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      The allergenic activity and clinical impact of individual IgE-antibody binding molecules from indoor allergen sources

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          Abstract

          A large number of allergens have been discovered but we know little about their potential to induce inflammation (allergenic activity) and symptoms. Nowadays, the clinical importance of allergens is determined by the frequency and intensity of their IgE antibody binding (allergenicity). This is a rather limited parameter considering the development of experimental allergology in the last 20 years and the criteria that support personalized medicine. Now it is known that some allergens, in addition to their IgE antibody binding properties, can induce inflammation through non IgE mediated pathways, which can increase their allergenic activity. There are several ways to evaluate the allergenic activity, among them the provocation tests, the demonstration of non-IgE mediated pathways of inflammation, case control studies of IgE-binding frequencies, and animal models of respiratory allergy. In this review we have explored the current status of basic and clinical research on allergenic activity of indoor allergens and confirm that, for most of them, this important property has not been investigated. However, during recent years important advances have been made in the field, and we conclude that for at least the following, allergenic activity has been demonstrated: Der p 1, Der p 2, Der p 5 and Blo t 5 from HDMs; Per a 10 from P. americana; Asp f 1, Asp f 2, Asp f 3, Asp f 4 and Asp f 6 from A. fumigatus; Mala s 8 and Mala s 13 from M. sympodialis; Alt a 1 from A. alternata; Pen c 13 from P. chrysogenum; Fel d 1 from cats; Can f 1, Can f 2, Can f 3, Can f 4 and Can f 5 from dogs; Mus m 1 from mice and Bos d 2 from cows. Defining the allergenic activity of other indoor IgE antibody binding molecules is necessary for a precision-medicine-oriented management of allergic diseases.

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          Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions.

          House dust mite (HDM) allergens are important factors in the increasing prevalence of asthma. The lung epithelium forms a barrier that allergens must cross before they can cause sensitization. However, the mechanisms involved are unknown. Here we show that the cysteine proteinase allergen Der p 1 from fecal pellets of the HDM Dermatophagoides pteronyssinus causes disruption of intercellular tight junctions (TJs), which are the principal components of the epithelial paracellular permeability barrier. In confluent airway epithelial cells, Der p 1 led to cleavage of the TJ adhesion protein occludin. Cleavage was attenuated by antipain, but not by inhibitors of serine, aspartic, or matrix metalloproteinases. Putative Der p 1 cleavage sites were found in peptides from an extracellular domain of occludin and in the TJ adhesion protein claudin-1. TJ breakdown nonspecifically increased epithelial permeability, allowing Der p 1 to cross the epithelial barrier. Thus, transepithelial movement of Der p 1 to dendritic antigen-presenting cells via the paracellular pathway may be promoted by the allergen's own proteolytic activity. These results suggest that opening of TJs by environmental proteinases may be the initial step in the development of asthma to a variety of allergens.
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            Indoor Environmental Exposures and Exacerbation of Asthma: An Update to the 2000 Review by the Institute of Medicine

            Background: Previous research has found relationships between specific indoor environmental exposures and exacerbation of asthma. Objectives: In this review we provide an updated summary of knowledge from the scientific literature on indoor exposures and exacerbation of asthma. Methods: Peer-reviewed articles published from 2000 to 2013 on indoor exposures and exacerbation of asthma were identified through PubMed, from reference lists, and from authors’ files. Articles that focused on modifiable indoor exposures in relation to frequency or severity of exacerbation of asthma were selected for review. Research findings were reviewed and summarized with consideration of the strength of the evidence. Results: Sixty-nine eligible articles were included. Major changed conclusions include a causal relationship with exacerbation for indoor dampness or dampness-related agents (in children); associations with exacerbation for dampness or dampness-related agents (in adults), endotoxin, and environmental tobacco smoke (in preschool children); and limited or suggestive evidence for association with exacerbation for indoor culturable Penicillium or total fungi, nitrogen dioxide, rodents (nonoccupational), feather/down pillows (protective relative to synthetic bedding), and (regardless of specific sensitization) dust mite, cockroach, dog, and dampness-related agents. Discussion: This review, incorporating evidence reported since 2000, increases the strength of evidence linking many indoor factors to the exacerbation of asthma. Conclusions should be considered provisional until all available evidence is examined more thoroughly. Conclusion: Multiple indoor exposures, especially dampness-related agents, merit increased attention to prevent exacerbation of asthma, possibly even in nonsensitized individuals. Additional research to establish causality and evaluate interventions is needed for these and other indoor exposures. Citation: Kanchongkittiphon W, Mendell MJ, Gaffin JM, Wang G, Phipatanakul W. 2015. Indoor environmental exposures and exacerbation of asthma: an update to the 2000 review by the Institute of Medicine. Environ Health Perspect 123:6–20; http://dx.doi.org/10.1289/ehp.1307922
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              Environmental determinants of allergy and asthma in early life.

              Allergic disease prevalence has increased significantly in recent decades. Primary prevention efforts are being guided by study of the exposome (or collective environmental exposures beginning during the prenatal period) to identify modifiable factors that affect allergic disease risk. In this review we explore the evidence supporting a relationship between key components of the external exposome in the prenatal and early-life periods and their effect on atopy development focused on microbial, allergen, and air pollution exposures. The abundance and diversity of microbial exposures during the first months and years of life have been linked with risk of allergic sensitization and disease. Indoor environmental allergen exposure during early life can also affect disease development, depending on the allergen type, dose, and timing of exposure. Recent evidence supports the role of ambient air pollution in allergic disease inception. The lack of clarity in the literature surrounding the relationship between environment and atopy reflects the complex interplay between cumulative environmental factors and genetic susceptibility, such that no one factor dictates disease development in all subjects. Understanding the effect of the summation of environmental exposures throughout a child's development is needed to identify cost-effective interventions that reduce atopy risk in children.
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                Author and article information

                Contributors
                Journal
                World Allergy Organ J
                World Allergy Organ J
                The World Allergy Organization Journal
                World Allergy Organization
                1939-4551
                29 April 2020
                May 2020
                29 April 2020
                : 13
                : 5
                : 100118
                Affiliations
                [a ]Institute for Immunological Research, University of Cartagena, Cartagena, Colombia
                [b ]Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
                [c ]NRC Institute of Immunology FMBA of Russia, Moscow, Russian Federation
                [d ]Indoor Biotechnologies, Inc. Charlottesville, VA, USA
                [e ]Inmunotek, Madrid, Spain and University of South Florida College of Medicine, Tampa, USA
                [f ]Allergy and Clinical Immunology Department, Centro Médico Docente La Trinidad, Caracas, Venezuela
                [g ]Department of Allergy & Immunology Hospital Quironsalud Bizkaia, Bilbao, Spain
                [h ]Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China
                [i ]Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
                [j ]Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil
                [k ]Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
                [l ]Department of Clinical Immunology and Allergy, Laboratory of Immunopathology, Sechenov First Moscow State Medical University, Moscow, Russia
                Author notes
                []Corresponding author. Institute for Immunological Research, University of Cartagena, Cartagena de Indias, Colombia. lcaraballog@ 123456unicartagena.edu.co
                Article
                S1939-4551(20)30021-1 100118
                10.1016/j.waojou.2020.100118
                7195550
                32373267
                f751b8a2-4415-4214-86b0-948141679589
                © 2020 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 13 January 2020
                : 27 March 2020
                : 30 March 2020
                Categories
                Article

                Immunology
                Immunology

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