds light on how peripheral signals are integrated within the central nervous system to coordinate hallmark features of allergic reactions. Drawing from this emerging evidence, we propose that atopy arises from a dysregulated neuroimmune circuit.
{"title":"Sensory sentinels: Neuroimmune detection and food allergy.","authors":"Peri R Matatia, Elena Christian, Caroline L Sokol","doi":"10.1111/imr.13375","DOIUrl":"https://doi.org/10.1111/imr.13375","url":null,"abstract":"<p><p>Food allergy is classically characterized by an inappropriate type-2 immune response to allergenic food antigens. However, how allergens are detected and how that detection leads to the initiation of allergic immunity is poorly understood. In addition to the gastrointestinal tract, the barrier epithelium of the skin may also act as a site of food allergen sensitization. These barrier epithelia are densely innervated by sensory neurons, which respond to diverse physical environmental stimuli. Recent findings suggest that sensory neurons can directly detect a broad array of immunogens, including allergens, triggering sensory responses and the release of neuropeptides that influence immune cell function. Reciprocally, immune mediators modulate the activation or responsiveness of sensory neurons, forming neuroimmune feedback loops that may impact allergic immune responses. By utilizing cutaneous allergen exposure as a model, this review explores the pivotal role of sensory neurons in allergen detection and their dynamic bidirectional communication with the immune system, which ultimately orchestrates the type-2 immune response. Furthermore, it sheds light on how peripheral signals are integrated within the central nervous system to coordinate hallmark features of allergic reactions. Drawing from this emerging evidence, we propose that atopy arises from a dysregulated neuroimmune circuit.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Food allergies occur due to a lack of tolerance to the proteins found in foods. While IgE- and non-IgE-mediated food allergies have different clinical manifestations, epidemiology, pathophysiology, and management, they share dysregulated T cell responses. Recent studies have shed light on the contributions of different T cell subsets to the development and persistence of different food allergic diseases. This review discusses the role of T cells in both IgE- and non-IgE-mediated food allergies and considers the potential future investigations in this context.
食物过敏的发生是由于对食物中的蛋白质缺乏耐受性。虽然IgE介导的食物过敏和非IgE介导的食物过敏在临床表现、流行病学、病理生理学和治疗方法上各不相同,但它们都存在T细胞反应失调的问题。最近的研究揭示了不同的 T 细胞亚群对不同食物过敏性疾病的发生和持续存在的作用。本综述讨论了 T 细胞在 IgE 和非 IgE 介导的食物过敏中的作用,并探讨了在此背景下未来可能开展的研究。
{"title":"Contribution of T cell subsets to different food allergic diseases.","authors":"Lisa Hung, Brianna Zientara, M Cecilia Berin","doi":"10.1111/imr.13368","DOIUrl":"https://doi.org/10.1111/imr.13368","url":null,"abstract":"<p><p>Food allergies occur due to a lack of tolerance to the proteins found in foods. While IgE- and non-IgE-mediated food allergies have different clinical manifestations, epidemiology, pathophysiology, and management, they share dysregulated T cell responses. Recent studies have shed light on the contributions of different T cell subsets to the development and persistence of different food allergic diseases. This review discusses the role of T cells in both IgE- and non-IgE-mediated food allergies and considers the potential future investigations in this context.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mariana C G Miranda-Waldetario, Maria A Curotto de Lafaille
Immune tolerance to foods develops in the intestine upon food ingestion and is essential to prevent IgE-mediated food allergy and gut inflammation. In homeostasis, the intestine is a tolerogenic environment that favors the formation of food-specific Foxp3+ regulatory T cells. A tolerogenic intestinal environment depends on colonization by diverse microbiota and exposure to solid foods at a critical period in early life. These early immune responses lead to the induction of antigen-specific Foxp3+ regulatory T cells in draining mesenteric lymph nodes. These peripherally induced regulatory cells circulate and seed the lamina propria of the gut, exerting suppressive function systemically and locally in the intestine. Successful establishment of a tolerogenic intestinal environment in early life sets the stage for oral tolerance to new antigens in adult life.
摄入食物后,肠道会产生对食物的免疫耐受,这对预防 IgE 介导的食物过敏和肠道炎症至关重要。在平衡状态下,肠道是一个产生耐受性的环境,有利于食物特异性 Foxp3+ 调节性 T 细胞的形成。耐受性肠道环境取决于多种微生物群的定植以及在生命早期的关键时期接触固体食物。这些早期免疫反应会在引流的肠系膜淋巴结中诱导抗原特异性 Foxp3+ 调节性 T 细胞。这些外周诱导的调节性细胞在肠道固有层循环和播种,在全身和肠道局部发挥抑制功能。早期肠道耐受环境的成功建立为成年后对新抗原的口服耐受奠定了基础。
{"title":"Oral tolerance to dietary antigens and Foxp3<sup>+</sup> regulatory T cells.","authors":"Mariana C G Miranda-Waldetario, Maria A Curotto de Lafaille","doi":"10.1111/imr.13370","DOIUrl":"10.1111/imr.13370","url":null,"abstract":"<p><p>Immune tolerance to foods develops in the intestine upon food ingestion and is essential to prevent IgE-mediated food allergy and gut inflammation. In homeostasis, the intestine is a tolerogenic environment that favors the formation of food-specific Foxp3<sup>+</sup> regulatory T cells. A tolerogenic intestinal environment depends on colonization by diverse microbiota and exposure to solid foods at a critical period in early life. These early immune responses lead to the induction of antigen-specific Foxp3<sup>+</sup> regulatory T cells in draining mesenteric lymph nodes. These peripherally induced regulatory cells circulate and seed the lamina propria of the gut, exerting suppressive function systemically and locally in the intestine. Successful establishment of a tolerogenic intestinal environment in early life sets the stage for oral tolerance to new antigens in adult life.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emily R Siniscalco, Adam Williams, Stephanie C Eisenbarth
The increasing prevalence of food allergy and related pathologies in recent years has underscored the need to understand the factors affecting adverse reactions to food. Food allergy is caused when food-specific IgE triggers the release of histamine from mast cells. However, other food-specific antibody isotypes exist as well, including IgG and IgA. IgA is the main antibody isotype in the gut and mediates noninflammatory reactions to toxins, commensal bacteria, and food antigens. It has also been thought to induce tolerance to food, thus antagonizing the role of food-specific IgE. However, this has remained unclear as food-specific IgA generation is poorly understood. Particularly, the location of IgA induction, the role of T cell help, and the fates of food-specific B cells remain elusive. In this review, we outline what is known about food-specific IgA induction and highlight areas requiring further study. We also explore how knowledge of food-specific IgA induction can be informed by and subsequently contribute to our overall knowledge of gut immunity.
近年来,食物过敏和相关病症的发病率不断上升,这凸显了了解影响食物不良反应因素的必要性。食物特异性 IgE 触发肥大细胞释放组胺,从而引起食物过敏。不过,也存在其他食物特异性抗体异型,包括 IgG 和 IgA。IgA 是肠道中的主要抗体同工型,可介导对毒素、共生细菌和食物抗原的非炎症反应。人们还认为 IgA 能诱导对食物的耐受性,从而抵消食物特异性 IgE 的作用。然而,由于人们对食物特异性 IgA 的产生还知之甚少,因此这一点仍不清楚。特别是,IgA 诱导的位置、T 细胞帮助的作用以及食物特异性 B 细胞的命运仍然难以捉摸。在这篇综述中,我们概述了有关食物特异性 IgA 诱导的已知知识,并强调了需要进一步研究的领域。我们还探讨了如何通过食物特异性 IgA 诱导的知识来了解肠道免疫的整体知识,进而为这些知识做出贡献。
{"title":"All roads lead to IgA: Mapping the many pathways of IgA induction in the gut.","authors":"Emily R Siniscalco, Adam Williams, Stephanie C Eisenbarth","doi":"10.1111/imr.13369","DOIUrl":"https://doi.org/10.1111/imr.13369","url":null,"abstract":"<p><p>The increasing prevalence of food allergy and related pathologies in recent years has underscored the need to understand the factors affecting adverse reactions to food. Food allergy is caused when food-specific IgE triggers the release of histamine from mast cells. However, other food-specific antibody isotypes exist as well, including IgG and IgA. IgA is the main antibody isotype in the gut and mediates noninflammatory reactions to toxins, commensal bacteria, and food antigens. It has also been thought to induce tolerance to food, thus antagonizing the role of food-specific IgE. However, this has remained unclear as food-specific IgA generation is poorly understood. Particularly, the location of IgA induction, the role of T cell help, and the fates of food-specific B cells remain elusive. In this review, we outline what is known about food-specific IgA induction and highlight areas requiring further study. We also explore how knowledge of food-specific IgA induction can be informed by and subsequently contribute to our overall knowledge of gut immunity.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rita Nocerino, Laura Carucci, Serena Coppola, Franca Oglio, Antonio Masino, Alessandra Agizza, Lorella Paparo, Roberto Berni Canani
Cow milk protein allergy (CMPA) is one of the most common food allergies in the pediatric age worldwide. Prevalence, persistence, and severity of this condition are on the rise, with a negative impact on the health-related quality of life of the patients and families and on the costs related to its management. Another relevant issue is that CMPA in early life may be the first stage of the "allergic march," leading to the occurrence of other atopic manifestations later in life, especially asthma, atopic eczema, urticaria, and rhinoconjunctivitis. Thus, "disease modification" options that are able to modulate the disease course of pediatric patients affected by CMPA would be very welcomed by affected families and healthcare systems. In this review, we report the most relevant progress on this topic.
{"title":"The journey toward disease modification in cow milk protein allergy.","authors":"Rita Nocerino, Laura Carucci, Serena Coppola, Franca Oglio, Antonio Masino, Alessandra Agizza, Lorella Paparo, Roberto Berni Canani","doi":"10.1111/imr.13372","DOIUrl":"https://doi.org/10.1111/imr.13372","url":null,"abstract":"<p><p>Cow milk protein allergy (CMPA) is one of the most common food allergies in the pediatric age worldwide. Prevalence, persistence, and severity of this condition are on the rise, with a negative impact on the health-related quality of life of the patients and families and on the costs related to its management. Another relevant issue is that CMPA in early life may be the first stage of the \"allergic march,\" leading to the occurrence of other atopic manifestations later in life, especially asthma, atopic eczema, urticaria, and rhinoconjunctivitis. Thus, \"disease modification\" options that are able to modulate the disease course of pediatric patients affected by CMPA would be very welcomed by affected families and healthcare systems. In this review, we report the most relevant progress on this topic.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Despite the near ubiquitous presence of Ig-based antibodies in vertebrates, IgE is unique to mammals. How and why it emerged remains mysterious. IgE expression is greatly constrained compared to other IgH isotypes. While other IgH isotypes are relatively abundant, soluble IgE has a truncated half-life, and IgE plasma cells are mostly short-lived. Despite its rarity, IgE is consequential and can trigger life-threatening anaphylaxis. IgE production reflects a dynamic steady state with IgG memory B cells feeding short-lived IgE production. Emerging evidence suggests that IgE may also potentially be produced in longer-lived plasma cells as well, perhaps as an aberrancy stemming from its evolutionary roots from an antibody isotype that likely functioned more like IgG. As a late derivative of an ancient systemic antibody system, the benefits of IgE in mammals likely stems from the antibody system's adaptive recognition and response capability. However, the tendency for massive, systemic, and long-lived production, common to IgH isotypes like IgG, were likely not a good fit for IgE. The evolutionary derivation of IgE from an antibody system that for millions of years was good at antigen de-sensitization to now functioning as a highly specialized antigen-sensitization function required heavy restrictions on antibody production-insufficiency of which may contribute to allergic disease.
{"title":"Whence and wherefore IgE?","authors":"Rifat S Rahman, Duane R Wesemann","doi":"10.1111/imr.13373","DOIUrl":"https://doi.org/10.1111/imr.13373","url":null,"abstract":"<p><p>Despite the near ubiquitous presence of Ig-based antibodies in vertebrates, IgE is unique to mammals. How and why it emerged remains mysterious. IgE expression is greatly constrained compared to other IgH isotypes. While other IgH isotypes are relatively abundant, soluble IgE has a truncated half-life, and IgE plasma cells are mostly short-lived. Despite its rarity, IgE is consequential and can trigger life-threatening anaphylaxis. IgE production reflects a dynamic steady state with IgG memory B cells feeding short-lived IgE production. Emerging evidence suggests that IgE may also potentially be produced in longer-lived plasma cells as well, perhaps as an aberrancy stemming from its evolutionary roots from an antibody isotype that likely functioned more like IgG. As a late derivative of an ancient systemic antibody system, the benefits of IgE in mammals likely stems from the antibody system's adaptive recognition and response capability. However, the tendency for massive, systemic, and long-lived production, common to IgH isotypes like IgG, were likely not a good fit for IgE. The evolutionary derivation of IgE from an antibody system that for millions of years was good at antigen de-sensitization to now functioning as a highly specialized antigen-sensitization function required heavy restrictions on antibody production-insufficiency of which may contribute to allergic disease.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hind Hussein, Samuel Van Remoortel, Guy E Boeckxstaens
Irritable bowel syndrome (IBS) is a chronic gastrointestinal condition associated with altered bowel habits and recurrent abdominal pain, often triggered by food intake. Current treatments focus on improving stool pattern, but effective treatments for pain in IBS are still lacking due to our limited understanding of pathophysiological mechanisms. Visceral hypersensitivity (VHS), or abnormal visceral pain perception, underlies abdominal pain development in IBS, and mast cell activation has been shown to play an important role in the development of VHS. Our work recently revealed that abdominal pain in response to food intake is induced by the sensitization of colonic pain-sensing neurons by histamine produced by activated mast cells following a local IgE response to food. In this review, we summarize the current knowledge on abdominal pain and VHS pathophysiology in IBS, we outline the work leading to the discovery of the role of histamine in abdominal pain, and we introduce antihistamines as a novel treatment option to manage chronic abdominal pain in patients with IBS.
{"title":"Irritable bowel syndrome: When food is a pain in the gut.","authors":"Hind Hussein, Samuel Van Remoortel, Guy E Boeckxstaens","doi":"10.1111/imr.13374","DOIUrl":"https://doi.org/10.1111/imr.13374","url":null,"abstract":"<p><p>Irritable bowel syndrome (IBS) is a chronic gastrointestinal condition associated with altered bowel habits and recurrent abdominal pain, often triggered by food intake. Current treatments focus on improving stool pattern, but effective treatments for pain in IBS are still lacking due to our limited understanding of pathophysiological mechanisms. Visceral hypersensitivity (VHS), or abnormal visceral pain perception, underlies abdominal pain development in IBS, and mast cell activation has been shown to play an important role in the development of VHS. Our work recently revealed that abdominal pain in response to food intake is induced by the sensitization of colonic pain-sensing neurons by histamine produced by activated mast cells following a local IgE response to food. In this review, we summarize the current knowledge on abdominal pain and VHS pathophysiology in IBS, we outline the work leading to the discovery of the role of histamine in abdominal pain, and we introduce antihistamines as a novel treatment option to manage chronic abdominal pain in patients with IBS.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pamela A Frischmeyer-Guerrerio, Fernanda D Young, Ozge N Aktas, Tamara Haque
The last few decades have seen striking changes in the field of food allergy. The prevalence of the disease has risen dramatically in many parts of the globe, and management of the condition has undergone major revision. While delayed introduction of common allergenic foods during infancy was advised for many years, the learning early about peanut allergy (LEAP) trial and other studies led to a major shift in infant feeding practices, with deliberate early introduction of these foods now recommended. Additionally, the Food and Drug Administration approved the first treatment for food allergy in 2020-a peanut oral immunotherapy (OIT) product that likely represents just the beginning of new immunotherapy-based and other treatments for food allergy. Our knowledge of the environmental and genetic factors contributing to the pathogenesis of food allergy has also undergone transformational advances. Here, we will discuss our efforts to improve the clinical care of patients with food allergy and our understanding of the immunological mechanisms contributing to this common disease.
{"title":"Insights into the clinical, immunologic, and genetic underpinnings of food allergy.","authors":"Pamela A Frischmeyer-Guerrerio, Fernanda D Young, Ozge N Aktas, Tamara Haque","doi":"10.1111/imr.13371","DOIUrl":"https://doi.org/10.1111/imr.13371","url":null,"abstract":"<p><p>The last few decades have seen striking changes in the field of food allergy. The prevalence of the disease has risen dramatically in many parts of the globe, and management of the condition has undergone major revision. While delayed introduction of common allergenic foods during infancy was advised for many years, the learning early about peanut allergy (LEAP) trial and other studies led to a major shift in infant feeding practices, with deliberate early introduction of these foods now recommended. Additionally, the Food and Drug Administration approved the first treatment for food allergy in 2020-a peanut oral immunotherapy (OIT) product that likely represents just the beginning of new immunotherapy-based and other treatments for food allergy. Our knowledge of the environmental and genetic factors contributing to the pathogenesis of food allergy has also undergone transformational advances. Here, we will discuss our efforts to improve the clinical care of patients with food allergy and our understanding of the immunological mechanisms contributing to this common disease.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}