|
1
|
Rutigliano M, Liberatore MT, Dilucia F, Quinto M, Kacmaz S, Di Luccia A, la Gatta B. Influence of Peanut Flour Enrichment and Eggs on Muffin Protein Aggregation. Foods 2025; 14:710. [PMID: 40002153 PMCID: PMC11854293 DOI: 10.3390/foods14040710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Revised: 02/11/2025] [Accepted: 02/17/2025] [Indexed: 02/27/2025] Open
Abstract
Protein-protein interactions were investigated, evaluating the influence of eggs and peanut flour on the chemical features of muffin samples. Electrophoretic, immunochemical, and chromatographic analyses were carried out to evaluate how different proteins can interact with one another, determining changes in their extractability. In this context, two extraction buffers were employed to study the rate of protein aggregate formation. Egg coagulation properties were found to affect the rate of wheat protein solubility, while the extractability of roasted peanut flour protein was less influenced and proportional to its amount in the formulation (i.e., 4% and 20%). The findings of this investigation allowed us to assume a complex form of protein organization, characterized by a "core" of wheat and egg proteins surrounded by peanut proteins, linked together through covalent reducible bonds and hydrophobic interactions. Nevertheless, the occurrence of other types of crosslinking could not be excluded.
Collapse
Affiliation(s)
- Mariacinzia Rutigliano
- Department of Sciences of Agriculture, Food, Natural Resources and Engineering (DAFNE), University of Foggia, Via Napoli, 25, 71122 Foggia, Italy; (M.R.); (M.T.L.); (F.D.); (M.Q.); (A.D.L.)
| | - Maria Teresa Liberatore
- Department of Sciences of Agriculture, Food, Natural Resources and Engineering (DAFNE), University of Foggia, Via Napoli, 25, 71122 Foggia, Italy; (M.R.); (M.T.L.); (F.D.); (M.Q.); (A.D.L.)
| | - Flavia Dilucia
- Department of Sciences of Agriculture, Food, Natural Resources and Engineering (DAFNE), University of Foggia, Via Napoli, 25, 71122 Foggia, Italy; (M.R.); (M.T.L.); (F.D.); (M.Q.); (A.D.L.)
| | - Maurizio Quinto
- Department of Sciences of Agriculture, Food, Natural Resources and Engineering (DAFNE), University of Foggia, Via Napoli, 25, 71122 Foggia, Italy; (M.R.); (M.T.L.); (F.D.); (M.Q.); (A.D.L.)
| | - Sibel Kacmaz
- Department of Food Engineering, Engineering Faculty, Giresun University, 28200 Giresun, Turkey;
| | - Aldo Di Luccia
- Department of Sciences of Agriculture, Food, Natural Resources and Engineering (DAFNE), University of Foggia, Via Napoli, 25, 71122 Foggia, Italy; (M.R.); (M.T.L.); (F.D.); (M.Q.); (A.D.L.)
| | - Barbara la Gatta
- Department of Sciences of Agriculture, Food, Natural Resources and Engineering (DAFNE), University of Foggia, Via Napoli, 25, 71122 Foggia, Italy; (M.R.); (M.T.L.); (F.D.); (M.Q.); (A.D.L.)
| |
Collapse
|
|
2
|
Rutigliano M, Liberatore MT, Dilucia F, Di Luccia A, la Gatta B. Study on the induced polymeric protein aggregation and immunoreactivity in biscuits enriched with peanut flour. Food Chem 2024; 460:140568. [PMID: 39053275 DOI: 10.1016/j.foodchem.2024.140568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 07/11/2024] [Accepted: 07/20/2024] [Indexed: 07/27/2024]
Abstract
This work deals with the study on the protein extractability of biscuits incurring different percentages of roasted peanut flour. The presence of two different flours influenced the rate of protein aggregation and protein extractability, according to the percentage of roasted peanut flour added to the formulation and assessing these features by testing the use of two buffers. Results showed that gluten network arrangement of biscuits was influenced by the flours mixture besides the baking, with possible different protein organizations. Protein extractability was affected, underlining a higher content of protein aggregates at high molecular weight especially with the addition of 20% of peanut flour, characterized by hydrophobic and reducible covalent bonds, as suggested by the higher extractability obtained with the buffer with chaotropic and reducing agents. These results suggested a possible induced supramolecular protein organization in these products, which could affect the immunoreactivity of the main allergens occurred in the formulation.
Collapse
Affiliation(s)
- Mariacinzia Rutigliano
- Department of Sciences of Agriculture, Food, Natural Resources and Engineering (DAFNE), University of Foggia, Via Napoli, 25, 71122, Foggia, Italy
| | - Maria Teresa Liberatore
- Department of Sciences of Agriculture, Food, Natural Resources and Engineering (DAFNE), University of Foggia, Via Napoli, 25, 71122, Foggia, Italy
| | - Flavia Dilucia
- Department of Sciences of Agriculture, Food, Natural Resources and Engineering (DAFNE), University of Foggia, Via Napoli, 25, 71122, Foggia, Italy
| | - Aldo Di Luccia
- Department of Sciences of Agriculture, Food, Natural Resources and Engineering (DAFNE), University of Foggia, Via Napoli, 25, 71122, Foggia, Italy
| | - Barbara la Gatta
- Department of Sciences of Agriculture, Food, Natural Resources and Engineering (DAFNE), University of Foggia, Via Napoli, 25, 71122, Foggia, Italy.
| |
Collapse
|
|
3
|
Croote D, Wong JJW, Creeks P, Aruva V, Landers JJ, Kwok M, Jama Z, Hamilton RG, Santos AF, O'Konek JJ, Ferrini R, Thomas GR, Lowman HB. Preclinical efficacy of peanut-specific IgG4 antibody therapeutic IGNX001. J Allergy Clin Immunol 2024; 154:1241-1248.e7. [PMID: 39069172 DOI: 10.1016/j.jaci.2024.07.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 06/20/2024] [Accepted: 07/16/2024] [Indexed: 07/30/2024]
Abstract
BACKGROUND Existing therapeutic strategies are challenged by long times to achieve effect and often require frequent administration. Peanut-allergic individuals would benefit from a therapeutic that provides rapid protection against accidental exposure within days of administration while carrying little risk of adverse reactions. OBJECTIVE Guided by the repertoire of human IgE mAbs from allergic individuals, we sought to develop a treatment approach leveraging the known protective effects of allergen-specific IgG4 antibodies. METHODS We applied our single-cell RNA-sequencing SEQ SIFTER platform (IgGenix, Inc, South San Francisco, Calif) to whole blood samples from peanut-allergic individuals to discover IgE mAbs. These were then class-switched by replacing the IgE constant region with IgG4 while retaining the allergen-specific variable regions. In vitro mast cell activation tests, basophil activation tests, ELISAs, and an in vivo peanut allergy mouse model were used to evaluate the specificity, affinity, and activity of these recombinant IgG4 mAbs. RESULTS We determined that human peanut-specific IgE mAbs predominantly target immunodominant epitopes on Ara h 2 and Ara h 6 and that recombinant IgG4 mAbs effectively block these epitopes. IGNX001, a mixture of 2 such high-affinity IgG4 mAbs, provided robust protection against peanut-mediated mast cell activation in vitro as well as against anaphylaxis upon intragastric peanut challenge in a peanut allergy mouse model. CONCLUSIONS We developed a peanut-specific IgG4 antibody therapeutic with convincing preclinical efficacy starting from a large repertoire of human IgE mAbs from demographically and geographically diverse individuals. These results warrant further clinical investigation of IGNX001 and underscore the opportunity for the application of this therapeutic development strategy in other food and environmental allergies.
Collapse
Affiliation(s)
| | | | | | - Venu Aruva
- IgGenix, Inc, South San Francisco, Calif
| | - Jeffrey J Landers
- Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, Mich
| | - Matthew Kwok
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom
| | - Zainab Jama
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom
| | - Robert G Hamilton
- Division of Allergy and Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md
| | - Alexandra F Santos
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom; Department of Women and Children's Health (Paediatric Allergy), School of Life Course Sciences, King's College London, London, United Kingdom; Children's Allergy Service, Evelina London, Guy's and St Thomas' Hospital, London, United Kingdom
| | - Jessica J O'Konek
- Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, Mich
| | | | | | | |
Collapse
|
|
4
|
Abu Risha M, Rick EM, Plum M, Jappe U. Legume Allergens Pea, Chickpea, Lentil, Lupine and Beyond. Curr Allergy Asthma Rep 2024; 24:527-548. [PMID: 38990406 PMCID: PMC11364600 DOI: 10.1007/s11882-024-01165-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/26/2024] [Indexed: 07/12/2024]
Abstract
PURPOSE OF THE REVIEW In the last decade, an increasing trend towards a supposedly healthier vegan diet could be observed. However, recently, more cases of allergic reactions to plants and plant-based products such as meat-substitution products, which are often prepared with legumes, were reported. Here, we provide the current knowledge on legume allergen sources and the respective single allergens. We answer the question of which legumes beside the well-known food allergen sources peanut and soybean should be considered for diagnostic and therapeutic measures. RECENT FINDINGS These "non-priority" legumes, including beans, pea, lentils, chickpea, lupine, cowpea, pigeon pea, and fenugreek, are potentially new important allergen sources, causing mild-to-severe allergic reactions. Severe reactions have been described particularly for peas and lupine. An interesting aspect is the connection between anaphylactic reactions and exercise (food-dependent exercise-induced anaphylaxis), which has only recently been highlighted for legumes such as soybean, lentils and chickpea. Most allergic reactions derive from IgE cross-reactions to homologous proteins, for example between peanut and lupine, which is of particular importance for peanut-allergic individuals ignorant to these cross-reactions. From our findings we conclude that there is a need for large-scale studies that are geographically distinctive because most studies are case reports, and geographic differences of allergic diseases towards these legumes have already been discovered for well-known "Big 9" allergen sources such as peanut and soybean. Furthermore, the review illustrates the need for a better molecular diagnostic for these emerging non-priority allergen sources to evaluate IgE cross-reactivities to known allergens and identify true allergic reactions.
Collapse
Affiliation(s)
- Marua Abu Risha
- Clinical and Molecular Allergology, Priority Research Area Chronic Lung Diseases, Research Center Borstel, Borstel, Germany
- German Center for Lung Research (DZL), Airway Research Center North (ARCN), Borstel, Germany
| | - Eva-Maria Rick
- Clinical and Molecular Allergology, Priority Research Area Chronic Lung Diseases, Research Center Borstel, Borstel, Germany
- German Center for Lung Research (DZL), Airway Research Center North (ARCN), Borstel, Germany
| | - Melanie Plum
- Clinical and Molecular Allergology, Priority Research Area Chronic Lung Diseases, Research Center Borstel, Borstel, Germany
- German Center for Lung Research (DZL), Airway Research Center North (ARCN), Borstel, Germany
| | - Uta Jappe
- Clinical and Molecular Allergology, Priority Research Area Chronic Lung Diseases, Research Center Borstel, Borstel, Germany.
- German Center for Lung Research (DZL), Airway Research Center North (ARCN), Borstel, Germany.
- Interdisciplinary Allergy Outpatient Clinic, Department of Pneumology, University of Lübeck, Lübeck, Germany.
| |
Collapse
|
|
5
|
Gonzalez-Visiedo M, Herzog RW, Munoz-Melero M, Blessinger SA, Cook-Mills JM, Daniell H, Markusic DM. Viral Vector Based Immunotherapy for Peanut Allergy. Viruses 2024; 16:1125. [PMID: 39066287 PMCID: PMC11281582 DOI: 10.3390/v16071125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 07/10/2024] [Accepted: 07/11/2024] [Indexed: 07/28/2024] Open
Abstract
Food allergy (FA) is estimated to impact up to 10% of the population and is a growing health concern. FA results from a failure in the mucosal immune system to establish or maintain immunological tolerance to innocuous dietary antigens, IgE production, and the release of histamine and other mediators upon exposure to a food allergen. Of the different FAs, peanut allergy has the highest incidence of severe allergic responses, including systemic anaphylaxis. Despite the recent FDA approval of peanut oral immunotherapy and other investigational immunotherapies, a loss of protection following cessation of therapy can occur, suggesting that these therapies do not address the underlying immune response driving FA. Our lab has shown that liver-directed gene therapy with an adeno-associated virus (AAV) vector induces transgene product-specific regulatory T cells (Tregs), eradicates pre-existing pathogenic antibodies, and protects against anaphylaxis in several models, including ovalbumin induced FA. In an epicutaneous peanut allergy mouse model, the hepatic AAV co-expression of four peanut antigens Ara h1, Ara h2, Ara h3, and Ara h6 together or the single expression of Ara h3 prevented the development of a peanut allergy. Since FA patients show a reduction in Treg numbers and/or function, we believe our approach may address this unmet need.
Collapse
Affiliation(s)
- Miguel Gonzalez-Visiedo
- Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA (M.M.-M.); (S.A.B.); (J.M.C.-M.)
| | - Roland W. Herzog
- Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA (M.M.-M.); (S.A.B.); (J.M.C.-M.)
| | - Maite Munoz-Melero
- Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA (M.M.-M.); (S.A.B.); (J.M.C.-M.)
| | - Sophia A. Blessinger
- Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA (M.M.-M.); (S.A.B.); (J.M.C.-M.)
| | - Joan M. Cook-Mills
- Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA (M.M.-M.); (S.A.B.); (J.M.C.-M.)
| | - Henry Daniell
- Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;
| | - David M. Markusic
- Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA (M.M.-M.); (S.A.B.); (J.M.C.-M.)
| |
Collapse
|
|
6
|
Ranftler C, Zehentner M, Pengl A, Röhrich A, Tschegg C, Nagl D. Purified Clinoptilolite-Tuff as an Efficient Sorbent for Food-Derived Peanut Allergens. Int J Mol Sci 2024; 25:6510. [PMID: 38928222 PMCID: PMC11203878 DOI: 10.3390/ijms25126510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 05/29/2024] [Accepted: 05/30/2024] [Indexed: 06/28/2024] Open
Abstract
The avoidance of allergen intake is crucial for persons affected by peanut allergy; however, the cross-contamination of food is common and leads to unpredictable consequences after the consumption of supposedly "safe" food. The aim of the present study was to eliminate harmful traces of peanut allergens from food using purified clinoptilolite-tuff (PCT)-a specially processed zeolite material. Analyses were performed using a peanut ELISA and a Coomassie blue (Bradford) assay. Mimicking conditions of the human gastrointestinal tract demonstrated a higher efficacy of PCT in the intestine (pH 6.8) than in the stomach (pH 1.5). Adsorption rates were fast (<2 min) and indicated high capacities (23 µg and 40 µg per 1 mg of PCT at pH 1.5 and pH 6.8, respectively). Allergenically relevant peanut protein concentrations were sorbed in artificial fluids (32 µg/mL by 4 mg/mL of PCT at pH 1.5 and 80.8 µg/mL by 0.25 mg/mL of PCT at pH 6.8) when imitating a daily dose of 2 g of PCT in an average stomach volume of 500 mL. Experiments focusing on the bioavailability of peanut protein attached to PCT revealed sustained sorption at pH 1.5 and only minor desorption at pH 6.8. Accompanied by gluten, peanut proteins showed competing binding characteristics with PCT. This study therefore demonstrates the potential of PCT in binding relevant quantities of peanut allergens during the digestion of peanut-contaminated food.
Collapse
Affiliation(s)
| | | | | | | | | | - Dietmar Nagl
- GLOCK Health, Science and Research GmbH, Hausfeldstrasse 17, 2232 Deutsch-Wagram, Austria; (C.R.); (M.Z.); (A.P.); (A.R.); (C.T.)
| |
Collapse
|
|
7
|
Yang P, Wang X, Wang H, Hu Y, Wen P, Tu Z. The decrease of Ara h 2 allergenicity by glycation is determined by reducing sugar chain length and isomers. Food Chem 2024; 432:137289. [PMID: 37659330 DOI: 10.1016/j.foodchem.2023.137289] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 08/14/2023] [Accepted: 08/24/2023] [Indexed: 09/04/2023]
Abstract
The mechanism of the effect of reducing sugar chain length and isomers on the allergenicity of Ara h 2 after glycation was investigated. Ara h 2 was more prone to glycation with ribose which had a short chain length. The glycation sites of Ara h 2 after glycation with galactose were higher than the glycation sites in galactose's isomers-Ara h 2 conjugates, which might be affected by the configuration differences at position C-4 and the small steric effects in terminal groups -CHO of galactose. Ara h 2-ribose conjugate had the lowest allergenicity, and glycation with galactose was more capable of reducing Ara h 2 allergenicity than its isomers. The results indicated that glycation with ribose caused conformational epitope destruction and linear epitope masking of Ara h 2 greatly. Furthermore, since the small steric effects of -CHO, galactose was more capable of reducing Ara h 2 allergenicity than fructose. This study will provide a theoretical basis for selecting appropriate reducing sugars and preparing hypoallergenic products containing peanuts.
Collapse
Affiliation(s)
- Ping Yang
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, Jiangxi 330047, China
| | - Xumei Wang
- College of Health, Jiangxi Normal University, Nanchang, Jiangxi 330022, China; National R&D Center of Freshwater Fish Processing and Engineering Research Center of Freshwater Fish High-value Utilization of Jiangxi Province, Jiangxi Normal University, Nanchang, Jiangxi 330022, China
| | - Hui Wang
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, Jiangxi 330047, China.
| | - Yueming Hu
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, Jiangxi 330047, China
| | - Pingwei Wen
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, Jiangxi 330047, China
| | - Zongcai Tu
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, Jiangxi 330047, China; National R&D Center of Freshwater Fish Processing and Engineering Research Center of Freshwater Fish High-value Utilization of Jiangxi Province, Jiangxi Normal University, Nanchang, Jiangxi 330022, China
| |
Collapse
|
|
8
|
Croote D, Wong JJW, Pecalvel C, Leveque E, Casanovas N, Kamphuis JBJ, Creeks P, Romero J, Sohail S, Bedinger D, Nadeau KC, Chinthrajah RS, Reber LL, Lowman HB. Widespread monoclonal IgE antibody convergence to an immunodominant, proanaphylactic Ara h 2 epitope in peanut allergy. J Allergy Clin Immunol 2024; 153:182-192.e7. [PMID: 37748654 PMCID: PMC10766438 DOI: 10.1016/j.jaci.2023.08.035] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 07/25/2023] [Accepted: 08/31/2023] [Indexed: 09/27/2023]
Abstract
BACKGROUND Despite their central role in peanut allergy, human monoclonal IgE antibodies have eluded characterization. OBJECTIVE We sought to define the sequences, affinities, clonality, and functional properties of human monoclonal IgE antibodies in peanut allergy. METHODS We applied our single-cell RNA sequencing-based SEQ SIFTER discovery platform to samples from allergic individuals who varied by age, sex, ethnicity, and geographic location in order to understand commonalities in the human IgE response to peanut allergens. Select antibodies were then recombinantly expressed and characterized for their allergen and epitope specificity, affinity, and functional properties. RESULTS We found striking convergent evolution of IgE monoclonal antibodies (mAbs) from several clonal families comprising both memory B cells and plasmablasts. These antibodies bound with subnanomolar affinity to the immunodominant peanut allergen Ara h 2, specifically a linear, repetitive motif. Further characterization of these mAbs revealed their ability to single-handedly cause affinity-dependent degranulation of human mast cells and systemic anaphylaxis on peanut allergen challenge in humanized mice. Finally, we demonstrated that these mAbs, reengineered as IgGs, inhibit significant, but variable, amounts of Ara h 2- and peanut-mediated degranulation of mast cells sensitized with allergic plasma. CONCLUSIONS Convergent evolution of IgE mAbs in peanut allergy is a common phenomenon that can reveal immunodominant epitopes on major allergenic proteins. Understanding the functional properties of these molecules is key to developing therapeutics, such as competitive IgG inhibitors, that are able to stoichiometrically outcompete endogenous IgE for allergen and thereby prevent allergic cascade in cases of accidental allergen exposure.
Collapse
Affiliation(s)
| | | | - Cyprien Pecalvel
- Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), UMR 1291, University of Toulouse, INSERM, CNRS, Toulouse, France
| | - Edouard Leveque
- Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), UMR 1291, University of Toulouse, INSERM, CNRS, Toulouse, France
| | - Natacha Casanovas
- Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), UMR 1291, University of Toulouse, INSERM, CNRS, Toulouse, France
| | - Jasper B J Kamphuis
- Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), UMR 1291, University of Toulouse, INSERM, CNRS, Toulouse, France
| | | | | | | | | | - Kari C Nadeau
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif; Department of Medicine, Stanford University School of Medicine, Stanford, Calif
| | - Rebecca S Chinthrajah
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif; Department of Medicine, Stanford University School of Medicine, Stanford, Calif
| | - Laurent L Reber
- Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), UMR 1291, University of Toulouse, INSERM, CNRS, Toulouse, France
| | | |
Collapse
|
|
9
|
Castenmiller C, Nagy NA, Kroon PZ, Auger L, Desgagnés R, Martel C, Mirande L, Morel B, Roberge J, Stordeur V, Tropper G, Vézina LP, van Ree R, Gomord V, de Jong EC. A novel peanut allergy immunotherapy: Plant-based enveloped Ara h 2 Bioparticles activate dendritic cells and polarize T cell responses to Th1. World Allergy Organ J 2023; 16:100839. [PMID: 38020282 PMCID: PMC10679945 DOI: 10.1016/j.waojou.2023.100839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 09/19/2023] [Accepted: 10/17/2023] [Indexed: 12/01/2023] Open
Abstract
Introduction As the only market-authorized allergen immunotherapy (AIT) for peanut allergy is accompanied by a high risk of side effects and mainly induces robust desensitization without sustained efficacy, novel treatment options are required. Peanut-specific plant-derived eBioparticles (eBPs) surface expressing Ara h 2 at high density have been shown to be very hypoallergenic. Here, we assessed the dendritic cell (DC)-activating and T cell polarization capacity of these peanut-specific eBPs. Methods Route and kinetics of eBP uptake were studied by (imaging) flow cytometry using monocyte-derived DCs incubated with fluorescently-labelled Ara h 2 eBPs or natural Ara h 2 (nAra h 2) in the presence or absence of inhibitors that block pathways involved in macropinocytosis, phagocytosis, and/or receptor-mediated uptake. DC activation was monitored by flow cytometry (maturation marker expression) and ELISA (cytokine production). T cell polarization was assessed by co-culturing DCs exposed to Ara h 2 eBPs or nAra h 2 with naïve CD4+ T cells, followed by flow cytometry assessment of intracellular IFNγ+ (Th1) and IL-13+ (Th2), and CD25+CD127-Foxp3+ regulatory T cells (Tregs). The suppressive activity of Tregs was tested using a suppressor assay. Results Ara h 2 eBPs were taken up by DCs through actin-dependent pathways. They activated DCs demonstrated by an induced expression of CD83 and CD86, and production of TNFα, IL-6, and IL-10. eBP-treated DCs polarized naïve CD4+ T cells towards Th1 cells, while reducing Th2 cell development. Furthermore, eBP-treated DCs induced reduced the frequency of Foxp3+ Tregs but did not significantly affect T cell IL-10 production or T cells with suppressive capacity. In contrast, DC activation and Th1 cell polarization were not observed for nAra h 2. Conclusion Ara h 2 eBPs activate DCs that subsequently promote Th1 cell polarization and reduce Th2 cell polarization. These characteristics mark Ara h 2 eBPs as a promising novel candidate for peanut AIT.
Collapse
Affiliation(s)
- Charlotte Castenmiller
- Department of Experimental Immunology, Amsterdam University Medical Centers, Amsterdam Institute for Infection & Immunity, University of Amsterdam, Amsterdam, the Netherlands
| | - Noémi Anna Nagy
- Department of Experimental Immunology, Amsterdam University Medical Centers, Amsterdam Institute for Infection & Immunity, University of Amsterdam, Amsterdam, the Netherlands
| | - Pascal Zion Kroon
- Department of Experimental Immunology, Amsterdam University Medical Centers, Amsterdam Institute for Infection & Immunity, University of Amsterdam, Amsterdam, the Netherlands
| | | | | | | | | | | | | | | | | | | | - Ronald van Ree
- Department of Experimental Immunology, Amsterdam University Medical Centers, Amsterdam Institute for Infection & Immunity, University of Amsterdam, Amsterdam, the Netherlands
- Department of Otorhinolaryngology, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | | | - Esther Christina de Jong
- Department of Experimental Immunology, Amsterdam University Medical Centers, Amsterdam Institute for Infection & Immunity, University of Amsterdam, Amsterdam, the Netherlands
| |
Collapse
|
|
10
|
Yang X, Bai H, Yin L, Wang J, Xue W, Jia X. Evaluation of allergenic protein profiles in three Chinese high-oleic acid peanut cultivars using NanoLC-Orbitrap mass spectrometry. FOOD SCIENCE AND HUMAN WELLNESS 2023. [DOI: 10.1016/j.fshw.2022.09.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
|
|
11
|
Dramburg S, Hilger C, Santos AF, de Las Vecillas L, Aalberse RC, Acevedo N, Aglas L, Altmann F, Arruda KL, Asero R, Ballmer-Weber B, Barber D, Beyer K, Biedermann T, Bilo MB, Blank S, Bosshard PP, Breiteneder H, Brough HA, Bublin M, Campbell D, Caraballo L, Caubet JC, Celi G, Chapman MD, Chruszcz M, Custovic A, Czolk R, Davies J, Douladiris N, Eberlein B, Ebisawa M, Ehlers A, Eigenmann P, Gadermaier G, Giovannini M, Gomez F, Grohman R, Guillet C, Hafner C, Hamilton RG, Hauser M, Hawranek T, Hoffmann HJ, Holzhauser T, Iizuka T, Jacquet A, Jakob T, Janssen-Weets B, Jappe U, Jutel M, Kalic T, Kamath S, Kespohl S, Kleine-Tebbe J, Knol E, Knulst A, Konradsen JR, Korošec P, Kuehn A, Lack G, Le TM, Lopata A, Luengo O, Mäkelä M, Marra AM, Mills C, Morisset M, Muraro A, Nowak-Wegrzyn A, Nugraha R, Ollert M, Palosuo K, Pastorello EA, Patil SU, Platts-Mills T, Pomés A, Poncet P, Potapova E, Poulsen LK, Radauer C, Radulovic S, Raulf M, Rougé P, Sastre J, Sato S, Scala E, Schmid JM, Schmid-Grendelmeier P, Schrama D, Sénéchal H, Traidl-Hoffmann C, Valverde-Monge M, van Hage M, van Ree R, Verhoeckx K, Vieths S, Wickman M, Zakzuk J, Matricardi PM, et alDramburg S, Hilger C, Santos AF, de Las Vecillas L, Aalberse RC, Acevedo N, Aglas L, Altmann F, Arruda KL, Asero R, Ballmer-Weber B, Barber D, Beyer K, Biedermann T, Bilo MB, Blank S, Bosshard PP, Breiteneder H, Brough HA, Bublin M, Campbell D, Caraballo L, Caubet JC, Celi G, Chapman MD, Chruszcz M, Custovic A, Czolk R, Davies J, Douladiris N, Eberlein B, Ebisawa M, Ehlers A, Eigenmann P, Gadermaier G, Giovannini M, Gomez F, Grohman R, Guillet C, Hafner C, Hamilton RG, Hauser M, Hawranek T, Hoffmann HJ, Holzhauser T, Iizuka T, Jacquet A, Jakob T, Janssen-Weets B, Jappe U, Jutel M, Kalic T, Kamath S, Kespohl S, Kleine-Tebbe J, Knol E, Knulst A, Konradsen JR, Korošec P, Kuehn A, Lack G, Le TM, Lopata A, Luengo O, Mäkelä M, Marra AM, Mills C, Morisset M, Muraro A, Nowak-Wegrzyn A, Nugraha R, Ollert M, Palosuo K, Pastorello EA, Patil SU, Platts-Mills T, Pomés A, Poncet P, Potapova E, Poulsen LK, Radauer C, Radulovic S, Raulf M, Rougé P, Sastre J, Sato S, Scala E, Schmid JM, Schmid-Grendelmeier P, Schrama D, Sénéchal H, Traidl-Hoffmann C, Valverde-Monge M, van Hage M, van Ree R, Verhoeckx K, Vieths S, Wickman M, Zakzuk J, Matricardi PM, Hoffmann-Sommergruber K. EAACI Molecular Allergology User's Guide 2.0. Pediatr Allergy Immunol 2023; 34 Suppl 28:e13854. [PMID: 37186333 DOI: 10.1111/pai.13854] [Show More Authors] [Citation(s) in RCA: 102] [Impact Index Per Article: 51.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 09/05/2022] [Indexed: 05/17/2023]
Abstract
Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE-mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE-mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well-defined, highly pure molecules for component-resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the "EAACI Molecular Allergology User's Guide" (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state-of-the-art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure.
Collapse
Affiliation(s)
- Stephanie Dramburg
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Christiane Hilger
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
| | - Alexandra F Santos
- Department of Women and Children's Health (Pediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom
- Children's Allergy Service, Evelina London, Guy's and St Thomas' Hospital, London, United Kingdom
| | | | - Rob C Aalberse
- Sanquin Research, Dept Immunopathology, University of Amsterdam, Amsterdam, The Netherlands
- Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - Nathalie Acevedo
- Institute for Immunological Research, University of Cartagena, Cartagena de Indias, Colombia, Colombia
| | - Lorenz Aglas
- Department of Biosciences and Medical Biology, Paris Lodron University Salzburg, Salzburg, Austria
| | - Friedrich Altmann
- Department of Chemistry, University of Natural Resources and Life Sciences, Vienna, Austria
| | - Karla L Arruda
- Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Sao Paulo, Brasil, Brazil
| | - Riccardo Asero
- Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano, Italy
| | - Barbara Ballmer-Weber
- Klinik für Dermatologie und Allergologie, Kantonsspital St. Gallen, St. Gallen, Switzerland
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
| | - Domingo Barber
- Institute of Applied Molecular Medicine Nemesio Diez (IMMAND), Department of Basic Medical Sciences, Facultad de Medicina, Universidad San Pablo CEU, CEU Universities, Madrid, Spain
- RETIC ARADyAL and RICORS Enfermedades Inflamatorias (REI), Madrid, Spain
| | - Kirsten Beyer
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Tilo Biedermann
- Department of Dermatology and Allergy Biederstein, School of Medicine, Technical University Munich, Munich, Germany
| | - Maria Beatrice Bilo
- Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy
- Allergy Unit Department of Internal Medicine, University Hospital Ospedali Riuniti di Ancona, Torrette, Italy
| | - Simon Blank
- Center of Allergy and Environment (ZAUM), Technical University of Munich, School of Medicine and Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany
| | - Philipp P Bosshard
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
| | - Heimo Breiteneder
- Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
| | - Helen A Brough
- Department of Women and Children's Health (Pediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom
- Children's Allergy Service, Evelina London, Guy's and St Thomas' Hospital, London, United Kingdom
| | - Merima Bublin
- Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
| | - Dianne Campbell
- Department of Allergy and Immunology, Children's Hospital at Westmead, Sydney Children's Hospitals Network, Sydney, New South Wales, Australia
- Child and Adolescent Health, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
| | - Luis Caraballo
- Institute for Immunological Research, University of Cartagena, Cartagena de Indias, Colombia, Colombia
| | - Jean Christoph Caubet
- Pediatric Allergy Unit, Department of Child and Adolescent, University Hospitals of Geneva, Geneva, Switzerland
| | - Giorgio Celi
- Centro DH Allergologia e Immunologia Clinica ASST- MANTOVA (MN), Mantova, Italy
| | | | - Maksymilian Chruszcz
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, USA
| | - Adnan Custovic
- National Heart and Lung Institute, Imperial College London, London, UK
| | - Rebecca Czolk
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
- Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Janet Davies
- Queensland University of Technology, Centre for Immunology and Infection Control, School of Biomedical Sciences, Herston, Queensland, Australia
- Metro North Hospital and Health Service, Emergency Operations Centre, Herston, Queensland, Australia
| | - Nikolaos Douladiris
- Allergy Department, 2nd Paediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece
| | - Bernadette Eberlein
- Department of Dermatology and Allergy Biederstein, School of Medicine, Technical University Munich, Munich, Germany
| | - Motohiro Ebisawa
- Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan
| | - Anna Ehlers
- Chemical Biology and Drug Discovery, Utrecht University, Utrecht, The Netherlands
- Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
- Department of Immunology and Dermatology/ Allergology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Philippe Eigenmann
- Pediatric Allergy Unit, Department of Child and Adolescent, University Hospitals of Geneva, Geneva, Switzerland
| | - Gabriele Gadermaier
- Department of Biosciences and Medical Biology, Paris Lodron University Salzburg, Salzburg, Austria
| | - Mattia Giovannini
- Allergy Unit, Department of Pediatrics, Meyer Children's University Hospital, Florence, Italy
| | - Francisca Gomez
- Allergy Unit IBIMA-Hospital Regional Universitario de Malaga, Malaga, Spain
- Spanish Network for Allergy research RETIC ARADyAL, Malaga, Spain
| | - Rebecca Grohman
- NYU Langone Health, Department of Internal Medicine, New York, New York, USA
| | - Carole Guillet
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | - Christine Hafner
- Department of Dermatology, University Hospital St. Poelten, Karl Landsteiner University of Health Sciences, St. Poelten, Austria
| | - Robert G Hamilton
- Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Michael Hauser
- Department of Biosciences and Medical Biology, Paris Lodron University Salzburg, Salzburg, Austria
| | - Thomas Hawranek
- Department of Dermatology and Allergology, Paracelsus Private Medical University, Salzburg, Austria
| | - Hans Jürgen Hoffmann
- Institute for Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark
- Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark
| | | | - Tomona Iizuka
- Laboratory of Protein Science, Graduate School of Life Science, Hokkaido University, Sapporo, Japan
| | - Alain Jacquet
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Thilo Jakob
- Department of Dermatology and Allergology, University Medical Center, Justus Liebig University Gießen, Gießen, Germany
| | - Bente Janssen-Weets
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
- Odense Research Center for Anaphylaxis, University of Southern Denmark, Odense, Denmark
| | - Uta Jappe
- Division of Clinical and Molecular Allergology, Priority Research Area Asthma and Allergy, Research Center Borstel, Borstel, Germany
- Leibniz Lung Center, Airway Research Center North (ARCN), Member of the German Center for Lung Research, Germany
- Interdisciplinary Allergy Outpatient Clinic, Dept. of Pneumology, University of Lübeck, Lübeck, Germany
| | - Marek Jutel
- Department of Clinical Immunology, Wroclaw Medical University, Wroclaw, Poland
| | - Tanja Kalic
- Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
- Department of Dermatology, University Hospital St. Poelten, Karl Landsteiner University of Health Sciences, St. Poelten, Austria
| | - Sandip Kamath
- Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia
- Molecular Allergy Research Laboratory, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia
| | - Sabine Kespohl
- Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr- Universität Bochum, Bochum, Germany
| | - Jörg Kleine-Tebbe
- Allergy & Asthma Center Westend, Outpatient Clinic and Clinical Research Center, Berlin, Germany
| | - Edward Knol
- Department of Immunology and Dermatology/ Allergology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - André Knulst
- Department of Immunology and Dermatology/ Allergology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Jon R Konradsen
- Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
- Pediatric Allergy and Pulmonology Unit at Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden
| | - Peter Korošec
- University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia
- Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
| | - Annette Kuehn
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
| | - Gideon Lack
- Department of Women and Children's Health (Pediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom
- Children's Allergy Service, Evelina London, Guy's and St Thomas' Hospital, London, United Kingdom
| | - Thuy-My Le
- Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
- Department of Immunology and Dermatology/ Allergology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Andreas Lopata
- Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia
- Molecular Allergy Research Laboratory, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia
| | - Olga Luengo
- RETIC ARADyAL and RICORS Enfermedades Inflamatorias (REI), Madrid, Spain
- Allergy Section, Internal Medicine Department, Vall d'Hebron University Hospital, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Mika Mäkelä
- Division of Allergy, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
- Pediatric Department, Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland
| | | | - Clare Mills
- Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Manchester Institute of Biotechnology, The University of Manchester, Manchester, UK
| | | | - Antonella Muraro
- Food Allergy Referral Centre, Department of Woman and Child Health, Padua University Hospital, Padua, Italy
| | - Anna Nowak-Wegrzyn
- Division of Pediatric Allergy and Immunology, NYU Grossman School of Medicine, Hassenfeld Children's Hospital, New York, New York, USA
- Department of Pediatrics, Gastroenterology and Nutrition, Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland
| | - Roni Nugraha
- Molecular Allergy Research Laboratory, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia
- Department of Aquatic Product Technology, Faculty of Fisheries and Marine Science, IPB University, Bogor, Indonesia
| | - Markus Ollert
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
- Odense Research Center for Anaphylaxis, University of Southern Denmark, Odense, Denmark
| | - Kati Palosuo
- Department of Allergology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | | | - Sarita Ulhas Patil
- Division of Rheumatology, Allergy and Immunology, Departments of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Division of Allergy and Immunology, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Thomas Platts-Mills
- Division of Allergy and Clinical Immunology, University of Virginia, Charlottesville, Virginia, USA
| | | | - Pascal Poncet
- Institut Pasteur, Immunology Department, Paris, France
- Allergy & Environment Research Team Armand Trousseau Children Hospital, APHP, Paris, France
| | - Ekaterina Potapova
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Lars K Poulsen
- Allergy Clinic, Department of Dermatology and Allergy, Copenhagen University Hospital-Herlev and Gentofte, Copenhagen, Denmark
| | - Christian Radauer
- Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
| | - Suzana Radulovic
- Department of Women and Children's Health (Pediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom
- Children's Allergy Service, Evelina London, Guy's and St Thomas' Hospital, London, United Kingdom
| | - Monika Raulf
- Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr- Universität Bochum, Bochum, Germany
| | - Pierre Rougé
- UMR 152 PharmaDev, IRD, Université Paul Sabatier, Faculté de Pharmacie, Toulouse, France
| | - Joaquin Sastre
- Allergy Service, Fundación Jiménez Díaz; CIBER de Enfermedades Respiratorias (CIBERES); Faculty of Medicine, Universidad Autonoma de Madrid, Madrid, Spain
| | - Sakura Sato
- Allergy Department, 2nd Paediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece
| | - Enrico Scala
- Clinical and Laboratory Molecular Allergy Unit - IDI- IRCCS, Fondazione L M Monti Rome, Rome, Italy
| | - Johannes M Schmid
- Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark
| | - Peter Schmid-Grendelmeier
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
- Christine Kühne Center for Allergy Research and Education CK-CARE, Davos, Switzerland
| | - Denise Schrama
- Centre of Marine Sciences (CCMAR), Universidade do Algarve, Faro, Portugal
| | - Hélène Sénéchal
- Allergy & Environment Research Team Armand Trousseau Children Hospital, APHP, Paris, France
| | - Claudia Traidl-Hoffmann
- Christine Kühne Center for Allergy Research and Education CK-CARE, Davos, Switzerland
- Department of Environmental Medicine, Faculty of Medicine, University of Augsburg, Augsburg, Germany
| | - Marcela Valverde-Monge
- Allergy Service, Fundación Jiménez Díaz; CIBER de Enfermedades Respiratorias (CIBERES); Faculty of Medicine, Universidad Autonoma de Madrid, Madrid, Spain
| | - Marianne van Hage
- Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden
- Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Ronald van Ree
- Department of Experimental Immunology and Department of Otorhinolaryngology, Amsterdam University Medical Centers, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Kitty Verhoeckx
- Department of Immunology and Dermatology/ Allergology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Stefan Vieths
- Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany
| | - Magnus Wickman
- Department of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Josefina Zakzuk
- Institute for Immunological Research, University of Cartagena, Cartagena de Indias, Colombia, Colombia
| | - Paolo M Matricardi
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | | |
Collapse
|
|
12
|
Ji C, Huang Y, Yeung LH, Hemmings O, Jama Z, Kwok M, Lack G, Santos AF. Ara h 2-Specific IgE Presence Rather Than Its Function Is the Best Predictor of Mast Cell Activation in Children. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2022; 11:1154-1161.e3. [PMID: 36581066 DOI: 10.1016/j.jaip.2022.12.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 12/07/2022] [Accepted: 12/09/2022] [Indexed: 12/28/2022]
Abstract
BACKGROUND Ara h 2-specific IgE (Arah2-sIgE) is an excellent serologic marker for peanut allergy. However, not all subjects with detectable Arah2-sIgE react clinically. OBJECTIVE To assess the importance of functional characteristics of Arah2-sIgE for Ara h 2-induced mast cell activation. METHODS We studied a cohort of children assessed for peanut allergy. We determined Arah2-sIgE levels, Ara h 2/total IgE ratios and IgE avidity for Ara h 2 using ImmunoCAP (Thermo Fisher) and mast cell activation to Ara h 2 using flow cytometry. RESULTS Samples from 61 of 100 children (46 peanut-allergic [PA] and 15 peanut-sensitized tolerant) who had Arah2-sIgE levels 0.10 kU/L or greater were studied. Arah2-sIgE and Ara h 6-specific IgE levels, Ara h 2/total IgE ratios, and the diversity of IgE for Ara h 2 epitopes were higher in PA compared with peanut-sensitized tolerant samples. The levels of IgE to peanut, Ara h 1, and Ara h 3 were not significantly different between groups. Results from the mast cell activation test to Ara h 2 strongly correlated with Arah2-sIgE levels (r = 0.722; P < .001) and Ara h 2/total IgE ratios (r = 0.697; P < .001) and moderately with Arah2-sIgE diversity (r = 0.540; P < .001). On a linear regression model, Arah2-sIgE levels (standardized β-coefficient = 0.396; P = .008) and Ara h 2/total IgE ratios (standardized β-coefficient = 0.0.669; P = .002) were the main determinants of mast cell response to Ara h 2. CONCLUSIONS Most children sensitized to Ara h 2 are PA. Ara h 2-specific IgE titers and specific activity are the major determinants of mast cell response to Ara h 2.
Collapse
Affiliation(s)
- Chen Ji
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom
| | - Yue Huang
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom
| | - Long Him Yeung
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom
| | - Oliver Hemmings
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom; Department of Women and Children's Health (Pediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom; Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom
| | - Zainab Jama
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom; Department of Women and Children's Health (Pediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom; Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom
| | - Matthew Kwok
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom; Department of Women and Children's Health (Pediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom; Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom
| | - Gideon Lack
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom; Department of Women and Children's Health (Pediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom; Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom; Children's Allergy Service, Evelina London Children's Hospital, Guy's and St Thomas' Hospital, London, United Kingdom
| | - Alexandra F Santos
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom; Department of Women and Children's Health (Pediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom; Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom; Children's Allergy Service, Evelina London Children's Hospital, Guy's and St Thomas' Hospital, London, United Kingdom.
| |
Collapse
|
|
13
|
Drønen EK, Namork E, Dirven H, Nygaard UC. Suspected gut barrier disruptors and development of food allergy: Adjuvant effects and early immune responses. FRONTIERS IN ALLERGY 2022; 3:1029125. [PMID: 36483186 PMCID: PMC9723362 DOI: 10.3389/falgy.2022.1029125] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 11/03/2022] [Indexed: 08/22/2023] Open
Abstract
Food allergy is an increasing public health challenge worldwide. It has recently been hypothesized that the increase in exposure to intestinal epithelial barrier-damaging biological and chemical agents contribute to this development. In animal models, exposure to adjuvants with a food allergen has been shown to promote sensitization and development of food allergy, and barrier disrupting capacities have been suggested to be one mechanism of adjuvant action. Here, we investigated how gut barrier disrupting compounds affected food allergy development in a mouse model of peanut allergy. Sensitization and clinical peanut allergy in C3H/HEOuJ mice were assessed after repeated oral exposure to peanut extract together with cholera toxin (CT; positive control), the mycotoxin deoxynivalenol (DON), house dust mite (HDM) or the pesticide glyphosate (GLY). In addition, we investigated early effects 4 to 48 h after a single exposure to the compounds by assessing markers of intestinal barrier permeability, alarmin production, intestinal epithelial responses, and local immune responses. CT and DON exerted adjuvant effects on peanut allergy development assessed as clinical anaphylaxis in mice. Early markers were affected only by DON, observed as increased IL-33 (interleukin 33) and thymic stromal lymphopoietin (TSLP) alarmin production in intestines and IL-33 receptor ST2 in serum. DON also induced an inflammatory immune response in lymph node cells stimulated with lipopolysaccharide (LPS). HDM and GLY did not clearly promote clinical food allergy and affected few of the early markers at the doses tested. In conclusion, oral exposure to CT and DON promoted development of clinical anaphylaxis in the peanut allergy mouse model. DON, but not CT, affected the early markers measured in this study, indicating that DON and CT have different modes of action at the early stages of peanut sensitization.
Collapse
Affiliation(s)
- Elena Klåpbakken Drønen
- Department for Chemical Toxicology, Division for Climate and Health, Norwegian Institute of Public Health, Oslo, Norway
| | - Ellen Namork
- Department for Chemical Toxicology, Division for Climate and Health, Norwegian Institute of Public Health, Oslo, Norway
| | - Hubert Dirven
- Department for Chemical Toxicology, Division for Climate and Health, Norwegian Institute of Public Health, Oslo, Norway
| | - Unni Cecilie Nygaard
- Department for Chemical Toxicology, Division for Climate and Health, Norwegian Institute of Public Health, Oslo, Norway
- Section for Immunology, Division for Infection Control, Norwegian Institute of Public Health, Oslo, Norway
| |
Collapse
|
|
14
|
Hazebrouck S, Patil SU, Guillon B, Lahood N, Dreskin SC, Adel-Patient K, Bernard H. Immunodominant conformational and linear IgE epitopes lie in a single segment of Ara h 2. J Allergy Clin Immunol 2022; 150:131-139. [PMID: 35150723 PMCID: PMC10440805 DOI: 10.1016/j.jaci.2021.12.796] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Revised: 12/16/2021] [Accepted: 12/27/2021] [Indexed: 11/21/2022]
Abstract
BACKGROUND Contribution of conformational epitopes to the IgE reactivity of peanut allergens Ara h 2 and Ara h 6 is at least as important as that of the linear epitopes. However, little is known about these conformational IgE-binding epitopes. OBJECTIVE We investigated the distribution of conformational epitopes on chimeric 2S-albumins. METHODS Recombinant chimeras were generated by exchanging structural segments between Ara h 2 and Ara h 6. Well-refolded chimeras, as verified by circular dichroism analysis, were then used to determine the epitope specificity of mAbs by performing competitive inhibition of IgG binding. Furthermore, we delineated the contribution of each segment to the overall IgE reactivity of both 2S-albumins by measuring the chimeras' IgE-binding capacity with sera from 21 patients allergic to peanut. We finally assessed chimeras' capacity to trigger mast cell degranulation. RESULTS Configuration of the conformational epitopes was preserved in the chimeras. Mouse IgG mAbs, raised against natural Ara h 6, and polyclonal human IgE antibodies recognized different conformational epitopes distributed all along Ara h 6. In contrast, we identified human IgG mAbs specific to different Ara h 2 linear or conformational epitopes located in all segments except the C-terminal one. The major conformational IgE-binding epitope of Ara h 2 was located in a segment located between residues 33 and 81 that also contains the major linear hydroxyproline-containing epitope. Accordingly, this segment is critical for the capacity of Ara h 2 to induce mast cell degranulation. CONCLUSIONS Chimeric 2S-albumins provide new insights on the conformational IgE-binding epitopes of Ara h 2 and Ara h 6. Proximity of the immunodominant linear and conformational IgE-binding epitopes probably contributes to the high allergenic potency of Ara h 2.
Collapse
Affiliation(s)
- Stéphane Hazebrouck
- Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SPI, Gif-sur-Yvette, France.
| | - Sarita U Patil
- Department of Medicine, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, the Food Allergy Center, Massachusetts General Hospital for Children, and Harvard Medical School, Boston, Mass
| | - Blanche Guillon
- Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SPI, Gif-sur-Yvette, France
| | - Nicole Lahood
- Department of Medicine, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, the Food Allergy Center, Massachusetts General Hospital for Children, and Harvard Medical School, Boston, Mass
| | - Stephen C Dreskin
- Division of Allergy and Clinical Immunology, Department of Medicine, University of Colorado-Denver, Aurora, Colo
| | - Karine Adel-Patient
- Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SPI, Gif-sur-Yvette, France
| | - Hervé Bernard
- Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SPI, Gif-sur-Yvette, France
| |
Collapse
|
|
15
|
Abstract
This review provides a global overview on Rosaceae allergy and details the particularities of each fruit allergy induced by ten Rosaceae species: almond/peach/cherry/apricot/plum (Amygdaleae), apple/pear (Maleae), and raspberry/blackberry/strawberry (Rosoideae). Data on clinical symptoms, prevalence, diagnosis, and immunotherapies for the treatment of Rosaceae allergy are herein stated. Allergen molecular characterization, cross-reactivity/co-sensitization phenomena, the impact of food processing and digestibility, and the methods currently available for the Rosaceae detection/quantification in foods are also described. Rosaceae allergy has a major impact in context to pollen-food allergy syndrome (PFAS) and lipid transfer protein (LTP) allergies, being greatly influenced by geography, environment, and presence of cofactors. Peach, apple, and almond allergies are probably the ones most affecting the quality of life of the allergic-patients, although allergies to other Rosaceae fruits cannot be overlooked. From patients' perspective, self-allergy management and an efficient avoidance of multiple fruits are often difficult to achieve, which might raise the risk for cross-reactivity and co-sensitization phenomena and increase the severity of the induced allergic responses with time. At this point, the absence of effective allergy diagnosis (lack of specific molecular markers) and studies advancing potential immunotherapies are some gaps that certainly will prompt the progress on novel strategies to manage Rosaceae food allergies.
Collapse
Affiliation(s)
- Joana Costa
- REQUIMTE-LAQV, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
| | - Isabel Mafra
- REQUIMTE-LAQV, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
| |
Collapse
|
|
16
|
Hazebrouck S, Canon N, Dreskin SC. The Effector Function of Allergens. FRONTIERS IN ALLERGY 2022; 3:818732. [PMID: 35386644 PMCID: PMC8974742 DOI: 10.3389/falgy.2022.818732] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 01/14/2022] [Indexed: 01/29/2023] Open
Abstract
Allergens are antigens that generate an IgE response (sensitization) in susceptible individuals. The allergenicity of an allergen can be thought of in terms of its ability to sensitize as well as its ability to cross-link IgE/IgE receptor complexes on mast cells and basophils leading to release of preformed and newly formed mediators (effector activity). The identity of the allergens responsible for sensitization may be different from those that elicit an allergic response. Effector activity is determined by (1) the amount of specific IgE (sIgE) and in some circumstances the ratio of sIgE to total IgE, (2) the number of high affinity receptors for IgE (FcεR1) on the cell surface, (3) the affinity of binding of sIgE for its epitope and, in a polyclonal response, the collective avidity, (4) the number and spatial relationships of IgE binding epitopes on the allergen and (5) the presence of IgG that can bind to allergen and either block binding of sIgE and/or activate low affinity IgG receptors that activate intracellular inhibitory pathways. This review will discuss these important immunologic and physical properties that contribute to the effector activity of allergens.
Collapse
Affiliation(s)
- Stéphane Hazebrouck
- Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SPI, Gif-sur-Yvette, France
| | - Nicole Canon
- Division of Allergy and Clinical Immunology, Department of Medicine, University of Colorado Denver, Aurora, CO, United States
| | - Stephen C. Dreskin
- Division of Allergy and Clinical Immunology, Department of Medicine, University of Colorado Denver, Aurora, CO, United States
| |
Collapse
|
|
17
|
Lange L, Klimek L, Beyer K, Blümchen K, Novak N, Hamelmann E, Bauer A, Merk HF, Rabe U, Jung K, Schlenter WW, Ring J, Chaker AM, Wehrmann W, Becker S, Mülleneisen NK, Nemat K, Czech W, Wrede H, Brehler R, Fuchs T, Jakob T, Ankermann T, Schmidt SM, Gerstlauer M, Zuberbier T, Spindler T, Vogelberg C. White Paper Erdnussallergie - Teil 1: Epidemiologie, Burden of Disease, gesundheitsökonomische Aspekte. ALLERGO JOURNAL 2021. [DOI: 10.1007/s15007-021-4935-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
|
|
18
|
Suárez‐Fariñas M, Suprun M, Kearney P, Getts R, Grishina G, Hayward C, Luta D, Porter A, Witmer M, du Toit G, Lack G, Chinthrajah RS, Galli SJ, Nadeau K, Sampson HA. Accurate and reproducible diagnosis of peanut allergy using epitope mapping. Allergy 2021; 76:3789-3797. [PMID: 33991353 PMCID: PMC8607840 DOI: 10.1111/all.14905] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 04/19/2021] [Accepted: 04/25/2021] [Indexed: 01/18/2023]
Abstract
BACKGROUND Accurate diagnosis of peanut allergy is a significant clinical challenge. Here, a novel diagnostic blood test using the peanut bead-based epitope assay ("peanut BBEA") was developed utilizing the LEAP cohort and then validated using two independent cohorts. METHODS The development of the peanut BBEA diagnostic test followed the National Academy of Medicine's established guidelines with discovery performed on 133 subjects from the non-interventional arm of the LEAP trial and an independent validation performed on 82 subjects from the CoFAR2 and 84 subjects from the POISED study. All samples were analyzed using the peanut BBEA methodology, which measures levels of IgE to two Ara h 2 sequential (linear) epitopes and compares their combination to a threshold pre-specified in the model development phase. When a patient has an inconclusive outcome by skin prick testing (or sIgE), IgE antibody levels to this combination of two epitopes can distinguish whether the patient is "Allergic" or "Not Allergic." Diagnoses of peanut allergy in all subjects were confirmed by double-blind placebo-controlled food challenge and subjects' ages were 7-55 years. RESULTS In the validation using CoFAR2 and POISED cohorts, the peanut BBEA diagnostic test correctly diagnosed 93% of the subjects, with a sensitivity of 92%, specificity of 94%, a positive predictive value of 91%, and negative predictive value of 95%. CONCLUSIONS In validation of the peanut BBEA diagnostic test, the overall accuracy was found to be superior to existing diagnostic tests for peanut allergy including skin prick testing, peanut sIgE, and peanut component sIgE testing.
Collapse
Affiliation(s)
- Mayte Suárez‐Fariñas
- Department of Population Health Science and Policy and Department of Genetics and GenomicsIcahn School of MedicineNew YorkNYUSA
| | - Maria Suprun
- Department of Pediatrics, Allergy and ImmunologyIcahn School of Medicine at Mount SinaiNew YorkNYUSA
| | - Paul Kearney
- AllerGenis LLCHatfieldPAUSA
- Data Incites LLCSeattleWAUSA
| | | | - Galina Grishina
- Department of Pediatrics, Allergy and ImmunologyIcahn School of Medicine at Mount SinaiNew YorkNYUSA
| | | | | | | | | | | | | | | | - Stephen J. Galli
- Sean N. Parker Center for Allergy and Asthma ResearchStanford UniversityStanfordCAUSA
- Departments of Pathology and Microbiology & ImmunologyStanford UniversityStanfordCAUSA
| | - Kari Nadeau
- Sean N. Parker Center for Allergy and Asthma ResearchStanford UniversityStanfordCAUSA
| | - Hugh A. Sampson
- Department of Pediatrics, Allergy and ImmunologyIcahn School of Medicine at Mount SinaiNew YorkNYUSA
| |
Collapse
|
|
19
|
Lange L, Klimek L, Beyer K, Blümchen K, Novak N, Hamelmann E, Bauer A, Merk H, Rabe U, Jung K, Schlenter W, Ring J, Chaker A, Wehrmann W, Becker S, Mülleneisen N, Nemat K, Czech W, Wrede H, Brehler R, Fuchs T, Jakob T, Ankermann T, Schmidt SM, Gerstlauer M, Zuberbier T, Spindler T, Vogelberg C. White paper on peanut allergy - part 1: Epidemiology, burden of disease, health economic aspects. ACTA ACUST UNITED AC 2021; 30:261-269. [PMID: 34603938 PMCID: PMC8477625 DOI: 10.1007/s40629-021-00189-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 06/21/2021] [Indexed: 01/27/2023]
Abstract
Peanuts are Leguminosae, commonly known as the legume or pea family, and peanut allergy is among the most common food allergies and the most common cause of fatal food reactions and anaphylaxis. The prevalence of peanut allergy increased 3.5-fold over the past two decades reaching 1.4–2% in Europe and the United States. The reasons for this increase in prevalence are likely multifaceted. Sensitization via the skin appears to be associated with the development of peanut allergy and atopic eczema in infancy is associated with a high risk of developing peanut allergy. Until recently, the only possible management strategy for peanut allergy was strict allergen avoidance and emergency treatment including adrenaline auto-injector in cases of accidental exposure and reaction. This paper discusses the various factors that impact the risks of peanut allergy and the burden of self-management on peanut-allergic children and their caregivers.
Collapse
Affiliation(s)
- Lars Lange
- Department of Pediatrics, St. Marien-Hospital, GFO Clinics Bonn, Bonn, Germany
| | - Ludger Klimek
- Center for Rhinology and Allergology Wiesbaden, Wiesbaden, Germany
| | - Kirsten Beyer
- Department of Pediatrics m.S. Pneumology, Immunology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Katharina Blümchen
- Center of Pediatric and Adolescent Medicine, Focus on Allergology, Pneumology and Cystic Fibrosis, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt a. M., Germany
| | - Natalija Novak
- Clinic and Polyclinic for Dermatology and Allergology, University Hospital Bonn, Bonn, Germany
| | - Eckard Hamelmann
- Pediatric and Adolescent Medicine, Bethel Children's Center, OWL University Hospital of Bielefeld University, Bielefeld, Germany
| | - Andrea Bauer
- Clinic and Polyclinic for Dermatology, University AllergyCenter, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany
| | - Hans Merk
- Department of Dermatology & Allergology, RWTH Aachen, Aachen, Germany
| | - Uta Rabe
- Clinic for Allergology, Johanniter-Krankenhaus im Fläming Treuenbrietzen GmbH, Treuenbrietzen, Germany
| | - Kirsten Jung
- Practice for Dermatology, Immunology and Allergology, Erfurt, Germany
| | | | | | - Adam Chaker
- Department of Otolaryngology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.,Center for Allergy and Environment (ZAUM), Klinikum rechts der Isar, Technische Universität München, Munich, Germany
| | | | - Sven Becker
- Department of Otolaryngology, University of Tübingen, Tübingen, Germany
| | | | - Katja Nemat
- Pediatric Pneumology/Allergology Practice, Kinderzentrum Dresden (Kid), Dresden, Germany
| | - Wolfgang Czech
- Practice and clinic for allergology/dermatology, Schwarzwald-Baar Klinikum, Villingen-Schwenningen, Germany
| | - Holger Wrede
- Practice and clinic for allergology/ear, nose and throat specialist, Herford, Germany
| | - Randolf Brehler
- Clinic for Skin Diseases, Outpatient Clinic for Allergology, Occupational Dermatology and Environmental Medicine, Münster University Hospital, Münster, Germany
| | - Thomas Fuchs
- Department of Dermatology, Venereology and Allergology, University Hospital, Georg-August-University, Göttingen, Germany
| | - Thilo Jakob
- rd Clinic for Dermatology and Allergology University Hospital Giessen, UKGM Justus Liebig University Giessen, Giessen, Germany
| | - Tobias Ankermann
- th Clinic for Pediatric and Adolescent Medicine, Pneumology, Allergology, Neonatology, Intensive Care Medicine, Infectiology, University Hospital Schleswig-Holstein, Kiel, Germany
| | - Sebastian M Schmidt
- th Center for Pediatric and Adolescent Medicine, Clinic and Polyclinic for Pediatric and Adolescent Medicine, Greifswald University Medical Center, Greifswald, Germany
| | - Michael Gerstlauer
- pediatric pneumologist/pediatric allergologist, II. clinic for children and adolescents, University Hospital Augsburg, Augsburg, Germany
| | - Torsten Zuberbier
- Clinic for Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Thomas Spindler
- Department of Pediatrics and Adolescent Medicine, Pediatric Pneumology, Allergology, Sports Medicine, Hochgebirgsklinik Davos, Davos-Wolfgang, Switzerland
| | - Christian Vogelberg
- TU Dresden/UKDD, Pediatric Department, University Hospital Dresden, Dresden, Germany.,Department of Pediatric Pneumology/Allergology, Clinic and Polyclinic for Pediatrics and Adolescent Medicine, University Hospital Carl Gustav Carus, Fetscher Street 74, 01307 Dresden, Germany
| |
Collapse
|
|
20
|
Fuhrmann V, Huang HJ, Akarsu A, Shilovskiy I, Elisyutina O, Khaitov M, van Hage M, Linhart B, Focke-Tejkl M, Valenta R, Sekerel BE. From Allergen Molecules to Molecular Immunotherapy of Nut Allergy: A Hard Nut to Crack. Front Immunol 2021; 12:742732. [PMID: 34630424 PMCID: PMC8496898 DOI: 10.3389/fimmu.2021.742732] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 08/23/2021] [Indexed: 12/02/2022] Open
Abstract
Peanuts and tree nuts are two of the most common elicitors of immunoglobulin E (IgE)-mediated food allergy. Nut allergy is frequently associated with systemic reactions and can lead to potentially life-threatening respiratory and circulatory symptoms. Furthermore, nut allergy usually persists throughout life. Whether sensitized patients exhibit severe and life-threatening reactions (e.g., anaphylaxis), mild and/or local reactions (e.g., pollen-food allergy syndrome) or no relevant symptoms depends much on IgE recognition of digestion-resistant class I food allergens, IgE cross-reactivity of class II food allergens with respiratory allergens and clinically not relevant plant-derived carbohydrate epitopes, respectively. Accordingly, molecular allergy diagnosis based on the measurement of allergen-specific IgE levels to allergen molecules provides important information in addition to provocation testing in the diagnosis of food allergy. Molecular allergy diagnosis helps identifying the genuinely sensitizing nuts, it determines IgE sensitization to class I and II food allergen molecules and hence provides a basis for personalized forms of treatment such as precise prescription of diet and allergen-specific immunotherapy (AIT). Currently available forms of nut-specific AIT are based only on allergen extracts, have been mainly developed for peanut but not for other nuts and, unlike AIT for respiratory allergies which utilize often subcutaneous administration, are given preferentially by the oral route. Here we review prevalence of allergy to peanut and tree nuts in different populations of the world, summarize knowledge regarding the involved nut allergen molecules and current AIT approaches for nut allergy. We argue that nut-specific AIT may benefit from molecular subcutaneous AIT (SCIT) approaches but identify also possible hurdles for such an approach and explain why molecular SCIT may be a hard nut to crack.
Collapse
Affiliation(s)
- Verena Fuhrmann
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Huey-Jy Huang
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Aysegul Akarsu
- Division of Allergy and Asthma, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Igor Shilovskiy
- Laboratory for Molecular Allergology, National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
| | - Olga Elisyutina
- Laboratory for Molecular Allergology, National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
| | - Musa Khaitov
- Laboratory for Molecular Allergology, National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
- Pirogov Russian National Research Medical University, Moscow, Russia
| | - Marianne van Hage
- Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet and Karolinska University, Hospital, Stockholm, Sweden
| | - Birgit Linhart
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Margarete Focke-Tejkl
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
- Karl Landsteiner University of Health Sciences, Krems, Austria
| | - Rudolf Valenta
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
- Laboratory for Molecular Allergology, National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
- Karl Landsteiner University of Health Sciences, Krems, Austria
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Bulent Enis Sekerel
- Division of Allergy and Asthma, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
| |
Collapse
|
|
21
|
An Updated Overview of Almond Allergens. Nutrients 2021; 13:nu13082578. [PMID: 34444737 PMCID: PMC8399460 DOI: 10.3390/nu13082578] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 07/21/2021] [Accepted: 07/23/2021] [Indexed: 12/19/2022] Open
Abstract
Tree nuts are considered an important food in healthy diets. However, for part of the world’s population, they are one of the most common sources of food allergens causing acute allergic reactions that can become life-threatening. They are part of the Big Eight food groups which are responsible for more than 90% of food allergy cases in the United States, and within this group, almond allergies are persistent and normally severe and life-threatening. Almond is generally consumed raw, toasted or as an integral part of other foods. Its dietary consumption is generally associated with a reduced risk of cardiovascular diseases. Several almond proteins have been recognized as allergens. Six of them, namely Pru du 3, Pru du 4, Pru du 5, Pru du 6, Pru du 8 and Pru du 10, have been included in the WHO-IUIS list of allergens. Nevertheless, further studies are needed in relation to the accurate characterization of the already known almond allergens or putative ones and in relation to the IgE-binding properties of these allergens to avoid misidentifications. In this context, this work aims to critically review the almond allergy problematic and, specifically, to perform an extensive overview regarding known and novel putative almond allergens.
Collapse
|
|
22
|
Dreskin SC, Koppelman SJ, Andorf S, Nadeau KC, Kalra A, Braun W, Negi SS, Chen X, Schein CH. The importance of the 2S albumins for allergenicity and cross-reactivity of peanuts, tree nuts, and sesame seeds. J Allergy Clin Immunol 2021; 147:1154-1163. [PMID: 33217410 PMCID: PMC8035160 DOI: 10.1016/j.jaci.2020.11.004] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 11/06/2020] [Accepted: 11/10/2020] [Indexed: 12/17/2022]
Abstract
Allergies to peanuts, tree nuts, and sesame seeds are among the most important food-related causes of anaphylaxis. Important clinical questions include: Why is there a variable occurrence of coallergy among these foods and Is this immunologically mediated? The clinical and immunologic data summarized here suggest an immunologic basis for these coallergies that is based on similarities among the 2S albumins. Data from component resolved diagnostics have highlighted the relationship between IgE binding to these allergens and the presence of IgE-mediated food allergy. Furthermore, in vitro and in vivo experiments provide strong evidence that the 2S albumins are the most important allergens in peanuts for inducing an allergic effector response. Although the 2S albumins are diverse, they have a common disulfide-linked core with similar physicochemical properties that make them prime candidates to explain much of the observed coallergy among peanuts, tree nuts, and sesame seeds. The well-established frequency of cashew and pistachio nut coallergy (64%-100%) highlights how the structural similarities among their 2S albumins may account for observed clinical cross-reactivity. A complete understanding of the physicochemical properties of the 2S albumins in peanuts, tree nuts, and sesame seeds will enhance our ability to diagnose, treat, and ultimately prevent these allergies.
Collapse
Affiliation(s)
- Stephen C Dreskin
- Division of Allergy and Clinical Immunology, Department of Medicine, University of Colorado Denver, Aurora, Colo.
| | - Stef J Koppelman
- Food Allergy Research and Resource Program, Department of Food Science and Technology, University of Nebraska, Lincoln, Neb
| | - Sandra Andorf
- Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif
| | - Kari C Nadeau
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif
| | - Anjeli Kalra
- Division of Allergy and Clinical Immunology, Department of Medicine, University of Colorado Denver, Aurora, Colo
| | - Werner Braun
- Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch, Galveston, Tex; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, Tex
| | - Surendra S Negi
- Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch, Galveston, Tex; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, Tex
| | - Xueni Chen
- Division of Allergy and Clinical Immunology, Department of Medicine, University of Colorado Denver, Aurora, Colo
| | - Catherine H Schein
- Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, Tex; Institute for Human Infection and Immunity, The University of Texas Medical Branch, Galveston, Tex.
| |
Collapse
|
|
23
|
Midun E, Radulovic S, Brough H, Caubet JC. Recent advances in the management of nut allergy. World Allergy Organ J 2021; 14:100491. [PMID: 33510829 PMCID: PMC7811165 DOI: 10.1016/j.waojou.2020.100491] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 11/02/2020] [Accepted: 11/03/2020] [Indexed: 11/25/2022] Open
Abstract
Peanut/tree nut allergy is common and has been associated with particularly severe reactions. Epidemiological data have shown that the prevalence ranges between 0.05% and 4.9% for tree nut and between 0.5% and 3% for peanut. These large variations can be explained by differences in the age of included patients and the geographical region. In addition, the food consumption modality (ie, raw versus roasted) plays a major role, as heat treatment has the capacity to modify the allergenicity of nuts and legumes. Nut allergies tend to persist into adulthood and consequently have a high impact on quality of life. Recently, it has been demonstrated that a significant proportion of nut allergic patients are able to tolerate other nuts. As opposed to the avoidance of all nuts, this approach is currently proposed in several tertiary allergy centers. However, diagnosis of nut allergy is particularly difficult due to co-sensitization leading to high rate of false positive skin prick tests and/or specific IgE to whole allergen extracts. The use of component resolved diagnosis leads to major improvement of diagnosis, particularly to distinguish between primary and secondary nut allergies. The basophil activation test has been suggested to be useful but is still used mainly as a research tool. Thus, diagnosis remains mainly based on the oral food challenge, which is considered as the gold standard. Regarding treatment, avoidance remains the cornerstone of management of nut allergy. Oral immunotherapy is increasingly proposed as an alternative management strategy.
Collapse
Key Words
- Component-resolved diagnostic, CRD
- Cross reactivity
- Double-blind, placebo-controlled, food challenge, DBPCFC
- Food allergy
- Lipid transfer protein, LTP
- Oral allergy syndrome, OAS
- Oral food challenge, OFC
- Oral immunotherapy
- Oral induction tolerance, OIT
- Pathogenesis related protein type 10, PR-10
- Peanut
- Platelet-activating factor, PAF
- Pollen-food syndrome, PFS
- Precautionary Allergen Labels, (PAL)
- Skin prick test, SPT
- Tree nut
- Tree nut, TN
Collapse
Affiliation(s)
- Elise Midun
- Pediatric Allergy Unit, University Hospitals of Geneva and University of Geneva, Rue Willy Donzé 6, 1205 Geneva, Switzerland, University Lyon 1 Claude Bernard, 43 Boulevard Du 11-Novembre-1918, 69100, Villeurbanne, France
- Corresponding author.
| | - Suzana Radulovic
- Paediatric Allergy Group, Department of Women and Children's Health, King's College London, London, United Kingdom, Paediatric Allergy Group, Peter Gorer Dept of Immunobiology, School of Immunology & Microbial Sciences, King's College London, Guys' Hospital, London, United Kingdom, Children's Allergy Service, Evelina Children's Hospital, Guy's and St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom
| | - Helen Brough
- Paediatric Allergy Group, Department of Women and Children's Health, King's College London, London, United Kingdom, Paediatric Allergy Group, Peter Gorer Dept of Immunobiology, School of Immunology & Microbial Sciences, King's College London, Guys' Hospital, London, United Kingdom, Children's Allergy Service, Evelina Children's Hospital, Guy's and St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom
| | - Jean-Christoph Caubet
- Pediatric Allergy Unit, University Hospitals of Geneva and University of Geneva, Rue Willy Donzé 6, 1205, Geneva, Switzerland
| |
Collapse
|
|
24
|
Smits M, Nooijen I, Redegeld F, de Jong A, Le TM, Knulst A, Houben G, Verhoeckx K. Digestion and Transport across the Intestinal Epithelium Affects the Allergenicity of Ara h 1 and 3 but Not of Ara h 2 and 6. Mol Nutr Food Res 2021; 65:e2000712. [PMID: 33434390 PMCID: PMC8047886 DOI: 10.1002/mnfr.202000712] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 12/04/2020] [Indexed: 12/12/2022]
Abstract
Scope No accepted and validated methods are currently available which can accurately predict protein allergenicity. In this study, the role of digestion and transport on protein allergenicity is investigated. Methods and results Peanut allergens (Ara h 1, 2, 3, and 6) and a milk allergen (β‐lactoglobulin) are transported across pig intestinal epithelium using the InTESTine model and afterward basophil activation is measured to assess the (remaining) functional properties. Additionally, allergens are digested by pepsin prior to epithelial transport and their allergenicity is assessed in a human mast cell activation assay. Remarkably, transported Ara h 1 and 3 are not able to activate basophils, in contrast to Ara h 2 and 6. Digestion prior to transport results in a significant increase in mast cell activation of Ara h 1 and 3 dependent on the length of digestion time. Activation of mast cells by Ara h 2 and 6 is unaffected by digestion prior to transport. Conclusions Digestion and transport influences the allergenicity of Ara h 1 and 3, but not of Ara h 2 and 6. The influence of digestion and transport on protein allergenicity may explain why current in vitro assays are not predictive for allergenicity.
Collapse
Affiliation(s)
- Mark Smits
- The Netherlands Organisation for Applied Scientific Research TNO, Princetonlaan 6, Utrecht, Utrecht, 3584 CB, The Netherlands.,Department of Dermatology/Allergology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, Utrecht, 3584 CX, The Netherlands.,Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, Utrecht, 3584 CX, The Netherlands
| | - Irene Nooijen
- The Netherlands Organisation for Applied Scientific Research TNO, Utrechtseweg 48, Zeist, Utrecht, 3704 HE, The Netherlands
| | - Frank Redegeld
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, Utrecht, Utrecht, 3584 CG, The Netherlands
| | - Aard de Jong
- Wageningen Food & Biobased Research, Bornse Weilanden 9, Wageningen, Gelderland, 6708 WG, The Netherlands.,The Netherlands Organisation for Applied Scientific Research TNO, Utrechtseweg 48, Zeist, Utrecht, 3704 HE, The Netherlands
| | - Thuy-My Le
- Department of Dermatology/Allergology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, Utrecht, 3584 CX, The Netherlands.,Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, Utrecht, 3584 CX, The Netherlands
| | - André Knulst
- Department of Dermatology/Allergology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, Utrecht, 3584 CX, The Netherlands.,Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, Utrecht, 3584 CX, The Netherlands
| | - Geert Houben
- The Netherlands Organisation for Applied Scientific Research TNO, Princetonlaan 6, Utrecht, Utrecht, 3584 CB, The Netherlands.,Department of Dermatology/Allergology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, Utrecht, 3584 CX, The Netherlands.,Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, Utrecht, 3584 CX, The Netherlands
| | - Kitty Verhoeckx
- Department of Dermatology/Allergology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, Utrecht, 3584 CX, The Netherlands.,Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, Utrecht, 3584 CX, The Netherlands.,The Netherlands Organisation for Applied Scientific Research TNO, Utrechtseweg 48, Zeist, Utrecht, 3704 HE, The Netherlands
| |
Collapse
|
|
25
|
Sharma V, Jobrack J, Cerenzia W, Tilles S, Ryan R, Sih-Meynier R, Zeitler S, Manning M. A study to assess current approaches of allergists in European countries diagnosing and managing children and adolescents with peanut allergy. PLoS One 2020; 15:e0241648. [PMID: 33270629 PMCID: PMC7714149 DOI: 10.1371/journal.pone.0241648] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 10/12/2020] [Indexed: 12/05/2022] Open
Abstract
RATIONALE Food allergy is documented to result in considerable morbidity, negative impact on quality of life, and substantial medical care costs. Although anecdotal data suggest widely varying practices in the diagnosis and management of food allergies, the diversity and relative frequency of these practices have not been documented. METHODS A questionnaire was developed evaluating allergists' management approaches of individuals with peanut allergy (PA) in Germany (DE), France (FR), and the United Kingdom (UK). RESULTS Here, we report the survey results from a total of 109 allergists from DE, FR and the UK. They reported to confirm PA at initial diagnosis using skin prick test (≥60%), while allergists from DE and FR reported using allergen-specific IgE testing more (>86%) compared to the UK (<50%). At initial diagnosis, oral food challenge was used less in DE (13%) and FR (14%) and very rarely in the UK (3%) to confirm diagnosis. Recognition of acute reactions, use of adrenaline auto-injectors and allergen avoidance were reported to be discussed with the patient/caregiver at the initial office visit by most allergists (>75%). Half of the responders reported assessing the patient's quality of life. 63% allergists reported retesting for PA resolution at a later date, with 45% allergists indicated to recommend ingestion of a normal serving of peanut regularly upon resolution. Lack of effective PA treatment was reported to be a 'very significant' barrier for optimal PA treatment, with allergists being less than 'moderately familiar' with data from clinical trials testing new treatments options for PA. Lastly, allergists stated that the severity of patient's PA ranked as the most important factor in their decision to recommend oral immunotherapy for PA treatment. CONCLUSIONS This survey provides essential insights into the practice of allergists and highlights some areas that would inform strategies for education and improving PA healthcare.
Collapse
Affiliation(s)
- Vibha Sharma
- Lydia Becker Institute of Immunology and Inflammation University of Manchester and Royal Manchester Children’s Hospital NHS Foundation Trust, Manchester, United Kingdom
| | | | | | - Stephen Tilles
- Medical Affairs, Aimmune Therapeutics, Brisbane, CA, United States of America
- University of Washington, Seattle, WA, United States of America
| | - Robert Ryan
- Aimmune Therapeutics, London, United Kingdom
| | - Regina Sih-Meynier
- Medical Affairs, Aimmune Therapeutics, Brisbane, CA, United States of America
| | | | - Michael Manning
- Medical Research of Arizona, Scottsdale, AZ, United States of America
| |
Collapse
|
|
26
|
Suprun M, Sicherer SH, Wood RA, Jones SM, Leung DYM, Henning AK, Dawson P, Burks AW, Lindblad R, Getts R, Suárez-Fariñas M, Sampson HA. Early epitope-specific IgE antibodies are predictive of childhood peanut allergy. J Allergy Clin Immunol 2020; 146:1080-1088. [PMID: 32795587 PMCID: PMC8095129 DOI: 10.1016/j.jaci.2020.08.005] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 07/31/2020] [Accepted: 08/05/2020] [Indexed: 11/26/2022]
Abstract
BACKGROUND Peanut allergy is characterized by the development of IgE against peanut antigen. OBJECTIVE We sought to evaluate the evolution of epitope-specific (es)IgE and esIgG4 in a prospective cohort of high-risk infants to determine whether antibody profiles can predict peanut allergy after age 4 years. METHODS The end point was allergy status at age 4+ years; samples from 293 children were collected at age 3 to 15 months and 2 to 3 and 4+ years. Levels of specific (s)IgE and sIgG4 to peanut and component proteins, and 50 esIgE and esIgG4 were quantified. Changes were analyzed with mixed-effects models. Machine learning algorithms were developed to identify a combination of antigen- and epitope-specific antibodies that using 3- to 15-month or 2- to 3-year samples can predict allergy status at age 4+ years. RESULTS At age 4+ years, 38% of children were Tolerant or 14% had Possible, 8% Convincing, 24% Serologic, and 16% Confirmed allergy. At age 3 to 15 months, esIgE profiles were similar among groups, whereas marked increases were evident at age 2 and 4+ years only in Confirmed and Serologic groups. In contrast, peanut sIgE level was significantly lower in the Tolerant group at age 3 to 15 months, increased in Confirmed and Serologic groups but decreased in Convincing and Possibly Allergic groups over time. An algorithm combining esIgEs with peanut sIgE outperformed different clinically relevant IgE cutoffs, predicting allergy status on an "unseen" set of patients with area under the curves of 0.84 at age 3 to 15 months and 0.87 at age 2 to 3 years. CONCLUSIONS Early epitope-specific plus peanut-specific IgE is predictive of allergy status at age 4+ years.
Collapse
Affiliation(s)
- Maria Suprun
- Icahn School of Medicine at Mount Sinai, New York, NY
| | | | - Robert A Wood
- Johns Hopkins University School of Medicine, Baltimore, Md
| | - Stacie M Jones
- University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, Ark
| | | | | | | | | | | | | | | | | |
Collapse
|
|
27
|
Zhang Y, Jin T. Almond allergens: update and perspective on identification and characterization. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2020; 100:4657-4663. [PMID: 32270879 DOI: 10.1002/jsfa.10417] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 04/01/2020] [Accepted: 04/09/2020] [Indexed: 06/11/2023]
Abstract
Almond (Prunus dulcis) is not only widely used as a human food as a result of its flavor, nutrients, and health benefits, but it is also one of the most likely tree nuts to trigger allergies. Almond allergens, however, have not been studied as extensively as those of peanuts and other selected tree nuts. This review provides an update of the molecular properties of almond allergens to clarify some confusion about the identities of almond allergens and our perspective on characterizing putative almond allergens. At present, the following almond allergens have been designated by the World Health Organization/International Union of Immunological Societies Allergen Nomenclature Sub-Committee: Pru du 3 (a non-specific lipid transfer protein 1, nsLTP1), Pru du 4 (a profilin), Pru du 5 (60S acidic ribosomal protein 2), Pru du 6 (an 11S legumin known as prunin) and Pru du 8 (an antimicrobial protein with cC3C repeats). Besides, almond vicilin and almond γ-conglutin have been identified as food allergens, although further characterization of these allergens is still of interest. In addition, almond 2S albumin was reported as a food allergen as a result of the misidentification of Pru du 8. Two more almond proteins have been called allergens based on their sequence homology with known food allergens and their 'membership' in relevant protein families that contain allergens in many species. These include the pathogenesis related-10 protein (referred to as Pru du 1) and the thaumatin-like protein (referred to as Pru du 2). Almonds thus have five known food allergens and five more likely ones that need to be investigated further. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.
Collapse
Affiliation(s)
- Yuzhu Zhang
- U.S. Department of Agriculture, Agricultural Research Service, Pacific West Area, Western Regional Research Center, Albany, CA, USA
| | - Tengchuan Jin
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| |
Collapse
|
|
28
|
Kaur N, Mehr S, Katelaris C, Wainstein B, Altavilla B, Saad R, Valerio C, Codarini M, Burton P, Perram F, Baumgart K, Barnes EH, Campbell DE. Added Diagnostic Value of Peanut Component Testing: A Cross-Sectional Study in Australian Children. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2020; 9:245-253.e4. [PMID: 32942048 DOI: 10.1016/j.jaip.2020.08.060] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Revised: 08/26/2020] [Accepted: 08/27/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND Peanut components are widely used in clinical practice; however, their utility to predict challenge outcome in the Australian children, outside of infants, is not well studied. OBJECTIVE Can peanut component testing predict outcome of challenge in peanut-allergic children. METHODS All children attending peanut challenges, regardless of previous allergic reactions to peanut or sensitization (skin prick test or peanut IgE) alone, were recruited. Serum collected before the challenge was analyzed for peanut IgE and Ara h 1, 2, 3, 6, 8, and 9 (ImmunoCap). RESULTS Of the 222 children recruited, 89 (40%) were allergic on oral food challenge. Ara h 2 and 6 performed similarly to peanut IgE and skin prick test in predicting challenge outcome (area under the curve, 0.84-0.87). No baseline clinical characteristics, including past history, predicted challenge outcome. By logistic regression, degree of polysensitization to Ara h 1, 2, or 3 increased the odds of allergic reaction at oral food challenge at 0.35 and 1.0 kUA/L cutoff levels (P < .001 for both). All 11 children sensitized (>0.35 kUA/L) to Ara h 1, 2, and 3 reacted to peanut challenge. Degree of polysensitization at more than 1.0 kUA/L was associated with a lower cumulative eliciting dose (P = .016) and with severity of allergic reaction on challenge (P = .007). CONCLUSIONS In our cohort, sensitization to the combination of Ara h 1, 2, and 3 was highly predictive of peanut allergy. Overall, only Ara h 2 as individual component most correlated with severity of reaction at challenge and adrenaline use. Ara h 8 and 9 were not useful in predicting challenge outcome.
Collapse
Affiliation(s)
- Narinder Kaur
- Department of Allergy and Immunology, The Children's Hospital at Westmead, SCHN, Sydney, NSW, Australia; Sydney Child Health Program, Sydney Children's Hospitals Network, Sydney, NSW, Australia
| | - Sam Mehr
- Department of Allergy and Immunology, The Children's Hospital at Westmead, SCHN, Sydney, NSW, Australia
| | - Constance Katelaris
- Camden and Campbelltown Hospital, Sydney, NSW, Australia; School of Medicine, Western Sydney University, Sydney, NSW, Australia
| | - Brynn Wainstein
- Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick, Sydney, NSW, Australia; School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia
| | - Betina Altavilla
- Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick, Sydney, NSW, Australia
| | - Rebecca Saad
- Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick, Sydney, NSW, Australia
| | - Carolina Valerio
- Department of Allergy and Immunology, The Children's Hospital at Westmead, SCHN, Sydney, NSW, Australia
| | - Miriam Codarini
- Camden and Campbelltown Hospital, Sydney, NSW, Australia; School of Medicine, Western Sydney University, Sydney, NSW, Australia
| | - Pamela Burton
- Camden and Campbelltown Hospital, Sydney, NSW, Australia
| | - Fiona Perram
- Camden and Campbelltown Hospital, Sydney, NSW, Australia
| | - Karl Baumgart
- Immunology, Douglass Hanly Moir Pathology, Sydney, NSW, Australia
| | - Elizabeth H Barnes
- NHMRC Clinical Trials Centre, Sydney Medical School, Sydney University, Sydney, NSW, Australia
| | - Dianne E Campbell
- Department of Allergy and Immunology, The Children's Hospital at Westmead, SCHN, Sydney, NSW, Australia; Faculty of Medicine and Health, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
| |
Collapse
|
|
29
|
Johnson J, Malinovschi A, Lidholm J, Petersson CJ, Nordvall L, Janson C, Alving K, Borres MP. Sensitization to storage proteins in peanut and hazelnut is associated with higher levels of inflammatory markers in asthma. Clin Mol Allergy 2020; 18:11. [PMID: 32581655 PMCID: PMC7310284 DOI: 10.1186/s12948-020-00126-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 06/16/2020] [Indexed: 11/10/2022] Open
Abstract
Background Sensitization to peanuts and hazelnuts is common among young asthmatics and can be primary or a result of cross-reactivity. Sensitization as a result of cross-reactivity to birch pollen is typically associated to tolerance or mild and local symptoms upon intake of peanut or hazelnut. Aim The aim of this study was to investigate relationships between IgE antibody responses against peanut and hazelnut components, airway and systemic inflammation markers, lung function parameters and reported food hypersensitivity in a cohort of asthmatic children and young adults. Methods A population of 408 asthmatic individuals aged 10-35 years were investigated. Information on hypersensitivity symptoms upon intake of peanut or hazelnut were recorded in a standardized questionnaire. Fraction of exhaled nitric oxide (FeNO), blood eosinophil count (B-Eos), spirometry, methacholine challenge outcome and IgE antibodies to peanut and hazelnut allergens were measured by standard clinical and laboratory methods. Results Subjects sensitized to any of the peanut (Ara h 1, 2 or 3) or hazelnut (Cor a 9 or 14) storage proteins were significantly younger (17.6 vs 21.2 years), had higher levels of FeNO (23.2 vs 16.7 ppb) and B-Eos (340 vs 170 cells/mcl) than those displaying only pollen-related cross-reactive sensitization. Levels of FeNO correlated with levels of IgE to storage proteins in children, but not in adults. Levels of B-Eos correlated with levels of IgE to all allergen components investigated in children, but only to levels of IgE to storage proteins in adults. Anaphylaxis and skin reactions upon intake of peanuts or hazelnuts were more often reported among subjects sensitized to the respective storage proteins than among those with only pollen-related cross-reactive sensitization. As compared to peanut, hazelnut was more often reported to cause gastrointestinal symptoms and less often oral cavity symptoms. Conclusions Sensitization to peanut and hazelnut storage proteins was associated with higher levels of inflammation markers and food hypersensitivity symptoms in this population of subjects with asthma.
Collapse
Affiliation(s)
- Jennifer Johnson
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
| | - Andrei Malinovschi
- Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden
| | | | | | - Lennart Nordvall
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
| | - Christer Janson
- Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden
| | - Kjell Alving
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
| | - Magnus P Borres
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.,Thermo Fisher Scientific, Uppsala, Sweden
| |
Collapse
|
|
30
|
Frith K, Katelaris CH. Current perspectives on peanut allergy. Intern Med J 2020; 49:1480-1487. [PMID: 31808255 DOI: 10.1111/imj.14658] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 09/11/2019] [Accepted: 09/15/2019] [Indexed: 12/18/2022]
Abstract
Peanut allergy is increasingly prevalent and for most patients is a life-long condition, with the potential to cause life-threatening reactions. Accurate diagnosis and appropriate management are essential to minimise risks due to accidental peanut exposure. Current management strategies focus on strict allergen avoidance and access to emergency medicines to treat potential reactions; however, active approaches are an area of intense research. Promising new methods of food allergen immunotherapy are set to change the approach to managing peanut allergic patients in the near future.
Collapse
Affiliation(s)
- Katie Frith
- Department of Immunology and Infectious Diseases, Sydney Children's Hospital and University of New South Wales, Sydney, New South Wales, Australia
| | - Constance H Katelaris
- Department of Immunology, Campbelltown Hospital and Western Sydney University, Sydney, New South Wales, Australia
| |
Collapse
|
|
31
|
Bavaro SL, Orlando A, De Angelis E, Russo F, Monaci L. Investigation on the allergen profile of the soluble fraction of autoclaved peanuts and its interaction with Caco-2 cells. Food Funct 2019; 10:3615-3625. [PMID: 31162510 DOI: 10.1039/c9fo00309f] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Peanuts are a source of proteins and fats but they are also considered a harmful food for individuals who are allergic to them due to their ability to trigger severe and life-threatening reactions. Strict avoidance of peanuts is the most effective means to prevent the development of an allergic reaction. Physical or chemical strategies employing autoclaving can represent a valid alternative to produce a final food with a decreased allergenic power as in the case of peanuts. Thermal processing might induce protein modifications in foods and affect protein digestibility or absorption of nutrients across the intestinal mucosa. Besides, the type of processing could also alter food protein allergenicity thus influencing the interplay with the biological system at the gut level. In this paper, we investigated the influence of autoclaving based treatments on the proliferation of epithelial cells at the intestinal level. Extractable proteins of raw and autoclaved peanuts were analysed by SDS-PAGE and untargeted LC-high resolution-MS/MS to investigate the peptide composition. Our findings show that when raw peanuts were assayed on Caco 2 cell lines, an antiproliferative effect was observed. By contrast, peanuts subjected to hydration and autoclaving did not show an inhibition of proliferation on Caco-2 cells. In parallel, extensive fragmentation induced by autoclaving treatments on the original peanut proteins was also recorded by LC-MS/MS analysis with a consequent increase in the number of peptides detected. These results indicate that the processing applied to peanuts can have an influence on both the nutritional and allergological sides, and more investigations will be required on this issue to understand the alteration of inflammatory mediators induced by the treatment applied.
Collapse
Affiliation(s)
- Simona L Bavaro
- Institute of Sciences of Food Production, Italian National Research Council (ISPA-CNR), Via Amendola 122/O, 70126, Bari, Italy.
| | | | | | | | | |
Collapse
|
|
32
|
Dreskin SC, Germinaro M, Reinhold D, Chen X, Vickery BP, Kulis M, Burks AW, Negi SS, Braun W, Chambliss JM, Eglite S, McNulty CMG. IgE binding to linear epitopes of Ara h 2 in peanut allergic preschool children undergoing oral Immunotherapy. Pediatr Allergy Immunol 2019; 30:817-823. [PMID: 31437325 PMCID: PMC6906227 DOI: 10.1111/pai.13117] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Revised: 07/10/2019] [Accepted: 07/31/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND For patients with peanut allergy, there are currently no methods to predict who will develop sustained unresponsiveness (SU) after oral immunotherapy (OIT). OBJECTIVE Assess IgE binding to peanut (PN), Ara h 2, and specific linear epitopes of Ara h 2 as predictors of the important clinical parameters: eliciting dose threshold and attainment of SU following OIT. METHODS Samples and clinical data were collected from children undergoing OIT. PN- and Ara h 2-sIgE were quantified by ImmunoCAP® . IgE binding to linear peptides of Ara h 2 and Ara h 6 was measured with peptide microarrays. RESULTS Values of PN-sIgE correlated with eliciting dose (P = .001) and with a higher likelihood of achieving SU (P < .0001), but these relationships were lost at higher values for PN-sIgE (≥14 kIU for eliciting dose and ≥35 kIU/L for SU). In subjects with PN-sIgE ≥ 14 kIU/L, binding of IgE to epitopes 5 and 6 of Ara h 2 was associated with a lower eliciting dose at baseline challenge (P < .001; Pc < .02). In subjects with PN-sIgE ≥ 35 kIU/L, a combined model of IgE binding to epitopes 1, 5 and 6 with PN-sIgE was highly predictive of attainment of SU (AUC of 0.86; P = .0067). CONCLUSION In young patients with peanut allergy, measurement of PN-sIgE and IgE binding to specific linear epitopes of Ara h 2 in baseline samples may allow stratification of patients regarding sensitivity to challenge and outcome of OIT.
Collapse
Affiliation(s)
- Stephen C Dreskin
- Division of Allergy and Clinical Immunology, Departments of Medicine and Immunology, University of Colorado Denver, Aurora, CO, USA
| | | | | | - Xueni Chen
- Division of Allergy and Clinical Immunology, Departments of Medicine and Immunology, University of Colorado Denver, Aurora, CO, USA
| | - Brian P Vickery
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
| | - Michael Kulis
- Division of Allergy and Immunology, Department of Pediatrics, University of North Carolina-Chapel Hill, NC, USA
| | - A Wesley Burks
- Division of Allergy and Immunology, Department of Pediatrics, University of North Carolina-Chapel Hill, NC, USA
| | - Surendra S Negi
- Sealy Center for Structural Biology and Molecular Biophysics, Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, USA
| | - Werner Braun
- Sealy Center for Structural Biology and Molecular Biophysics, Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, USA
| | - Jeffery M Chambliss
- Division of Allergy and Immunology, Department of Pediatrics, University of Texas, Dallas, TX, USA
| | - Spodra Eglite
- Division of Allergy and Clinical Immunology, Departments of Medicine and Immunology, University of Colorado Denver, Aurora, CO, USA
| | | |
Collapse
|
|
33
|
Hilu KW, Friend SA, Vallanadu V, Brown AM, Hollingsworth LR, Bevan DR. Molecular evolution of genes encoding allergen proteins in the peanuts genus Arachis: Structural and functional implications. PLoS One 2019; 14:e0222440. [PMID: 31675366 PMCID: PMC6824556 DOI: 10.1371/journal.pone.0222440] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Accepted: 08/29/2019] [Indexed: 12/14/2022] Open
Abstract
Food allergies are severe immune responses to plant and animal products mediated by immunoglobulin E (IgE). Peanuts (Arachis hypogaea L.) are among the top 15 crops that feed the world. However, peanuts is among the "big eight food allergens", and allergies induced by peanuts are a significant public health problem and a life-threatening concern. Targeted mutation studies in peanuts demonstrate that single residue alterations in these allergen proteins could result in substantial reduction in allergenicity. Knowledge of peanut allergen proteins is confined to the allotetraploid crop and its two progenitors. We explored frequencies and positions of natural mutations in the hyperallergenic homologues Ara h 2 and Ara h 6 in newly generated sequences for 24 Arachis wild species and the crop species, assessed potential mutational impact on allergenicity using immunoblots and structural modeling, and evaluated whether these mutations follow evolutionary trends. We uncovered a wealth of natural mutations, both substitutions and gaps, including the elimination of immunodominant epitopes in some species. These molecular alterations appear to be associated with substantial reductions in allergenicity. The study demonstrated that Ara h 2 and Ara h 6 follow contrasting modes of natural selection and opposing mutational patterns, particularly in epitope regions. Phylogenetic analysis revealed a progressive trend towards immunodominant epitope evolution in Ara h 2. The findings provide valuable insight into the interactions among mutations, protein structure and immune system response, thus presenting a valuable platform for future manipulation of allergens to minimize, treat or eliminate allergenicity. The study strongly encourages exploration of genepools of economically important plants in allergenicity research.
Collapse
Affiliation(s)
- Khidir W. Hilu
- Department of Biological Sciences, Virginia Tech, Blacksburg, VA, United States of America
| | - Sheena A. Friend
- Department of Biological Sciences, Virginia Tech, Blacksburg, VA, United States of America
| | - Viruthika Vallanadu
- Department of Biological Sciences, Virginia Tech, Blacksburg, VA, United States of America
| | - Anne M. Brown
- Research and Informatics, Virginia Tech, Blacksburg, VA, United States of America
- Department of Biochemistry, Virginia Tech, Blacksburg, VA, United States of America
| | | | - David R. Bevan
- Department of Biochemistry, Virginia Tech, Blacksburg, VA, United States of America
| |
Collapse
|
|
34
|
Yu J, Mikiashvili N. Effectiveness of different proteases in reducing allergen content and IgE-binding of raw peanuts. Food Chem 2019; 307:125565. [PMID: 31630022 DOI: 10.1016/j.foodchem.2019.125565] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 08/30/2019] [Accepted: 09/17/2019] [Indexed: 12/20/2022]
Abstract
The effectiveness of some non-specific proteases in reducing raw peanut allergenicity was investigated. Peanut kernels were treated by Alcalase, papain, Neutrase and bromelain, respectively. The residues of major peanut allergens Ara h 1, Ara h 2 and Ara h 6 were determined by sandwich ELISA and SDS-PAGE, and the allergenicities of treated peanuts were compared to that of untreated peanuts by western blot. All tested proteases were effective in reducing Ara h 1, but their effectiveness in hydrolyzing Ara h 2 and Ara h 6 varied greatly. The maximal reductions of extractable Ara h 1, Ara h 2 and Ara h 6 were 100%, 100% and 99.8%, respectively, achieved by Alcalase hydrolysis. Alcalase was more effective in overall allergenicity reduction; bromelain and Neutrase were the least effective in reducing Ara h 2 and Ara h 6, respectively. The hydrolysis of original allergens also produced some smaller peptides with strong IgE-binding.
Collapse
Affiliation(s)
- Jianmei Yu
- Department of Family and Consumer Sciences, North Carolina Agricultural and Technical State University, Greensboro, NC, USA.
| | - Nona Mikiashvili
- Department of Family and Consumer Sciences, North Carolina Agricultural and Technical State University, Greensboro, NC, USA
| |
Collapse
|
|
35
|
Liao S, Patil SU, Shreffler WG, Dreskin SC, Chen X. Human monoclonal antibodies to Ara h 2 inhibit allergen-induced, IgE-mediated cell activation. Clin Exp Allergy 2019; 49:1154-1157. [PMID: 31134696 DOI: 10.1111/cea.13442] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 04/15/2019] [Accepted: 04/24/2019] [Indexed: 11/30/2022]
Affiliation(s)
- Sumei Liao
- Division of Allergy and Clinical Immunology, Departments of Medicine and Immunology, University of Colorado Denver, Aurora, Colorado
| | - Sarita U Patil
- Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, The Food Allergy Center, Boston, Massachusetts.,General Hospital and MassGeneral Hospital for Children, Boston, Massachusetts
| | - Wayne G Shreffler
- Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, The Food Allergy Center, Boston, Massachusetts.,General Hospital and MassGeneral Hospital for Children, Boston, Massachusetts
| | - Stephen C Dreskin
- Division of Allergy and Clinical Immunology, Departments of Medicine and Immunology, University of Colorado Denver, Aurora, Colorado
| | - Xueni Chen
- Division of Allergy and Clinical Immunology, Departments of Medicine and Immunology, University of Colorado Denver, Aurora, Colorado
| |
Collapse
|
|
36
|
Hazebrouck S, Guillon B, Paty E, Dreskin SC, Adel-Patient K, Bernard H. Variable IgE cross-reactivity between peanut 2S-albumins: The case for measuring IgE to both Ara h 2 and Ara h 6. Clin Exp Allergy 2019; 49:1107-1115. [PMID: 31108010 DOI: 10.1111/cea.13432] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Revised: 04/15/2019] [Accepted: 04/25/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND 2S-albumins Ara h 2 and Ara h 6 are the most potent peanut allergens and levels of specific immunoglobulin E (IgE) towards these proteins are good predictors of clinical reactivity. Because of structural homologies, Ara h 6 is generally considered to cross-react extensively with Ara h 2. OBJECTIVE We aimed to quantify the IgE cross-reactivity between Ara h 2 and Ara h 6. METHODS Peanut 2S-albumins were purified from raw peanuts. The IgE cross-reactivity between Ara h 2 and Ara h 6 was evaluated with 32 sera from French and US peanut-allergic patients by measuring the residual IgE-binding to one 2S-albumin after depletion of IgE antibodies recognizing the other 2S-albumin. The IgE cross-reactivity between Ara h 2 and Ara h 6 was further investigated by competitive inhibition of IgE-binding and by a model of mast cell degranulation. RESULTS A highly variable level of IgE cross-reactivity was revealed among the patients. The mean fraction of cross-reactive IgE antibodies represented only 17.1% of 2S-albumins-specific IgE antibodies and was lower than the mean fraction of IgE specific to Ara h 2 (57.4%) or to Ara h 6 (25.5%). The higher level of Ara h 2-specific IgE was principally due to the IgE-binding capacity of an insertion containing the repeated immunodominant linear epitope DPYSPOH S. The impact of IgE cross-reactivity on diagnostic testing was illustrated with a serum displaying an Ara h 6-specific IgE response of 26 UI/mL that was not associated with the capacity of Ara h 6 to trigger mast cell degranulation. CONCLUSIONS & CLINICAL RELEVANCE Immunoglobulin E antibodies specific to peanut 2S-albumins are mainly non-cross-reactive, but low-affinity cross-reactivity can affect diagnostic accuracy. Testing IgE-binding to a mixture of 2S-albumins rather than to each separately may enhance diagnostic performance.
Collapse
Affiliation(s)
- Stéphane Hazebrouck
- Service de Pharmacologie et Immunoanalyse (SPI), Laboratoire d'Immuno-Allergie Alimentaire, CEA, INRA, Université Paris-Saclay, Gif-sur-Yvette, France
| | - Blanche Guillon
- Service de Pharmacologie et Immunoanalyse (SPI), Laboratoire d'Immuno-Allergie Alimentaire, CEA, INRA, Université Paris-Saclay, Gif-sur-Yvette, France
| | - Evelyne Paty
- Université Paris Descartes-Assistance Publique des Hôpitaux de Paris, Hôpital Necker Enfants Malades, Paris, France
| | - Stephen C Dreskin
- Division of Allergy and Clinical Immunology, Department of Medicine, Denver School of Medicine, University of Colorado, Aurora, Colorado
| | - Karine Adel-Patient
- Service de Pharmacologie et Immunoanalyse (SPI), Laboratoire d'Immuno-Allergie Alimentaire, CEA, INRA, Université Paris-Saclay, Gif-sur-Yvette, France
| | - Hervé Bernard
- Service de Pharmacologie et Immunoanalyse (SPI), Laboratoire d'Immuno-Allergie Alimentaire, CEA, INRA, Université Paris-Saclay, Gif-sur-Yvette, France
| |
Collapse
|
|
37
|
Brusca I, Barrale M, Onida R, La Chiusa SM, Gjomarkaj M, Uasuf CG. The extract, the molecular allergen or both for the in vitro diagnosis of peach and peanut sensitization? Clin Chim Acta 2019; 493:25-30. [DOI: 10.1016/j.cca.2019.01.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2018] [Revised: 01/20/2019] [Accepted: 01/20/2019] [Indexed: 01/02/2023]
|
|
38
|
Kleij HPM, Warmenhoven HJM, Ree R, Versteeg SA, Pieters RHH, Dreskin SC, Knulst AC, Hoffen E, Opstelten DJE, Koppelman SJ, Smit JJ. Chemically modified peanut extract shows increased safety while maintaining immunogenicity. Allergy 2019; 74:986-995. [PMID: 30506686 DOI: 10.1111/all.13687] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Revised: 10/28/2018] [Accepted: 11/16/2018] [Indexed: 01/14/2023]
Abstract
BACKGROUND Peanuts are most responsible for food-induced anaphylaxis in adults in developed countries. An effective and safe immunotherapy is urgently needed. The aim of this study was to investigate the immunogenicity, allergenicity, and immunotherapeutic efficacy of a well-characterized chemically modified peanut extract (MPE) adsorbed to Al(OH)3 . METHODS Peanut extract (PE) was modified by reduction and alkylation. Using sera of peanut-allergic patients, competitive IgE-binding assays and mediator release assays were performed. The immunogenicity of MPE was evaluated by measuring activation of human PE-specific T-cell lines and the induction of PE-specific IgG in mice. The safety and efficacy of MPE adsorbed to Al(OH)3 was tested in two mouse models by measuring allergic manifestations upon peanut challenge in peanut-allergic mice. RESULTS Compared to PE, the IgE-binding and capacity to induce allergic symptoms of MPE were lower in all patients. PE and MPE displayed similar immunogenicity in vivo and in vitro. In mice sensitized to PE, the threshold for anaphylaxis (drop in BT) upon subcutaneous challenge with PE was 0.01 mg, while at 0.3 mg MPE no allergic reaction occurred. Anaphylaxis was not observed when PE and MPE were fully adsorbed to Al(OH)3 . Both PE and MPE + Al(OH)3 showed to be efficacious in a model for immunotherapy. CONCLUSION In our studies, an Al(OH)3 adsorbed MPE showed reduced allergenicity compared to unmodified PE, while the efficacy of immunotherapy is maintained. The preclinical data presented in this study supports further development of modified peanut allergens for IT.
Collapse
Affiliation(s)
| | | | - Ronald Ree
- Department of Experimental Immunology Academic Medical Center University of Amsterdam Amsterdam The Netherlands
- Department of Otorhinolaryngology Academic Medical Center University of Amsterdam AmsterdamThe Netherlands
| | - Serge A. Versteeg
- Department of Experimental Immunology Academic Medical Center University of Amsterdam Amsterdam The Netherlands
| | - Raymond H. H. Pieters
- Institute for Risk Assessment Sciences Immunotoxicology Utrecht University Utrecht The Netherlands
| | - Stephen C. Dreskin
- Division of Allergy and Clinical Immunology Department of Medicine Denver School of Medicine University of Colorado Aurora Colorado
| | - André C. Knulst
- Department Dermatology/Allergology University Medical Center Utrecht Utrecht University Utrecht The Netherlands
| | - Els Hoffen
- Department Dermatology/Allergology University Medical Center Utrecht Utrecht University Utrecht The Netherlands
| | | | | | - Joost J. Smit
- Institute for Risk Assessment Sciences Immunotoxicology Utrecht University Utrecht The Netherlands
| |
Collapse
|
|
39
|
Designer covalent heterobivalent inhibitors prevent IgE-dependent responses to peanut allergen. Proc Natl Acad Sci U S A 2019; 116:8966-8974. [PMID: 30962381 PMCID: PMC6500160 DOI: 10.1073/pnas.1820417116] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Allergies are a result of allergen proteins cross-linking allergen-specific IgE (sIgE) on the surface of mast cells and basophils. The diversity and complexity of allergen epitopes, and high-affinity of the sIgE-allergen interaction have impaired the development of allergen-specific inhibitors of allergic responses. This study presents a design of food allergen-specific sIgE inhibitors named covalent heterobivalent inhibitors (cHBIs) that selectively form covalent bonds to only sIgEs, thereby permanently inhibiting them. Using screening reagents termed nanoallergens, we identified two immunodominant epitopes in peanuts that were common in a population of 16 allergic patients. Two cHBIs designed to inhibit only these two epitopes completely abrogated the allergic response in 14 of the 16 patients in an in vitro assay and inhibited basophil activation in an allergic patient ex vivo analysis. The efficacy of the cHBI design has valuable clinical implications for many allergen-specific responses and more broadly for any antibody-based disease.
Collapse
|
|
40
|
Abstract
PURPOSE OF REVIEW To assess the recent studies that focus on specific immunoglobulin E (sIgE) testing and basophil activation test (BAT) for diagnosing IgE-mediated food allergies. RECENT FINDINGS The sIgE to allergen extract or component can predict reactivity to food. The cutoff value based on the positive predictive value (PPV) of sIgE can be considered whenever deciding whether oral food challenge (OFC) is required to diagnose hen's egg, cow's milk, wheat, peanut, and cashew nut allergy. However, PPV varies depending on the patients' background, OFC methodology, challenge foods, and assay methodology. Component-resolved diagnostics (CRD) has been used for food allergy diagnosis. Ovomucoid and omega-5 gliadin are good diagnostic markers for heated egg and wheat allergy. More recently, CRD of peanut, tree nuts, and seed have been investigated. Ara h 2 showed the best diagnostic accuracy for peanut allergy; other storage proteins, such as Jug r 1 for walnut, Ana o 3 for cashew nut, Ses i 1 for sesame, and Fag e 3 for buckwheat, are also better markers than allergen extracts. Some studies suggested that BAT has superior specificity than skin prick test and sIgE testing. SUMMARY The sIgE testing and BAT can improve diagnostic accuracy. CRD provides additional information that can help determine whether OFCs should be performed to diagnose food allergy.
Collapse
|
|
41
|
Zambrano Ibarra G, Fuentes Aparicio V, Infante Herrero S, Blanca M, Zapatero Remon L. Peanut Allergy in Spanish Children: Comparative Profile of Peanut Allergy versus Tolerance. Int Arch Allergy Immunol 2019; 178:370-376. [DOI: 10.1159/000495579] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 11/19/2018] [Indexed: 11/19/2022] Open
|
|
42
|
Plundrich NJ, Cook BT, Maleki SJ, Fourches D, Lila MA. Binding of peanut allergen Ara h 2 with Vaccinium fruit polyphenols. Food Chem 2019; 284:287-295. [PMID: 30744860 DOI: 10.1016/j.foodchem.2019.01.081] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 01/08/2019] [Accepted: 01/08/2019] [Indexed: 01/30/2023]
Abstract
The potential for 42 different polyphenols found in Vaccinium fruits to bind to peanut allergen Ara h 2 and inhibit IgE binding epitopes was investigated using cheminformatics techniques. Out of 12 predicted binders, delphinidin-3-glucoside, cyanidin-3-glucoside, procyanidin C1, and chlorogenic acid were further evaluated in vitro. Circular dichroism, UV-Vis spectroscopy, and immunoblotting determined their capacity to (i) bind to Ara h 2, (ii) induce protein secondary structural changes, and (iii) inhibit IgE binding epitopes. UV-Vis spectroscopy clearly indicated that procyanidin C1 and chlorogenic acid interacted with Ara h 2, and circular dichroism results suggested that interactions with these polyphenols resulted in changes to Ara h 2 secondary structures. Immunoblotting showed that procyanidin C1 and chlorogenic acid bound to Ara h 2 significantly decreased the IgE binding capacity by 37% and 50%, respectively. These results suggest that certain polyphenols can inhibit IgE recognition of Ara h 2 by obstructing linear IgE epitopes.
Collapse
Affiliation(s)
- Nathalie J Plundrich
- Plants for Human Health Institute, Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, North Carolina Research Campus, Kannapolis, NC 28081, USA
| | - Bethany T Cook
- Department of Chemistry, Bioinformatics Research Center, North Carolina State University, Raleigh, NC 27695, USA
| | - Soheila J Maleki
- United States Department of Agriculture-Agricultural Research Service-Southern Regional Research Center, New Orleans, LA 70124, USA
| | - Denis Fourches
- Department of Chemistry, Bioinformatics Research Center, North Carolina State University, Raleigh, NC 27695, USA
| | - Mary Ann Lila
- Plants for Human Health Institute, Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, North Carolina Research Campus, Kannapolis, NC 28081, USA.
| |
Collapse
|
|
43
|
Croote D, Darmanis S, Nadeau KC, Quake SR. High-affinity allergen-specific human antibodies cloned from single IgE B cell transcriptomes. Science 2019; 362:1306-1309. [PMID: 30545888 DOI: 10.1126/science.aau2599] [Citation(s) in RCA: 151] [Impact Index Per Article: 25.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Accepted: 10/19/2018] [Indexed: 12/21/2022]
Abstract
Immunoglobulin E (IgE) antibodies protect against helminth infections but can also cause life-threatening allergic reactions. Despite their role in human health, the cells that produce these antibodies are rarely observed and remain enigmatic. We isolated single IgE B cells from individuals with food allergies and used single-cell RNA sequencing to elucidate the gene expression and splicing patterns unique to these cells. We identified a surprising example of convergent evolution in which IgE antibodies underwent identical gene rearrangements in unrelated individuals. Through the acquisition of variable region mutations, these IgE antibodies gained high affinity and unexpected cross-reactivity to the clinically important peanut allergens Ara h 2 and Ara h 3. These findings provide insight into IgE B cell transcriptomics and enable biochemical dissection of this antibody class.
Collapse
Affiliation(s)
- Derek Croote
- Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
| | | | - Kari C Nadeau
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA 94305, USA.,Department of Medicine, Stanford University, Stanford, CA 94305, USA.,Department of Pediatrics, Stanford University, Stanford, CA 94305, USA
| | - Stephen R Quake
- Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. .,Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.,Department of Applied Physics, Stanford University, Stanford, CA 94305, USA
| |
Collapse
|
|
44
|
Brian M. Preparation of Samples for a Mass Spectrometry-Based Method to Identify Allergenic Proteins. Methods Mol Biol 2019; 2020:223-237. [PMID: 31177504 DOI: 10.1007/978-1-4939-9591-2_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Western blotting is an immunological technique that has been combined with mass spectrometry analysis, to create a high-throughput method for protein identification. Western blotting using serum allows us to identify a protein within an allergenic extract that specifically binds to a serum antibody, immunoglobulin E. This specific IgE binding protein can then be detected with a highly sensitive chemiluminescence detection substrate.Proteins detected by western blotting can be analyzed by mass spectrometry following an in-gel digestion protocol. The protein band of interest is excised from the gel and digested with trypsin to form peptides. Mass spectrometry will almost certainly have a pre-chromatographic step in which these peptides are separated before becoming ionized and entering a mass analyzer. It is in the mass analyzer that peptides are identified according to their mass-to-charge ratio, compiled into a mass spectrum which is compared to mass spectra held within online protein databases.
Collapse
Affiliation(s)
- Mary Brian
- Department of Occupational and Environmental Medicine, NHLI at Imperial College, London, UK.
| |
Collapse
|
|
45
|
Germination results in reduced allergenicity of peanut by degradation of allergens and resveratrol enrichment. INNOV FOOD SCI EMERG 2018. [DOI: 10.1016/j.ifset.2018.10.015] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
|
|
46
|
Zhang T, Shi Y, Zhao Y, Tang G, Niu B, Chen Q. Boiling and roasting treatment affecting the peanut allergenicity. ANNALS OF TRANSLATIONAL MEDICINE 2018; 6:357. [PMID: 30370284 DOI: 10.21037/atm.2018.05.08] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Background Peanut allergy appears to be less prevalent in other parts of the world than North America and several European countries, and it has been proposed difference in cooking practices may be responsible. In this study, the boiling and roasting processes were investigated to find a potential method to enhanced or reduce the allergenicity. Methods The allergenicity of different peanut products, as reflected by changes in ethology (diarrhea and weight loss) and pathology (splenomegaly and jejunum breakage) were observed, and relevant serological indexes were determined after feeding different peanut products. Different peanut proteins were used to analyze the ability to resistance digestion in simulated gastric fluid (SGF). Ultraviolet spectrum and CD spectra were used to analyze structure changes of Ara h 2 in roasting and boiling treatment. Results In the detection of the corresponding serological indicators, boiled peanuts show a lower sensitization than roasted and raw peanuts. SGF experiments demonstrated an increased resistance of roasted peanut protein to digestion. The results of ultraviolet spectrum and CD spectra showed that the roasting and boiling causes altered structures of the Ara h 2 peanut allergens. Conclusions The summary show that different thermal processing may affect the structure and immunoreactivity, and the sensitization of roasted or boiled peanuts will be enhanced or reduced.
Collapse
Affiliation(s)
- Tong Zhang
- Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Yunfeng Shi
- Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Yanqing Zhao
- Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Guowei Tang
- Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Bing Niu
- Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Qin Chen
- Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai 200444, China
| |
Collapse
|
|
47
|
Yin HY, Fang TJ, Li YT, Fung YF, Tsai WC, Dai HY, Wen HW. Rapidly detecting major peanut allergen-Ara h2 in edible oils using a new immunomagnetic nanoparticle-based lateral flow assay. Food Chem 2018; 271:505-515. [PMID: 30236709 DOI: 10.1016/j.foodchem.2018.07.064] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Revised: 06/12/2018] [Accepted: 07/11/2018] [Indexed: 12/20/2022]
Abstract
Ara h2 is a major peanut allergen that induces rashes, vomiting, diarrhea, and anaphylactic shock. Since peanut is a major source in producing edible oils globally, Ara h2 residues can be present in various edible oils. In this work, an immunomagnetic nanoparticle-based lateral flow assay for identifying Ara h2 in edible oils is developed. This assay exhibits high sensitivity with a visual detection limit of 0.1 mg/kg Ara h2 in oil, and favorable specificity in differentiating peanut from seeds and nuts. The calculated CV values of intra- and inter-assay were 6.73-10.21% and 4.75-8.57%, respectively, indicating high reproducibility. In an analysis of 26 oil products, Ara h2 was detected in two peanut oils as 0.122 ± 0.026 mg/kg and 0.247 ± 0.027 mg/kg. The entire method takes 5 h, including a 3.5-h sample preparation. Hence, this method has the potential to be an effective way to screen edible oils for Ara h2.
Collapse
Affiliation(s)
- Hsin-Yi Yin
- Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan, ROC
| | - Tony J Fang
- Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan, ROC; Food Industry Research and Development Institute, Hsinchu, Taiwan, ROC.
| | - Yi-Ting Li
- Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan, ROC
| | - Yang-Fan Fung
- Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan, ROC
| | - Wen-Che Tsai
- Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan, ROC
| | - Hong-Yu Dai
- Crop Science Division and Guansi Experiment Station, Taiwan Agricultural Research Institute, Council of Agriculture, Executive Yuan, Taichung, Taiwan, ROC.
| | - Hsiao-Wei Wen
- Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan, ROC.
| |
Collapse
|
|
48
|
Abstract
Peanut allergens have the potential to negatively impact on the health and quality of life of millions of consumers worldwide. The seeds of the peanut plant Arachis hypogaea contain an array of allergens that are able to induce the production of specific IgE antibodies in predisposed individuals. A lot of effort has been focused on obtaining the sequences and structures of these allergens due to the high health risk they represent. At present, 16 proteins present in peanuts are officially recognized as allergens. Research has also focused on their in-depth immunological characterization as well as on the design of modified hypoallergenic derivatives for potential use in clinical studies and the formulation of strategies for immunotherapy. Detailed research protocols are available for the purification of natural allergens as well as their recombinant production in bacterial, yeast, insect, and algal cells. Purified allergen molecules are now routinely used in diagnostic multiplex protein arrays for the detection of the presence of allergen-specific IgE. This review gives an overview on the wealth of knowledge that is available on individual peanut allergens.
Collapse
Affiliation(s)
- Chiara Palladino
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Heimo Breiteneder
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
| |
Collapse
|
|
49
|
Khedri M, Ramezani M, Rafatpanah H, Abnous K. Detection of food-born allergens with aptamer-based biosensors. Trends Analyt Chem 2018. [DOI: 10.1016/j.trac.2018.04.001] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
|
|
50
|
Aguilera-Insunza R, Venegas LF, Iruretagoyena M, Rojas L, Borzutzky A. Role of dendritic cells in peanut allergy. Expert Rev Clin Immunol 2018; 14:367-378. [PMID: 29681186 DOI: 10.1080/1744666x.2018.1467757] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION The prevalence of peanut allergy (PA) has increased, affecting approximately 1.1% of children in Western countries. PA causes life-threatening anaphylaxis and frequently persists for life. There are no standardized curative therapies for PA, and avoidance of peanuts remains the main therapeutic option. A better understanding of the pathogenesis of PA is essential to identify new treatment strategies. Intestinal dendritic cells (DCs) are essential in the induction and maintenance of food tolerance because they present dietary allergens to T cells, thereby directing subsequent immune responses. Areas covered: In this review, we discuss the factors related to the acquisition of oral tolerance to peanut proteins. We focus on intestinal DC-related aspects, including the latest advances in the biology of intestinal DC subtypes, effect of tolerance-inducing factors on DCs, effect of dietary components on oral tolerance, and role of DCs in peanut sensitization. Expert commentary: Given the increasing prevalence of PA, difficulty of avoiding peanut products, and the potentially serious accidental reactions, the development of novel therapies for PA is needed. The ability of DCs to trigger tolerance or immunity makes them an interesting target for new treatment strategies against PA.
Collapse
Affiliation(s)
- Raquel Aguilera-Insunza
- a Department of Immunology and Rheumatology, School of Medicine , Pontificia Universidad Católica de Chile , Santiago , Chile
| | - Luis F Venegas
- b Translational Allergy and Immunology Laboratory, Department of Pediatric Infectious Diseases and Immunology , School of Medicine, Pontificia Universidad Católica de Chile , Santiago , Chile
| | - Mirentxu Iruretagoyena
- a Department of Immunology and Rheumatology, School of Medicine , Pontificia Universidad Católica de Chile , Santiago , Chile
| | - Leticia Rojas
- b Translational Allergy and Immunology Laboratory, Department of Pediatric Infectious Diseases and Immunology , School of Medicine, Pontificia Universidad Católica de Chile , Santiago , Chile
| | - Arturo Borzutzky
- b Translational Allergy and Immunology Laboratory, Department of Pediatric Infectious Diseases and Immunology , School of Medicine, Pontificia Universidad Católica de Chile , Santiago , Chile.,c Millennium Institute on Immunology and Immunotherapy, School of Medicine , Pontificia Universidad Católica de Chile , Santiago , Chile
| |
Collapse
|