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Frontiers in Immunology 2018The study of autoimmunity mediated by immunoglobulin E (IgE) autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus... (Review)
Review
The study of autoimmunity mediated by immunoglobulin E (IgE) autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus erythematosus, bullous pemphigoid (BP), and chronic urticaria, both spontaneous and inducible, are most likely to be mediated, at least in part, by IgE autoantibodies. The situation in other conditions, such as autoimmune uveitis, rheumatoid arthritis, hyperthyroid Graves' disease, autoimmune pancreatitis, and even asthma, is far less clear but evidence for autoallergy is accumulating. To be certain of an autoallergic mechanism, it is necessary to identify both IgE autoantibodies and their targets as has been done with the transmembrane protein BP180 and the intracellular protein BP230 in BP and IL-24 in chronic spontaneous urticaria. Also, IgE-targeted therapies, such as anti-IgE, must have been shown to be of benefit to patients as has been done with both of these conditions. This comprehensive review of the literature on IgE-mediated autoallergy focuses on three related questions. What do we know about the prevalence of IgE autoantibodies and their targets in different diseases? What do we know about the relevance of IgE autoantibodies in different diseases? What do we know about the cellular and molecular effects of IgE autoantibodies? In addition to providing answers to these questions, based on a broad review of the literature, we outline the current gaps of knowledge in our understanding of IgE autoantibodies and describe approaches to address them.
Topics: Animals; Autoantibodies; Autoimmune Diseases; Autoimmunity; Humans; Immunoglobulin E
PubMed: 29686678
DOI: 10.3389/fimmu.2018.00689 -
Nature Microbiology Oct 2023Alterations in the gut microbiome, including diet-driven changes, are linked to the rising prevalence of food allergy. However, little is known about how specific gut...
Alterations in the gut microbiome, including diet-driven changes, are linked to the rising prevalence of food allergy. However, little is known about how specific gut bacteria trigger the breakdown of oral tolerance. Here we show that depriving specific-pathogen-free mice of dietary fibre leads to a gut microbiota signature with increases in the mucin-degrading bacterium Akkermansia muciniphila. This signature is associated with intestinal barrier dysfunction, increased expression of type 1 and 2 cytokines and IgE-coated commensals in the colon, which result in an exacerbated allergic reaction to food allergens, ovalbumin and peanut. To demonstrate the causal role of A. muciniphila, we employed a tractable synthetic human gut microbiota in gnotobiotic mice. The presence of A. muciniphila within the microbiota, combined with fibre deprivation, resulted in stronger anti-commensal IgE coating and innate type-2 immune responses, which worsened symptoms of food allergy. Our study provides important insights into how gut microbes can regulate immune pathways of food allergy in a diet-dependent manner.
Topics: Humans; Mice; Animals; Verrucomicrobia; Food Hypersensitivity; Akkermansia; Immunoglobulin E
PubMed: 37696941
DOI: 10.1038/s41564-023-01464-1 -
Nature Jun 2020Approximately one-third of the world's population suffers from allergies. Exposure to allergens crosslinks immunoglobulin E (IgE) antibodies that are bound to mast cells...
Approximately one-third of the world's population suffers from allergies. Exposure to allergens crosslinks immunoglobulin E (IgE) antibodies that are bound to mast cells and basophils, triggering the release of inflammatory mediators, including histamine. Although IgE is absolutely required for allergies, it is not understood why total and allergen-specific IgE concentrations do not reproducibly correlate with allergic disease. It is well-established that glycosylation of IgG dictates its effector function and has disease-specific patterns. However, whether IgE glycans differ in disease states or affect biological activity is completely unknown. Here we perform an unbiased examination of glycosylation patterns of total IgE from individuals with a peanut allergy and from non-atopic individuals without allergies. Our analysis reveals an increase in sialic acid content on total IgE from individuals with a peanut allergy compared with non-atopic individuals. Removal of sialic acid from IgE attenuates effector-cell degranulation and anaphylaxis in several functional models of allergic disease. Therapeutic interventions-including removing sialic acid from cell-bound IgE with a neuraminidase enzyme targeted towards the IgE receptor FcεRI, and administering asialylated IgE-markedly reduce anaphylaxis. Together, these results establish IgE glycosylation, and specifically sialylation, as an important regulator of allergic disease.
Topics: Adolescent; Adult; Aged; Allergens; Anaphylaxis; Animals; Case-Control Studies; Cell Degranulation; Child; Child, Preschool; Female; Glycosylation; Humans; Immunoglobulin E; Infant; Infant, Newborn; Male; Mice; Middle Aged; Models, Immunological; N-Acetylneuraminic Acid; Neuraminidase; Peanut Hypersensitivity; Receptors, IgE; Young Adult
PubMed: 32499653
DOI: 10.1038/s41586-020-2311-z -
Journal of Investigational Allergology... Dec 2023
Topics: Humans; Autoimmune Diseases; Liver; Immunoglobulin E
PubMed: 38095500
DOI: 10.18176/jiaci.0942 -
Deutsches Arzteblatt International Jul 2018Adverse drug reactions (ADRs) can be divided into pharmacological ADRs (type A) and hypersensitivity reactions (type B). Type B reactions can be further subdivided into... (Review)
Review
BACKGROUND
Adverse drug reactions (ADRs) can be divided into pharmacological ADRs (type A) and hypersensitivity reactions (type B). Type B reactions can be further subdivided into immediate (<1 h, urticaria, anaphylaxis) and delayed reactions (>1 h, variable manifestation like exanthema, hepatitis, cytopenias). Prevention of hypersensitivity is often still a challenge.
METHODS
Selective literature search in Medline and Google Scholar as well as research in ADR databases like OpenVigil or SIDER.
RESULTS
Laboratory tests ([specific] IgE, lymphocyte transformation test), histological examination, dermatological tests (prick tests, epicutaneous testing) and-under certain circumstances-provocation tests can be used for diagnostics. There are only a few pharmacogenetic biomarkers to predict hypersensitivity reactions. Currently, testing for defined HLA genes is mandatory before prescription of abacavir and before the use of carbamazepine in Han Chinese or Thai patients. Immediate discontinuation of the trigger is essential in all allergic hypersensitivity reactions. Immediate reactions are treated with antihistamines, glucocorticoids and occasionally with epinephrine. Delayed reactions are usually treated with glucocorticoids.
CONCLUSION
Careful, structured diagnostics in case of suspected hypersensitivity together with adequate documentation (allergy passport) is necessary in order to avoid incidents in patients receiving subsequent treatment. Consistent use of existing resources (diagnostics and documentation) can help to avoid hypersensitivity reactions or to rapidly recognize and treat them, respectively.
Topics: Biomarkers; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Humans; Immunoglobulin E; Skin Tests
PubMed: 30135011
DOI: 10.3238/arztebl.2018.0501 -
Nutrients Jun 2021Nutrition and intestinal function are strictly interrelated [...].
Nutrition and intestinal function are strictly interrelated [...].
Topics: Celiac Disease; Child; Child Nutritional Physiological Phenomena; Gastroenterology; Humans; Immunoglobulin E; Nutritional Status; Probiotics
PubMed: 34201080
DOI: 10.3390/nu13061965 -
Annals of Allergy, Asthma & Immunology... Mar 2016
Review
Topics: Animals; Humans; Hypersensitivity; Immunity; Immunoglobulin E; Receptors, IgE
PubMed: 26945494
DOI: 10.1016/j.anai.2015.10.026 -
Current Topics in Microbiology and... 2019IgE are absolutely required for initiation of allergy reactions, which affect over 20% of the world's population. IgE are the least prevalent immunoglobulins in... (Review)
Review
IgE are absolutely required for initiation of allergy reactions, which affect over 20% of the world's population. IgE are the least prevalent immunoglobulins in circulation with 12-h and 2-day half-lives in mouse and human serum, respectively, but an extended tissue half-life of 3-weeks bound to the surface of mast cells by the high affinity IgE receptor, FcεRI (Gould and Sutton 2008). Although the importance of glycosylation to IgG biology is well established, less is known regarding the contribution of IgE glycosylation to allergic inflammation. IgE has seven and nine N-linked glycosylation sites distributed across human and murine constant chains, respectively. Here we discuss studies that have analyzed IgE glycosylation and its function, and how IgE glycosylation contributions to health and disease.
Topics: Animals; Glycosylation; Health; Humans; Hypersensitivity; Immunoglobulin E; Mast Cells; Receptors, IgE
PubMed: 30820668
DOI: 10.1007/82_2019_151 -
The Journal of Allergy and Clinical... Jun 2016Progress in protein chemistry in the 1950s revealed that the biologic activities of proteins, such as hemoglobin and enzymes, are based on partial structures in the... (Review)
Review
Progress in protein chemistry in the 1950s revealed that the biologic activities of proteins, such as hemoglobin and enzymes, are based on partial structures in the protein molecules. This principle suggested to us the possibility that the human antibodies responsible for induction of reaginic hypersensitivity reactions might have unique structures that are lacking in the antibody molecules involved in immunity and that the differences in the structures of human antibody molecules can be recognized by the immune systems of experimental animals. Our studies were based on the hypothesis that reaginic antibody activity is associated with a unique immunoglobulin isotype, which is now called IgE. As expected, identification of IgE facilitated the analysis of immunologic mechanisms of reaginic hypersensitivity. Subsequent studies revealed that IgE specifically bound to basophilic granulocytes and mast cells through the Fc portion of the molecules and that cross-linking of the cell-bound IgE antibody molecules by allergen induced the release of bioactive mediators, such as histamine and leukotrienes, which initiate allergic reactions.
Topics: Allergy and Immunology; Animals; History, 20th Century; Humans; Hypersensitivity; Immunoglobulin E; Reagins
PubMed: 27090936
DOI: 10.1016/j.jaci.2015.12.1343 -
Postepy Higieny I Medycyny... May 2014Toxoplasmosis is a worldwide infection caused by the intracellular parasite Toxoplasma gondii. At least a third of the world human population is infected with the... (Review)
Review
Toxoplasmosis is a worldwide infection caused by the intracellular parasite Toxoplasma gondii. At least a third of the world human population is infected with the parasite, making it one of the most successful parasitic infections. Primary maternal infection may cause health-threatening sequelae for the fetus, or even cause death of the uterus. Reactivation of a latent infection in immune deficiency conditions such as AIDS and organ transplantation can cause fatal toxoplasmic encephalitis. Toxoplasmosis is a major cause of chorioretinitis, especially in individuals with impaired immune systems. In the acute phase, directly after invading the body, T. gondii begins to multiply rapidly. In the majority of cases acquired toxoplasmosis is asymptomatic. In the second week of infection, specific IgM antibodies are present in the blood. IgE antibodies appear at the same time, slightly preceding specific IgA antibodies. The concentration of IgE can be one of the parameters used for diagnosing an infection with T. gondii. Laboratory diagnosis, i.e. IgE and serologic assays, plays the main role in the diagnosis of congenital infection and assists in the confirmatory diagnosis of toxoplasmic encephalitis and ocular toxoplasmosis. This article is a review of IgE in toxoplasmosis.
Topics: Antibodies, Protozoan; Humans; Immunoglobulin E; Toxoplasma; Toxoplasmosis
PubMed: 24864110
DOI: 10.5604/17322693.1102581