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Molecular and Cellular Basis of Food Allergies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 52252

Special Issue Editor


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Guest Editor
NeuroAllergy Research Laboratory (NARL), School of Life and Environmental Sciences, Faculty of Science, Engineering and Built Environment, Waurn Ponds, VIC 3216, Australia
Interests: aerobiology; allergic asthma; allergy diagnostics; allergy immunotherapy reagents; cytokine signalling; epigenetics; food allergy; inhibitors of allergic reaction; inhibitors of Alzheimer’s disease; neuroscience; nutrition; pollen allergy; thunderstorm asthma
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Special Issue Information

Dear Colleagues,

Welcome to this Special Issue of Molecular Immunology Section of the International Journal of Molecular Sciences, on “Molecular and Cellular Basis of Food Allergies”.

Food allergens are all around us and for unsuspecting sufferers, when they are hidden in processed food, they can present a significant danger of a severe allergic reaction, which may prove fatal. Some studies are showing that the incidence of food allergies is on the rise, impacting children and adults alike. Some of the major food allergies include, but are not limited to eggs, nuts, milk and seafood. In addition, food allergens may present themselves in the environments we work in as inhalant allergens and thus may be seen as occupational allergies. Therefore, the molecular and cellular characterisation of food allergens, and food allergy itself, is a significant research area helping us to better understand the disease and prepare targeted novel reagents for its effective and specific diagnosis and treatment.

This Special Issue is aimed at presenting cutting edge research findings and reviews related to the molecular and cellular basis of food allergies and food allergy itself. In particular, the molecular cloning of food allergens, as well as their recombinant expression and immunological characterisation are significant first steps for preparing effective and specific reagents for the in vitro diagnosis of food allergies. Furthermore, B and T cell epitope mapping, coupled with site-directed in vitro mutagenesis, has been most useful for the preparation of recombinant hypoallergens, which may be useful for targeted therapy. Also, understanding the molecular and immunological basis of allergen cross-reactivity is important for assessing allergenic prevalence and accidental exposure to allergens. I have the pleasure of inviting both clinicians and research scientists in all relevant fields to submit their original research papers and relevant review articles to this significant Special Issue on food allergy. I look forward to your submissions and please accept my sincere thanks in advance for choosing to publish in the Molecular Immunology Section of the International Journal of Molecular Sciences.

Prof. Dr. Cenk Suphioglu
Guest Editor

Manuscript Submission Information

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Keywords

  • Food allergens
  • Food allergy
  • Allergic reaction
  • Occupational allergy
  • Allergens exposure
  • Immunology

Published Papers (8 papers)

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Research

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13 pages, 3248 KiB  
Article
Variation in Shrimp Allergens: Place of Origin Effects on Food Safety Assessment
by Ryley D. Dorney, Elecia B. Johnston, Shaymaviswanathan Karnaneedi, Thimo Ruethers, Sandip D. Kamath, Karthik Gopi, Debashish Mazumder, Jesmond Sammut, Dean Jerry, Nicholas A. Williamson, Shuai Nie and Andreas L. Lopata
Int. J. Mol. Sci. 2024, 25(8), 4531; https://doi.org/10.3390/ijms25084531 - 20 Apr 2024
Viewed by 992
Abstract
Due to the widespread use of shellfish ingredients in food products, accurate food labelling is urgently needed for consumers with shellfish allergies. Most crustacean allergen detection systems target the immunorecognition of the allergenic protein tropomyosin. However, this mode of detection may be affected [...] Read more.
Due to the widespread use of shellfish ingredients in food products, accurate food labelling is urgently needed for consumers with shellfish allergies. Most crustacean allergen detection systems target the immunorecognition of the allergenic protein tropomyosin. However, this mode of detection may be affected by an origin-dependent protein composition. This study determined if the geographic location of capture, or aquaculture, influenced the allergenic protein profiles of Black Tiger Shrimp (Penaeus monodon), one of the most farmed and consumed shrimp species worldwide. Protein composition was analysed in shrimp from nine different locations in the Asia–Pacific by SDS-PAGE, immunoblotting, and mass spectrometry. Ten of the twelve known shrimp allergens were detected, but with considerable differences between locations. Sarcoplasmic calcium-binding protein, myosin light chain, and tropomyosin were the most abundant allergens in all locations. Hemocyanin-specific antibodies could identify up to six different isoforms, depending on the location of origin. Similarly, tropomyosin abundance varied by up to 13 times between locations. These findings suggest that allergen abundance may be related to shrimp origin and, thus, shrimp origin might directly impact the readout of commercial crustacean allergen detection kits, most of which target tropomyosin, and this should be considered in food safety assessments. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Food Allergies)
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25 pages, 5593 KiB  
Article
Novel Allergen Discovery through Comprehensive De Novo Transcriptomic Analyses of Five Shrimp Species
by Shaymaviswanathan Karnaneedi, Roger Huerlimann, Elecia B. Johnston, Roni Nugraha, Thimo Ruethers, Aya C. Taki, Sandip D. Kamath, Nicholas M. Wade, Dean R. Jerry and Andreas L. Lopata
Int. J. Mol. Sci. 2021, 22(1), 32; https://doi.org/10.3390/ijms22010032 - 22 Dec 2020
Cited by 14 | Viewed by 4542
Abstract
Shellfish allergy affects 2% of the world’s population and persists for life in most patients. The diagnosis of shellfish allergy, in particular shrimp, is challenging due to the similarity of allergenic proteins from other invertebrates. Despite the clinical importance of immunological cross-reactivity among [...] Read more.
Shellfish allergy affects 2% of the world’s population and persists for life in most patients. The diagnosis of shellfish allergy, in particular shrimp, is challenging due to the similarity of allergenic proteins from other invertebrates. Despite the clinical importance of immunological cross-reactivity among shellfish species and between allergenic invertebrates such as dust mites, the underlying molecular basis is not well understood. Here we mine the complete transcriptome of five frequently consumed shrimp species to identify and compare allergens with all known allergen sources. The transcriptomes were assembled de novo, using Trinity, from raw RNA-Seq data of the whiteleg shrimp (Litopenaeus vannamei), black tiger shrimp (Penaeus monodon), banana shrimp (Fenneropenaeus merguiensis), king shrimp (Melicertus latisulcatus), and endeavour shrimp (Metapenaeus endeavouri). BLAST searching using the two major allergen databases, WHO/IUIS Allergen Nomenclature and AllergenOnline, successfully identified all seven known crustacean allergens. The analyses revealed up to 39 unreported allergens in the different shrimp species, including heat shock protein (HSP), alpha-tubulin, chymotrypsin, cyclophilin, beta-enolase, aldolase A, and glyceraldehyde-3-phosphate dehydrogenase (G3PD). Multiple sequence alignment (Clustal Omega) demonstrated high homology with allergens from other invertebrates including mites and cockroaches. This first transcriptomic analyses of allergens in a major food source provides a valuable resource for investigating shellfish allergens, comparing invertebrate allergens and future development of improved diagnostics for food allergy. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Food Allergies)
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10 pages, 2241 KiB  
Article
Alpha-Gal on the Protein Surface Hampers Transcytosis through the Caco-2 Monolayer
by Maja Krstić Ristivojević, Jeanette Grundström, Danijela Apostolović, Mirjana Radomirović, Vesna Jovanović, Vlad Radoi, M. B. Gea Kiewiet, Vladana Vukojević, Tanja Ćirković Veličković and Marianne van Hage
Int. J. Mol. Sci. 2020, 21(16), 5742; https://doi.org/10.3390/ijms21165742 - 11 Aug 2020
Cited by 6 | Viewed by 3143
Abstract
Transepithelial transport of proteins is an important step in the immune response to food allergens. Mammalian meat allergy is characterized by an IgE response against the carbohydrate moiety galactosyl-α-1,3-galactose (α-Gal) present on mammalian glycoproteins and glycolipids, which causes severe allergic reactions several hours [...] Read more.
Transepithelial transport of proteins is an important step in the immune response to food allergens. Mammalian meat allergy is characterized by an IgE response against the carbohydrate moiety galactosyl-α-1,3-galactose (α-Gal) present on mammalian glycoproteins and glycolipids, which causes severe allergic reactions several hours after red meat consumption. The delayed reaction may be related to the processing of α-Gal carrying proteins in the gastrointestinal tract. The aim of this study was to investigate how protein glycosylation by α-Gal affects the susceptibility to gastric digestion and transport through the Caco-2 cell monolayer. We found that α-Gal glycosylation altered protein susceptibility to gastric digestion, where large protein fragments bearing the α-Gal epitope remained for up to 2 h of digestion. Furthermore, α-Gal glycosylation of the protein hampered transcytosis of the protein through the Caco-2 monolayer. α-Gal epitope on the intact protein could be detected in the endosomal fraction obtained by differential centrifugation of Caco-2 cell lysates. Furthermore, the level of galectin-3 in Caco-2 cells was not affected by the presence of α-Gal glycosylated BSA (bovine serum albumin) (BSA-α-Gal). Taken together, our data add new knowledge and shed light on the digestion and transport of α-Gal glycosylated proteins. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Food Allergies)
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19 pages, 3881 KiB  
Article
Mechanisms of Wheat Allergenicity in Mice: Comparison of Adjuvant-Free vs. Alum-Adjuvant Models
by Yining Jin, Haoran Gao, Rick Jorgensen, Jillian Salloum, Dan Ioan Jian, Perry K.W. Ng and Venugopal Gangur
Int. J. Mol. Sci. 2020, 21(9), 3205; https://doi.org/10.3390/ijms21093205 - 01 May 2020
Cited by 7 | Viewed by 2614
Abstract
Wheat protein is considered a major type of food allergen in many countries including the USA. The mechanisms of allergenicity of wheat proteins are not well understood at present. Both adjuvant-based and adjuvant-free mouse models are reported for this food allergy. However, it [...] Read more.
Wheat protein is considered a major type of food allergen in many countries including the USA. The mechanisms of allergenicity of wheat proteins are not well understood at present. Both adjuvant-based and adjuvant-free mouse models are reported for this food allergy. However, it is unclear whether the mechanisms underlying wheat allergenicity in these two types of models are similar or different. Therefore, we compared the molecular mechanisms in a novel adjuvant-free (AF) model vs. a conventional alum-adjuvant (AA) model of wheat allergy using salt-soluble wheat protein (SSWP). In the AF model, Balb/cJ mice were sensitized with SSWP via skin exposure. In the AA model, mice were sensitized by an intraperitoneal injection of SSWP with alum. In both models, allergic reactions were elicited using an identical protocol. Robust IgE as well as mucosal mast cell protein-1 responses were elicited similarly in both models. However, an analysis of the spleen immune markers identified strikingly different molecular activation patterns in these two models. Furthermore, a number of immune markers associated with intrinsic allergenicity were also identified in both models. Since the AF model uses skin exposure without an adjuvant, the mechanisms in the AF model may more closely simulate the human wheat allergenicity mechanisms from skin exposure in occupational settings such as in the baking industry. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Food Allergies)
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19 pages, 4229 KiB  
Article
Modulating Shrimp Tropomyosin-Mediated Allergy: Hypoallergen DNA Vaccines Induce Regulatory T Cells to Reduce Hypersensitivity in Mouse Model
by Christine Y.Y. Wai, Nicki Y.H. Leung, Patrick S.C. Leung and Ka Hou Chu
Int. J. Mol. Sci. 2019, 20(18), 4656; https://doi.org/10.3390/ijms20184656 - 19 Sep 2019
Cited by 13 | Viewed by 4337
Abstract
Shellfish allergy is one of the most common food allergies, with tropomyosin as the major cross-reactive allergen. However, no allergen-specific immunotherapy is clinically available. Recently, we designed two shrimp hypoallergens MEM49 and MED171. This study aimed to examine and compare the efficacy of [...] Read more.
Shellfish allergy is one of the most common food allergies, with tropomyosin as the major cross-reactive allergen. However, no allergen-specific immunotherapy is clinically available. Recently, we designed two shrimp hypoallergens MEM49 and MED171. This study aimed to examine and compare the efficacy of the MEM49- and MED171-based DNA vaccines (pMEM49 and pMED171) in modulating shrimp allergy in a murine model of shrimp tropomyosin sensitivity. Intradermal immunization of BALB/c mice with pMEM49 or pMED171 effectively down-modulated allergic symptoms, tropomyosin-specific IgE levels, intestinal Th2 cytokines expression, and inflammatory cell infiltration. Both pMEM49 and pMED171 increased the frequency of regulatory T cells, but to a greater extent by pMED171 with upregulation of gut-homing molecules integrin-α4β7. The functionality of the pMED171-induced Treg cells was further illustrated by anti-CD25-mediated depletion of Treg cells and the adoptive transfer of CD4+CD25+Foxp3+Treg cells. Collectively, the data demonstrate that intradermal administration of pMED171 leads to the priming, activation, and migration of dermal dendritic cells which subsequently induce Treg cells, both locally and systemically, to downregulate the allergic responses to tropomyosin. This study is the first to demonstrate the potency of hypoallergen-encoding DNA vaccines as a therapeutic strategy for human shellfish allergy via the vigorous induction of functional Treg cells. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Food Allergies)
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Review

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35 pages, 2085 KiB  
Review
Egg Allergy: Diagnosis and Immunotherapy
by Dulashi Withanage Dona and Cenk Suphioglu
Int. J. Mol. Sci. 2020, 21(14), 5010; https://doi.org/10.3390/ijms21145010 - 16 Jul 2020
Cited by 41 | Viewed by 13842
Abstract
Hypersensitivity or an allergy to chicken egg proteins is a predominant symptomatic condition affecting 1 in 20 children in Australia; however, an effective form of therapy has not yet been found. This occurs as the immune system of the allergic individual overreacts when [...] Read more.
Hypersensitivity or an allergy to chicken egg proteins is a predominant symptomatic condition affecting 1 in 20 children in Australia; however, an effective form of therapy has not yet been found. This occurs as the immune system of the allergic individual overreacts when in contact with egg allergens (egg proteins), triggering a complex immune response. The subsequent instantaneous inflammatory immune response is characterized by the excessive production of immunoglobulin E (IgE) antibody against the allergen, T-cell mediators and inflammation. Current allergen-specific approaches to egg allergy diagnosis and treatment lack consistency and therefore pose safety concerns among anaphylactic patients. Immunotherapy has thus far been found to be the most efficient way to treat and relieve symptoms, this includes oral immunotherapy (OIT) and sublingual immunotherapy (SLIT). A major limitation in immunotherapy, however, is the difficulty in preparing effective and safe extracts from natural allergen sources. Advances in molecular techniques allow for the production of safe and standardized recombinant and hypoallergenic egg variants by targeting the IgE-binding epitopes responsible for clinical allergic symptoms. Site-directed mutagenesis can be performed to create such safe hypoallergens for their potential use in future methods of immunotherapy, providing a feasible standardized therapeutic approach to target egg allergies safely. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Food Allergies)
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18 pages, 1845 KiB  
Review
Overcoming Shellfish Allergy: How Far Have We Come?
by Christine Y.Y. Wai, Nicki Y.H. Leung, Ka Hou Chu, Patrick S.C. Leung, Agnes S.Y. Leung, Gary W.K. Wong and Ting Fan Leung
Int. J. Mol. Sci. 2020, 21(6), 2234; https://doi.org/10.3390/ijms21062234 - 23 Mar 2020
Cited by 42 | Viewed by 8113
Abstract
Shellfish allergy caused by undesirable immunological responses upon ingestion of crustaceans and mollusks is a common cause of food allergy, especially in the Asia-Pacific region. While the prevalence of shellfish allergy is increasing, the mainstay of clinical diagnosis for these patients includes extract-based [...] Read more.
Shellfish allergy caused by undesirable immunological responses upon ingestion of crustaceans and mollusks is a common cause of food allergy, especially in the Asia-Pacific region. While the prevalence of shellfish allergy is increasing, the mainstay of clinical diagnosis for these patients includes extract-based skin prick test and specific IgE measurement while clinical management consists of food avoidance and as-needed use of adrenaline autoinjector should they develop severe allergic reactions. Such a standard of care is unsatisfactory to both patients and healthcare practitioners. There is a pressing need to introduce more specific diagnostic methods, as well as effective and safe therapies for patients with shellfish allergy. Knowledge gained on the identifications and defining the immuno-molecular features of different shellfish allergens over the past two decades have gradually translated into the design of new diagnostic and treatment options for shellfish allergy. In this review, we will discuss the epidemiology, the molecular identification of shellfish allergens, recent progress in various diagnostic methods, as well as current development in immunotherapeutic approaches including the use of unmodified allergens, hypoallergens, immunoregulatory peptides and DNA vaccines for the prevention and treatment of shellfish allergy. The prospect of a “cure “for shellfish allergy is within reach. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Food Allergies)
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21 pages, 803 KiB  
Review
New Perspectives in Food Allergy
by Massimo De Martinis, Maria Maddalena Sirufo, Mariano Suppa and Lia Ginaldi
Int. J. Mol. Sci. 2020, 21(4), 1474; https://doi.org/10.3390/ijms21041474 - 21 Feb 2020
Cited by 128 | Viewed by 13972
Abstract
The improvement of the knowledge of the pathophysiological mechanisms underlying the tolerance and sensitization to food antigens has recently led to a radical change in the clinical approach to food allergies. Epidemiological studies show a global increase in the prevalence of food allergy [...] Read more.
The improvement of the knowledge of the pathophysiological mechanisms underlying the tolerance and sensitization to food antigens has recently led to a radical change in the clinical approach to food allergies. Epidemiological studies show a global increase in the prevalence of food allergy all over the world and manifestations of food allergy appear increasingly frequent also in elderly subjects. Environmental and nutritional changes have partly changed the epidemiology of allergic reactions to foods and new food allergic syndromes have emerged in recent years. The deepening of the study of the intestinal microbiota has highlighted important mechanisms of immunological adaptation of the mucosal immune system to food antigens, leading to a revolution in the concept of immunological tolerance. As a consequence, new prevention models and innovative therapeutic strategies aimed at a personalized approach to the patient affected by food allergy are emerging. This review focuses on these new perspectives and their practical implications in the management of food allergy, providing an updated view of this complex pathology. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Food Allergies)
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