Studies of mitochondrial and nuclear DNA released from food allergen‐activated neutrophils. Implications for non‐IgE food allergy

2021 ◽  
Vol 42 (3) ◽  
pp. e59-e70
Author(s):  
Brigitte König ◽  
Anja N. Koch ◽  
Joseph A. Bellanti
Keyword(s):  
Mitochondrial Dna ◽  
Food Allergy ◽  
Calcium Binding ◽  
Inflammatory Responses ◽  
Immunoglobulin E ◽  
Innate Immune ◽  
Extracellular Dna ◽  
Test Results ◽  
Food Antigens ◽  
Ige Mediated

Background: Although adverse food reactions are commonly divided into immunoglobulin E (IgE) mediated food allergy (FA), and non-IgE FA, the current literature is providing support for the role of innate immune responses as an important component of non-IgE FA. Using a commercially available leukocyte activation (LA) assay, a recent quantitative study of total extracellular DNA released in cellular supernatants of human peripheral blood mononuclear cells exposed either to positive or negative tested foods demonstrated that leukocytes exposed to foods with positive LA test results showed higher DNA content than those exposed to foods with negative LA test results. In humans, the origin of DNA might be either the nucleus or the mitochondria. Analysis of emerging data from several laboratories, including our own, suggests that mitochondrial DNA induces inflammatory responses through induction of proinflammatory cytokines. Objective: This pilot study was designed primarily to convey the finding, and relevance of, mitochondrial DNA in the form of neutrophil extracellular traps (NET) as a new pathogenetic mechanism for innate immune-mediated non-IgE FA. Methods: The study population consisted of a total of six subjects, four in a major FA study group and two in a subgroup. Neutrophils were isolated and treated with food antigens that elicited positive and negative LA responses, and the released free DNA was analyzed for the cellular site of origin by using real-time polymerase chain reaction and for leukocyte calprotectin and S100 calcium-binding protein A12 (S100A12) proteins as markers of NETs. Results: We showed that cellular supernatants from neutrophils treated with foods that elicit positive LA responses can contain increased DNA levels of nuclear as well as mitochondrial origin. Supernatants from neutrophils treated with negative tested food (LA) responses did not induce the release of nuclear or mitochondrial DNA. Conclusion: Analysis of our data suggested that the induction of NETs that contain proinflammatory mitochondrial DNA may provide the critical link necessary for a better understanding of the pathogenesis of non‐IgE-mediated FA. These discoveries may not only facilitate better diagnostic tests of FA but should also improve clinical management of allergic and other inflammatory diseases.

scholarly journals Food allergy and breast-feeding

2020 ◽  
Vol 2 (1) ◽  
pp. 99-103
Author(s):  
Jennifer Pier ◽  
Kirsi M. Järvinen
Keyword(s):  
Food Allergy ◽  
Breast Feeding ◽  
Immunoglobulin E ◽  
Gastrointestinal Symptoms ◽  
Allergic Reactions ◽  
Unique Challenge ◽  
Food Avoidance ◽  
Food Antigens ◽  
Ige Mediated ◽  
Breast Fed

Breast-feeding is currently recommended as the optimal source of nutrition for infants; however, it is known that some individuals can excrete enough food antigens in breast milk to result in allergic reactions in infants, especially those already highly sensitized. These reactions can include non‐immunoglobulin E (IgE) mediated reactions, such as atopic dermatitis or gastrointestinal symptoms, and IgE-mediated reactions, such as anaphylaxis, although rare. Food reactions in infants who are breast-fed is a unique challenge because identifying the culprit foods may be more difficult and special consideration must be taken in ensuring proper nutrition during periods of food avoidance for both the infant and mother. This article reviews what is currently known about food allergy in infants who are breast-fed as well as offers insights into a proposed evaluation.

scholarly journals Antigen-Presenting Cells in Food Tolerance and Allergy

2021 ◽  
Vol 11 ◽  
Author(s):  
Elise G. Liu ◽  
Xiangyun Yin ◽  
Anush Swaminathan ◽  
Stephanie C. Eisenbarth
Keyword(s):  
Food Allergy ◽  
T Cell ◽  
Oral Tolerance ◽  
Immunoglobulin E ◽  
Antigen Presenting Cells ◽  
Western World ◽  
Dominant Form ◽  
Food Antigens ◽  
Different Types ◽  
Antigen Presenting

Food allergy now affects 6%–8% of children in the Western world; despite this, we understand little about why certain people become sensitized to food allergens. The dominant form of food allergy is mediated by food-specific immunoglobulin E (IgE) antibodies, which can cause a variety of symptoms, including life-threatening anaphylaxis. A central step in this immune response to food antigens that differentiates tolerance from allergy is the initial priming of T cells by antigen-presenting cells (APCs), primarily different types of dendritic cells (DCs). DCs, along with monocyte and macrophage populations, dictate oral tolerance versus allergy by shaping the T cell and subsequent B cell antibody response. A growing body of literature has shed light on the conditions under which antigen presentation occurs and how different types of T cell responses are induced by different APCs. We will review APC subsets in the gut and discuss mechanisms of APC-induced oral tolerance versus allergy to food identified using mouse models and patient samples.

scholarly journals Additives and preservatives: Role in food allergy

2020 ◽  
Vol 2 (1) ◽  
pp. 119-123
Author(s):  
Amber N. Pepper ◽  
Panida Sriaroon ◽  
Mark C. Glaum
Keyword(s):  
Food Allergy ◽  
Immunoglobulin E ◽  
Skin Prick Testing ◽  
Food Additives ◽  
Specific Ige ◽  
Food Additive ◽  
Blood Testing ◽  
Commercial Products ◽  
Natural Substances ◽  
Ige Mediated

Food additives are natural or synthetic substances added to foods at any stage of production to enhance flavor, texture, appearance, preservation, safety, or other qualities. Common categories include preservatives and antimicrobials, colorings and dyes, flavorings, antioxidants, stabilizers, and emulsifiers. Natural substances rather than synthetics are more likely to cause hypersensitivity. Although rare, food additive hypersensitivity should be suspected in patients with immunoglobulin E (IgE)-mediated reactions to multiple, unrelated foods, especially if the foods are prepared outside of the home or when using commercial products. A complete and thorough history is vital. Skin prick testing and/or specific IgE blood testing to food additives, if available, additive avoidance diets, and blind oral challenges can help establish the diagnosis. Once an allergy to a food additive is confirmed, management involves avoidance and, if necessary, carrying self-injectable epinephrine.

scholarly journals Mechanisms Underlying the Skin-Gut Cross Talk in the Development of IgE-Mediated Food Allergy

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3830
Author(s):  
Marloes van Splunter ◽  
Liu Liu ◽  
R.J. Joost van Neerven ◽  
Harry J. Wichers ◽  
Kasper A. Hettinga ◽  
...  
Keyword(s):  
Food Allergy ◽  
Gastrointestinal Tract ◽  
Immune Tolerance ◽  
Allergic Sensitization ◽  
Therapeutic Strategies ◽  
Dietary Proteins ◽  
Oral Ingestion ◽  
Food Antigens ◽  
Ige Mediated ◽  
Gastrointestinal Inflammation

Immune-globulin E (IgE)-mediated food allergy is characterized by a variety of clinical entities within the gastrointestinal tract, skin and lungs, and systemically as anaphylaxis. The default response to food antigens, which is antigen specific immune tolerance, requires exposure to the antigen and is already initiated during pregnancy. After birth, tolerance is mostly acquired in the gut after oral ingestion of dietary proteins, whilst exposure to these same proteins via the skin, especially when it is inflamed and has a disrupted barrier, can lead to allergic sensitization. The crosstalk between the skin and the gut, which is involved in the induction of food allergy, is still incompletely understood. In this review, we will focus on mechanisms underlying allergic sensitization (to food antigens) via the skin, leading to gastrointestinal inflammation, and the development of IgE-mediated food allergy. Better understanding of these processes will eventually help to develop new preventive and therapeutic strategies in children.

scholarly journals Using oral food challenges to provide clarity and confidence when diagnosing food allergies

2021 ◽  
Vol 3 (1) ◽  
pp. 3-7 ◽  
Author(s):  
Justin Greiwe
Keyword(s):  
Food Allergy ◽  
Immunoglobulin E ◽  
Food Challenge ◽  
Clinical History ◽  
The United States ◽  
Oral Immunotherapy ◽  
Food Allergies ◽  
Ige Mediated ◽  
Challenge Education ◽  
Food Challenges

A verified food allergy can be an impactful life event that leads to increased anxiety and measurable effects on quality of life. Allergists play a key role in framing this discussion and can help alleviate underlying fears by promoting confidence and clarifying safety concerns. Correctly diagnosing a patient with an immunoglobulin E (IgE) mediated food allergy remains a nuanced process fraught with the potential for error and confusion. This is especially true in situations in which the clinical history is not classic, and allergists rely too heavily on food allergy testing to provide a confirmatory diagnosis. A comprehensive medical history is critical in the diagnosis of food allergy and should be used to determine subsequent testing and interpretation of the results. Oral food challenge (OFC) is a critical procedure to identify patients with an IgE-mediated food allergy when the history and testing are not specific enough to confirm the diagnosis and can be a powerful teaching tool regardless of outcome. Although the safety and feasibility of performing OFC in a busy allergy office have always been a concern, in the hands of an experienced and trained provider, OFC is a safe and reliable procedure for patients of any age. With food allergy rates increasing and analysis of recent data that suggests that allergists across the United States are not providing this resource consistently to their patients, more emphasis needs to be placed on food challenge education and hands-on experience. The demand for OFCs will only continue to increase, especially with the growing popularity of oral immunotherapy programs; therefore, it is essential that allergists become familiar with the merits and limitations of current testing modalities and open their doors to using OFCs in the office.

scholarly journals Clinical manifestations of immunoglobulin E‐mediated food allergy, including pollen‐food allergy syndrome

2020 ◽  
Vol 2 (1) ◽  
pp. 22-25
Author(s):  
Pooja Varshney ◽  
Jacqueline A. Pongracic
Keyword(s):  
Food Allergy ◽  
Immunoglobulin E ◽  
Acute Infection ◽  
Clinical Manifestations ◽  
Gastrointestinal Symptoms ◽  
Physical Exertion ◽  
Allergic Reactions ◽  
Cutaneous Manifestations ◽  
Ige Mediated ◽  
Inflammatory Drugs

Immunoglobulin E-(IgE) mediated food allergy affects people of all ages but does not have a consistent presentation and may result in various manifestations, even for an individual. The onset of symptoms is usually quite rapid, minutes to a few hours after consumption of the allergen, although exceptions exist. Cutaneous and gastrointestinal symptoms are the most common clinical manifestations; however, they are not present in all allergic reactions. Clinicians, particularly those in emergency care settings, need to be aware that the lack of cutaneous manifestations does not exclude the possibility of anaphylaxis. It is extremely unusual for food allergy reactions to present with isolated upper or lower respiratory symptoms, nor is chronic urticaria a manifestation of food allergy. Clinical manifestations of IgE-mediated food allergy range from mild to severe and, in rare cases, can be fatal. Mild, localized reactions, such as those that occur in pollen‐food allergy syndrome, occur in individuals with sensitization to pollens. A small proportion of patients with this syndrome develop anaphylaxis. Alcohol, medications (nonsteroidal anti-inflammatory drugs, antacids), physical exertion, increased body temperature, acute infection, and menstruation are factors that are known to augment the severity of food-induced allergic reactions.

scholarly journals Updates on Food Allergy, Increasingly Prevalent Challenge

2018 ◽  
Vol 10 (3) ◽  
pp. 152
Author(s):  
Tonny Tanus ◽  
Sunny Wangko
Keyword(s):  
Atopic Dermatitis ◽  
Food Allergy ◽  
Eosinophilic Esophagitis ◽  
Immunoglobulin E ◽  
Pediatric Population ◽  
Food Allergies ◽  
Food Protein ◽  
Safety Issues ◽  
Ige Mediated ◽  
Allergic Disorders

Abstrak: Prevalensi alergi makanan makin meningkat di seluruh dunia dan mengenai semua usia. Keparahan dan kompleksitas penyakit juga meningkat terlebih pada populasi anak. Terdapat beberapa jenis reaksi alergi yang dibahas: immunoglobulin E (IgE) mediated allergies and anaphylaxis, food triggered atopic dermatitis, eosinophilic esophagitis, dan non IgE mediated gastrointestinal food allergic disorders seperti food protein induced enterocolitis syndrome (FPIEs). Tes alergi, baik melalui kulit maupun IgE yang telah dikerjakan sekian lama masih dibebani dengan hasil positif palsu dan negatif palsu yang bermakna dengan manfaat terbatas pada beberapa alergi makanan. Selain menghindari, tidak terdapat terapi yang ampuh untuk alergi makanan. Berbagai imunoterapi telah dipelajari melalui jalur, subkutan, epikutan, oral dan sublingual yang hanya menghasilkan desensitisasi sementara dan dibebani dengan berbagai isu mengenai keamanannya. Agen biologik yang menghambat sitokin/interleukin (IL) dan molekul pada reaksi alergi makanan tampaknya merupakan pilihan yang menjanjikan. Anti IgE telah dipergunakan pada asma dan urtikaria kronis. Anti IL-4 dan IL-13 yang menghambat produksi IgE diindikasikan untuk dermatitis atopik. Anti eosinofil anti IL-5 berhasil menurunkan eksaserbasi asma. Berbagai agen biologik telah dipelajari untuk berbagai kondisi alergik dan imunologik, tetapi efektivitas dan kepraktisan terapi yang mahal ini untuk alergi makanan masih menjadi tanda tanya.Kata kunci: alergi makanan, reaksi alergi, terapi alergi makananAbstract: Food allergies have been increasing in prevalence for years affecting all ages. Disease severity and complexity have also increased, especially in the pediatric population. There are several types of reactions including: immunoglobulin-E (IgE) mediated allergies and anaphylaxis, food-triggered atopic dermatitis, eosinophilic esophagitis, and non IgE mediated gastrointestinal food allergic disorders such as FPIEs. Though allergy testing has been around for years, both skin and IgE testing are burdened by significant false positives and negatives, and are only useful in some food allergies. Avoidance is the sole therapy for food allergy. A variety of immunotherapies have been studied; subcutaneous, epicutaneous, oral, and sublingual. At best they only produce a temporary state of desensitization and have many safety issues. Examples of biologicals which block critical cytokines/interleukins (IL) in allergic conditions are Anti IgE, anti IL-4 and IL-13, and Anti eosinophils, Anti IL-5. Other biologicals are being studied for allergic conditions, but whether these expensive future treatments will be proven effective and practical in food allergy is unknown.Keywords: food allergy, allergic reaction, food allergy therapy

scholarly journals Immunoglobulin E (IgE)-Mediated Food Allergy in Children: Epidemiology, Pathogenesis, Diagnosis, Prevention, and Management

Medicina ◽  
2020 ◽  
Vol 56 (3) ◽  
pp. 111 ◽  
Author(s):  
Simona Barni ◽  
Giulia Liccioli ◽  
Lucrezia Sarti ◽  
Mattia Giovannini ◽  
Elio Novembre ◽  
...  
Keyword(s):  
Food Allergy ◽  
Immunoglobulin E ◽  
Public Health Problem ◽  
Elimination Diet ◽  
Food Allergies ◽  
Major Public Health Problem ◽  
Double Blind ◽  
Detailed Medical History ◽  
Ige Mediated

A food allergy is an immunoglobulin E (IgE)-mediated hypersensitive reaction to food, which consists in the appearance of allergic symptoms; it can vary from common urticaria to even fatal anaphylaxis. The prevalence of food allergies has been increasing in the past twenty years and it represents a major public health problem in industrialized countries. The mechanism that leads to food allergies is the lack of immunologic and clinical tolerance to food allergens. The diagnosis of IgE-mediated food allergies is based on the combined use of a detailed medical history, in-vivo, and in-vitro research of specific IgE, the elimination diet, and the double-blind placebo-controlled food challenge. The only currently available treatment for allergies is the strict elimination diet. This type of attitude, which we could define as “passive”, does not overcome the risk of accidental reactions due to involuntary intake of the culprit food. For food allergy management, an “active” approach is urgently needed, such as specific allergen immunotherapy, which is currently under development and only used for research purposes. This article aims to give an updated review of IgE-mediated food allergies in pediatric populations in terms of epidemiology, pathogenesis, prevention, diagnosis, and management.

scholarly journals Developing food allergy: a potential immunologic pathway linking skin barrier to gut

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2660 ◽  
Author(s):  
Yui-Hsi Wang
Keyword(s):  
Food Allergy ◽  
Mast Cells ◽  
Immunoglobulin E ◽  
Lymphoid Cells ◽  
Th2 Cells ◽  
Allergic Reactions ◽  
Mucosal Mast Cells ◽  
Life Threatening ◽  
Ige Mediated

Immunoglobulin E (IgE)-mediated food allergy is an adverse reaction to foods and is driven by uncontrolled type-2 immune responses. Current knowledge cannot explain why only some individuals among those with food allergy are prone to develop life-threatening anaphylaxis. It is increasingly evident that the immunologic mechanisms involved in developing IgE-mediated food allergy are far more complex than allergic sensitization. Clinical observations suggest that patients who develop severe allergic reactions to food are often sensitized through the skin in early infancy. Environmental insults trigger epidermal thymic stromal lymphopoietin and interleukin-33 (IL-33) production, which endows dendritic cells with the ability to induce CD4+TH2 cell-mediated allergic inflammation. Intestinal IL-25 propagates the allergic immune response by enhancing collaborative interactions between resident type-2 innate lymphoid cells and CD4+TH2 cells expanded by ingested antigens in the gastrointestinal tract. IL-4 signaling provided by CD4+TH2 cells induces emigrated mast cell progenitors to become multi-functional IL-9-producing mucosal mast cells, which then expand greatly after repeated food ingestions. Inflammatory cytokine IL-33 promotes the function and maturation of IL-9-producing mucosal mast cells, which amplify intestinal mastocytosis, resulting in increased clinical reactivity to ingested food allergens. These findings provide the plausible view that the combinatorial signals from atopic status, dietary allergen ingestions, and inflammatory cues may govern the perpetuation of allergic reactions from the skin to the gut and promote susceptibility to life-threatening anaphylaxis. Future in-depth studies of the molecular and cellular factors composing these stepwise pathways may facilitate the discovery of biomarkers and therapeutic targets for diagnosing, preventing, and treating food allergy.

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