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Allergology International : Official... Oct 2020Allergen-specific immunotherapy (AIT) is the mainstay treatment for the cure of allergic disorders, with depicted efficacy and safety by several trials and... (Review)
Review
Allergen-specific immunotherapy (AIT) is the mainstay treatment for the cure of allergic disorders, with depicted efficacy and safety by several trials and meta-analysis. AIT impressively contributes to the management of allergic rhinitis, asthma and venom allergies. Food allergy is a new arena for AIT with promising results, especially via novel administration routes. Cell subsets with regulatory capacities are induced during AIT. IL-10 and transforming growth factor (TGF)-β are the main suppressor cytokines, in addition to surface molecules such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1) within the micro milieu. Modified T- and B-cell responses and antibody isotypes, increased activity thresholds for eosinophils, basophils and mast cells and consequent limitation of inflammatory cascades altogether induce and maintain a state of sustained allergen-specific unresponsiveness. Established tolerance is reflected into the clinical perspectives as improvement of allergy symptoms together with reduced medication requirements and evolved disease severity. Long treatment durations, costs, reduced patient compliance and risk of severe, even life-threatening adverse reactions during treatment stand as major limiting factors for AIT. By development of purified non-allergenic, highly-immunogenic modified allergen extracts, and combinational usage of them with novel adjuvant molecules via new routes may shorten treatment durations and possibly reduce these drawbacks. AIT is the best model for custom-tailored therapy of allergic disorders. Better characterization of disease endotypes, definition of specific biomarkers for diagnosis and therapy follow-up, as well as precision medicine approaches may further contribute to success of AIT in management of allergic disorders.
Topics: Allergens; Animals; Desensitization, Immunologic; Humans; Hypersensitivity; Immune Tolerance; Inflammation
PubMed: 32900655
DOI: 10.1016/j.alit.2020.08.002 -
European Annals of Allergy and Clinical... Nov 2015Plant allergens, being one of the most widespread allergenic substances, are hard to avoid. Hence, their identification and characterization are of prime importance for... (Review)
Review
Plant allergens, being one of the most widespread allergenic substances, are hard to avoid. Hence, their identification and characterization are of prime importance for the diagnosis and treatment of food allergy. The reported allergies to fruits mainly evoke oral allergy syndrome caused by the presence of cross-reactive IgE to certain pollens and thus, allergy to fruits has also been linked to particular pollens. Many fruit allergies are being studied for their causative allergens, and are being characterized. Some tropical or exotic fruits are responsible for region-specific allergies for which only limited information is available, and generally lack allergen characterization. From a survey of the literature on fruit allergy, it is clear that some common fruits (apple, peach, musk melon, kiwi fruit, cherry, grape, strawberry, banana, custard apple, mango and pomegranate) and their allergens appear to be at the center of current research on food allergy. The present review focuses on common fruits reported as allergenic and their identified allergens; a brief description of allergens from six rare/tropical fruits is also covered.
Topics: Allergens; Antibody Specificity; Biomarkers; Cross Reactions; Food Hypersensitivity; Fruit; Humans; Immunoglobulin E; Plant Proteins, Dietary; Pollen; Predictive Value of Tests; Prognosis; Risk Factors; Skin Tests
PubMed: 26549334
DOI: No ID Found -
Frontiers in Immunology 2019Food anaphylaxis is on the increase, with those who have an allergy to peanuts, tree nuts, milk, and seafood at the highest risk of developing such a reaction. However,... (Review)
Review
Food anaphylaxis is on the increase, with those who have an allergy to peanuts, tree nuts, milk, and seafood at the highest risk of developing such a reaction. However, the diet in many societies is increasingly varied, much of the food consumed is prepared outside the home, and meals are often composed of many different ingredients. Anaphylaxis may occur to a composite food, and it may be unclear whether the reaction is due to contamination or to a culprit allergen present in an added ingredient. Composite foods can contain many allergic proteins present in small amounts, which do not always have to be labeled, unless they feature in European or US labeling regulations. These "hidden" allergens include mustard, celery, spices, lupine, pea, natural food colourings, and preservatives, but can occasionally include allergenic material from contaminants such as cereal mites. Hidden allergens can provoke severe reactions to seemingly unconnected foods which might then lead to a diagnosis of idiopathic anaphylaxis. The same problem can arise with two well-known types of food allergy; wheat-dependant exercise induced anaphylaxis and allergy to non-specific Lipid Transfer Protein allergens, both of which might only manifest when linked to a cofactor such as exercise. Many of these risk factors for food anaphylaxis have a common link; the public's engagement with popular concepts of health and fitness. This includes the development of a food and exercise culture involving the promotion and marketing of foods for their health-giving properties i.e., meat substitutes, wheat substitutes, supplements and alternative, or "natural" remedies for common ailments. Some of these foods have been reported as the cause of severe allergic reactions, but because they are often viewed as benign unlikely causes of severe allergic reactions, could be considered to be hidden allergens. The best resource to elicit the likelihood of a hidden allergen provoking an allergic reaction is to take a detailed history of the allergic reaction, presence of co-factors, foods suspected, type of food and where it was consumed. A good knowledge of commonly used ingredients, and list of potential hidden allergen suspects are essential tools for the food allergy detective.
Topics: Allergens; Anaphylaxis; Food Hypersensitivity; Humans
PubMed: 31001275
DOI: 10.3389/fimmu.2019.00673 -
Molecular Immunology Aug 2018For proteins to cause IgE-mediated allergic reactions, several common characteristics have to be defined, including small molecular size, solubility and stability to... (Review)
Review
For proteins to cause IgE-mediated allergic reactions, several common characteristics have to be defined, including small molecular size, solubility and stability to changing pH levels and enzymatic degradation. Nevertheless, these features are not unique for potent allergens, but are also observed in non-allergenic proteins. Due to the increasing awareness by regulatory authorities regarding the allergy pandemic, definition of characteristics unique to potent allergens would facilitate allergenicity assessment in the future. Despite major research efforts even to date the features unique for major allergens have not been elucidated so far. The route of allergen entry into the organism determines to a great extent these required characteristics. Especially orally ingested allergens are exposed to the harsh milieu of the gastrointestinal tract but might additionally be influenced by food processing. Depending on molecular properties such as disulphide bonds contributing to protein fold and formation of conformational IgE epitopes, posttranslational protein modification or protein food matrix interactions, enzymatic and thermal stability might differ between allergens. Moreover, also ligand binding influences structural stability. In the current review article, we aim at highlighting specific characteristics and molecular pattern contributing to a stabilized protein structure and overall allergenicity.
Topics: Allergens; Animals; Epitopes; Food Hypersensitivity; Humans; Immunoglobulin E; Proteins
PubMed: 29606336
DOI: 10.1016/j.molimm.2018.03.017 -
Frontiers in Immunology 2019The World Health Organization/International Union of Immunological Societies (WHO/IUIS) Allergen Nomenclature Sub-Committee was established in 1986 by leading allergists... (Review)
Review
The World Health Organization/International Union of Immunological Societies (WHO/IUIS) Allergen Nomenclature Sub-Committee was established in 1986 by leading allergists to standardize names given to proteins that cause IgE-mediated reactions in humans. The Sub-Committee's objective is to assign unique names to allergens based on a critical analysis of confidentially submitted biochemical and clinical data from researchers, often prior to publication to preserve consistency. The Sub-Committee maintains and revises the database as the understanding of allergens evolves. This report summarizes recent developments that led to updates in classification of cockroach group 1 and 5 allergens to animal as well as environmental and occupational allergens. Interestingly, routes, doses, and frequency of exposure often affects allergenicity as does the biochemical properties of the proteins and similarity to self and other proteins. Information required by the Sub-Committee now is more extensive than previously as technology has improved. Identification of new allergens requires identification of the amino acid sequence and physical characteristics of the protein as well as demonstration of IgE binding from subjects verified by described clinical histories, proof of the presence of the protein in relevant exposure substances, and demonstration of biological activity (skin prick tests, activation of basophils, or mast cells). Names are assigned based on taxonomy with the abbreviation of genus and species and assignment of a number, which reflects the priority of discovery, but more often now, the relationships with homologous proteins in related species.
Topics: Allergens; Animals; Humans; Terminology as Topic
PubMed: 31798576
DOI: 10.3389/fimmu.2019.02600 -
Molecules (Basel, Switzerland) May 2019Food allergies originate from adverse immune reactions to some food components. Ingestion of food allergens can cause effects of varying severity, from mild itching to... (Review)
Review
Food allergies originate from adverse immune reactions to some food components. Ingestion of food allergens can cause effects of varying severity, from mild itching to severe anaphylaxis reactions. Currently there are no clues to predict the allergenic potency of a molecule, nor are cures for food allergies available. Cutting-edge research on allergens is aimed at increasing information on their diffusion and understanding structure-allergenicity relationships. In this context, purified recombinant allergens are valuable tools for advances in the diagnostic and immunotherapeutic fields. Chitinases are a group of allergens often found in plant fruits, but also identified in edible insects. They are classified into different families and classes for which structural analyses and identification of epitopes have been only partially carried out. Moreover, also their presence in common allergen databases is not complete. In this review we provide a summary of the identified food allergenic chitinases, their main structural characteristics, and a clear division in the different classes.
Topics: Allergens; Animals; Chitinases; Cross Reactions; Epitope Mapping; Epitopes; Food Hypersensitivity; Humans; Immunoglobulin E; Insecta; Plant Proteins; Structure-Activity Relationship
PubMed: 31159327
DOI: 10.3390/molecules24112087 -
Allergy Dec 2020The continuous search for new allergens and the design of allergen derivatives improves the understanding of their allergenicity and aids the design of novel diagnostic... (Review)
Review
The continuous search for new allergens and the design of allergen derivatives improves the understanding of their allergenicity and aids the design of novel diagnostic and immunotherapy approaches. This article discusses the recent developments in allergen and epitope discovery, allergy diagnostics and immunotherapy. Structural information is crucial for the elucidation of cross-reactivity of marker allergens such as the walnut Jug r 6 or that of nonhomologous allergens, as shown for the peanut allergens Ara h 1 and 2. High-throughput sequencing, liposomal nanoallergen display, bead-based assays, and protein chimeras have been used in epitope discovery. The binding of natural ligands by the birch pollen allergen Bet v 1 or the mold allergen Alt a 1 increased the stability of these allergens, which is directly linked to their allergenicity. We also report recent findings on the use of component-resolved approaches, basophil activation test, and novel technologies for improvement of diagnostics. New strategies in allergen-specific immunotherapy have also emerged, such as the use of virus-like particles, biologics or novel adjuvants. The identification of dectin-1 as a key player in allergy to tropomyosins and the formyl peptide receptor 3 in allergy to lipocalins are outstanding examples of research into the mechanism of allergic sensitization.
Topics: Allergens; Antigens, Plant; Betula; Cross Reactions; Humans; Hypersensitivity; Immunoglobulin E; Plant Proteins; Pollen
PubMed: 32882057
DOI: 10.1111/all.14579 -
Dermatitis : Contact, Atopic,... 2020Identification of the etiological chemical agent(s) associated with a case(s) of allergic contact dermatitis (ACD) is important for both patient management and public... (Review)
Review
Identification of the etiological chemical agent(s) associated with a case(s) of allergic contact dermatitis (ACD) is important for both patient management and public health surveillance. Traditional patch testing can identify chemical allergens to which the patient is allergic. Confirmation of allergen presence in the causative ACD-associated material is presently dependent on labeling information, which may not list the allergenic chemical on the product label or safety data sheet. Dermatologists have expressed concern over the lack of laboratory support for chemical allergen identification and possibly quantification from patients' ACD-associated products. The aim of this review was to provide the clinician a primer to better understand the analytical chemistry of contact allergen confirmation and unknown identification, including types of analyses, required instrumentation, identification levels of confidence decision tree, limitations, and costs.
Topics: Allergens; Chemistry Techniques, Analytical; Chromatography, Gas; Chromatography, High Pressure Liquid; Chromatography, Paper; Chromatography, Thin Layer; Decision Trees; Dermatitis, Allergic Contact; Electrophoresis, Paper; Humans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Silica Gel
PubMed: 31433381
DOI: 10.1097/DER.0000000000000498 -
Ugeskrift For Laeger May 2018An emerging method for allergen-specific immunotherapy is intralymphatic placement, which only requires three injections with intervals of four weeks. In this review, we... (Review)
Review
An emerging method for allergen-specific immunotherapy is intralymphatic placement, which only requires three injections with intervals of four weeks. In this review, we summarise available evidence on clinical safety, biological efficacy and therapeutic outcomes. The treatment appears to be safe with only few and mild adverse reactions. The immunological activation profile is comparable to that known for subcutaneous therapy. Clinically, patients experienced fewer symptoms with less medication use with intralymphatic allergen-specific immunotherapy than with other types of immunotherapy. The number of studies is limited, and the studies have important limitations. More phase 3 studies are needed in order to make a conclusion.
Topics: Allergens; Desensitization, Immunologic; Humans; Injections, Intralymphatic; Rhinitis, Allergic; Treatment Outcome
PubMed: 29808813
DOI: No ID Found -
Frontiers in Immunology 2020The immune response to antigens is a key aspect of immunology, as it provides opportunities for therapeutic intervention. However, the induction of immunological... (Review)
Review
The immune response to antigens is a key aspect of immunology, as it provides opportunities for therapeutic intervention. However, the induction of immunological tolerance is an evolving area that is still not sufficiently understood. Allergen immunotherapy (AIT) is a disease-modulating therapy available for immunoglobulin E (IgE)-mediated airway diseases such as allergic rhinitis or allergic asthma. This disease-modifying effect is not only antigen driven but also antigen specific. The specificity and also the long-lasting, often life-long symptom reduction make the therapy attractive for patients. Additionally, the chance to prevent the onset of asthma by treating allergic rhinitis with AIT is important. The mechanism and, in consequence, therapy guiding biomarker are still in its infancy. Recent studies demonstrated that the interaction of T, B, dendritic, and epithelial cells and macrophages are individually contributing to clinical tolerance and therefore underline the need for a system to monitor the progress and success of AIT. As clinical improvement is often accompanied by decreases in numbers of effector cells in the tissue, analyses of cellular responses and cytokine pattern provide a good insight into the mechanisms of AIT. The suppression of type-2 immunity is accompanied by decreased levels of type-2 mediators such as epithelial CCL-26 and interleukin (IL)-4, IL-13 produced by T cells that are constituting the immune memory and are increasingly controlled by regulatory T and B cells following AIT. Immune tolerance is also associated with increased production of type-1 mediators like interferon-gamma, tissue-homeostating factors like indoleamine 2,3-dioxygenase (IDO) expressed by macrophages and dendritic cells. Although these individual genes were convincingly demonstrated to play a role immune tolerance, they do not predict therapy outcomes of AIT on an individual level. Therefore, combinations or ratios of gene expression levels are a promising way to achieve predictive value and definition of helpful biomarker.
Topics: Allergens; Biomarkers; Cytokines; Desensitization, Immunologic; Humans; Hypersensitivity; Immune Tolerance; Inflammation Mediators; Predictive Value of Tests; Treatment Outcome
PubMed: 32983092
DOI: 10.3389/fimmu.2020.01826