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Nature Reviews. Immunology May 2023Allergen immunotherapy is a form of therapeutic vaccination for established IgE-mediated hypersensitivity to common allergen sources such as pollens, house dust mites... (Review)
Review
Allergen immunotherapy is a form of therapeutic vaccination for established IgE-mediated hypersensitivity to common allergen sources such as pollens, house dust mites and the venom of stinging insects. The classical protocol, introduced in 1911, involves repeated subcutaneous injection of increasing amounts of allergen extract, followed by maintenance injections over a period of 3 years, achieving a form of allergen-specific tolerance that provides clinical benefit for years after its discontinuation. More recently, administration through the sublingual route has emerged as an effective, safe alternative. Oral immunotherapy for peanut allergy induces effective 'desensitization' but not long-term tolerance. Research and clinical trials over the past few decades have elucidated the mechanisms underlying immunotherapy-induced tolerance, involving a reduction of allergen-specific T helper 2 (T2) cells, an induction of regulatory T and B cells, and production of IgG and IgA 'blocking' antibodies. To better harness these mechanisms, novel strategies are being explored to achieve safer, effective, more convenient regimens and more durable long-term tolerance; these include alternative routes for current immunotherapy approaches, novel adjuvants, use of recombinant allergens (including hypoallergenic variants) and combination of allergens with immune modifiers or monoclonal antibodies targeting the T2 cell pathway.
Topics: Humans; Hypersensitivity; Desensitization, Immunologic; Allergens; Administration, Sublingual; B-Lymphocytes
PubMed: 36253555
DOI: 10.1038/s41577-022-00786-1 -
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 -
The Journal of Allergy and Clinical... May 2023Allergenic cross-reactivity among food allergens complicates the diagnosis and management of food allergy. This can result in many patients being sensitized (having... (Review)
Review
Allergenic cross-reactivity among food allergens complicates the diagnosis and management of food allergy. This can result in many patients being sensitized (having allergen-specific IgE) to foods without exhibiting clinical reactivity. Some food groups such as shellfish, fish, tree nuts, and peanuts have very high rates of cross-reactivity. In contrast, relatively low rates are noted for grains and milk, whereas many other food families have variable rates of cross-reactivity or are not well studied. Although classical cross-reactive carbohydrate determinants are clinically not relevant, α-Gal in red meat through tick bites can lead to severe reactions. Multiple sensitizations to tree nuts complicate the diagnosis and management of patients allergic to peanut and tree nut. This review discusses cross-reactive allergens and cross-reactive carbohydrate determinants in the major food groups, and where available, describes their B-cell and T-cell epitopes. The clinical relevance of these cross-reactive B-cell and T-cell epitopes is highlighted and their possible impact on allergen-specific immunotherapy for food allergy is discussed.
Topics: Animals; Epitopes, T-Lymphocyte; Food Hypersensitivity; Nuts; Allergens; Immunoglobulin E; Cross Reactions
PubMed: 36932025
DOI: 10.1016/j.jaci.2022.12.827 -
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 -
The European Respiratory Journal Sep 2015Environmental allergens are an important cause of asthma and can contribute to loss of asthma control and exacerbations. Allergen inhalation challenge has been a useful... (Comparative Study)
Comparative Study Review
Environmental allergens are an important cause of asthma and can contribute to loss of asthma control and exacerbations. Allergen inhalation challenge has been a useful clinical model to examine the mechanisms of allergen-induced airway responses and inflammation. Allergen bronchoconstrictor responses are the early response, which reaches a maximum within 30 min and resolves by 1-3 h, and late responses, when bronchoconstriction recurs after 3-4 h and reaches a maximum over 6-12 h. Late responses are followed by an increase in airway hyperresponsiveness. These responses occur when IgE on mast cells is cross-linked by an allergen, causing degranulation and the release of histamine, neutral proteases and chemotactic factors, and the production of newly formed mediators, such as cysteinyl leukotrienes and prostaglandin D2. Allergen-induced airway inflammation consists of an increase in airway eosinophils, basophils and, less consistently, neutrophils. These responses are mediated by the trafficking and activation of myeloid dendritic cells into the airways, probably as a result of the release of epithelial cell-derived thymic stromal lymphopoietin, and the release of pro-inflammatory cytokines from type 2 helper T-cells. Allergen inhalation challenge has also been a widely used model to study potential new therapies for asthma and has an excellent negative predictive value for this purpose.
Topics: Allergens; Animals; Asthma; Bronchial Provocation Tests; Environmental Exposure; Female; Humans; Male; Prognosis; Respiratory Hypersensitivity; Risk Assessment
PubMed: 26206871
DOI: 10.1183/13993003.00536-2015 -
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 -
Current Opinion in Allergy and Clinical... Feb 2021Allergen-specific immunotherapy (AIT) is a highly economic, effective and disease-modifying form of allergy treatment but requires accurate prescription and monitoring.... (Review)
Review
PURPOSE OF REVIEW
Allergen-specific immunotherapy (AIT) is a highly economic, effective and disease-modifying form of allergy treatment but requires accurate prescription and monitoring. New molecular approaches are currently under development to improve AIT by reducing treatment-related side effects, cumbersome protocols and patients' compliance. We review the current advances regarding refined diagnosis for prescription and monitoring of AIT and the development of novel molecular vaccines for AIT. Finally, we discuss prophylactic application of AIT.
RECENT FINDINGS
There is evidence that molecular allergy diagnosis not only assists in the prescription and monitoring of AIT but also allows a refined selection of patients to increase the likelihood of treatment success. New data regarding the effects of AIT treatment with traditional allergen extracts by alternative routes have become available. Experimental approaches for AIT, such as virus-like particles and cell-based treatments have been described. New results from clinical trials performed with recombinant hypoallergens and passive immunization with allergen-specific antibodies highlight the importance of allergen-specific IgG antibodies for the effect of AIT and indicate opportunities for preventive allergen-specific vaccination.
SUMMARY
Molecular allergy diagnosis is useful for the prescription and monitoring of AIT and may improve the success of AIT. Results with molecular allergy vaccines and by passive immunization with allergen-specific IgG antibodies indicate the importance of allergen-specific IgG capable of blocking allergen recognition by IgE and IgE-mediated allergic inflammation as important mechanism for the success of AIT. New molecular vaccines may pave the road towards prophylactic allergen-specific vaccination.
Topics: Allergens; Desensitization, Immunologic; Dose-Response Relationship, Immunologic; Humans; Hypersensitivity; Immunogenicity, Vaccine; Seasons; Secondary Prevention; Treatment Outcome; Vaccination; Vaccines, Synthetic
PubMed: 33369572
DOI: 10.1097/ACI.0000000000000706 -
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