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EBioMedicine Jul 2023One of the important adverse impacts of climate change on human health is increases in allergic respiratory diseases such as allergic rhinitis and asthma. This impact is... (Review)
Review
One of the important adverse impacts of climate change on human health is increases in allergic respiratory diseases such as allergic rhinitis and asthma. This impact is via the effects of increases in atmospheric carbon dioxide concentration and air temperature on sources of airborne allergens such as pollen and fungal spores. This review describes these effects and then explores three translational mitigation approaches that may lead to improved health outcomes, with recent examples and developments highlighted. Impacts have already been observed on the seasonality, production and atmospheric concentration, allergenicity, and geographic distribution of airborne allergens, and these are projected to continue into the future. A technological revolution is underway that has the potential to advance patient management by better avoiding associated increased exposures, including automated real-time airborne allergen monitoring, airborne allergen forecasting and modelling, and smartphone apps for mitigating the health impacts of airborne allergens.
Topics: Humans; Climate Change; Allergens; Pollen; Asthma
PubMed: 36805358
DOI: 10.1016/j.ebiom.2023.104478 -
European Annals of Allergy and Clinical... Nov 2020Specific immunotherapy is the only treatment acting on the causes and not only on symptoms of respiratory allergy. It was first introduced as subcutaneous immunotherapy... (Review)
Review
Specific immunotherapy is the only treatment acting on the causes and not only on symptoms of respiratory allergy. It was first introduced as subcutaneous immunotherapy (SCIT) with the aim to induce immunological tolerance to the administered allergen(s). In the 1980s, sublingual immunotherapy (SLIT) was developed, mainly to improve the safety, which was a critical issue at that time. This article reviewed the available literature, including a large number of randomized controlled trials, meta-analyses, and real-life studies as well, on the outcomes of SCIT and SLIT concerning the treatment critical issues of the two routes, that are efficacy, safety, cost-effectiveness, and compliance to treatment. The efficacy of SCIT and SLIT is similar in respiratory allergy, providing, based on the induction of typical changes in the immunologic response, an early control of symptoms that steadily increases during the treatment and its efficacy lasts after the recommended duration of three years. Such results are the reason why SCIT and SLIT have economic advantage over symptomatic drugs.
Topics: Administration, Sublingual; Allergens; Animals; Desensitization, Immunologic; Drug-Related Side Effects and Adverse Reactions; Humans; Hypersensitivity; Immune Tolerance; Injections, Subcutaneous; Respiratory Tract Diseases
PubMed: 32372588
DOI: 10.23822/EurAnnACI.1764-1489.150 -
Current Opinion in Allergy and Clinical... Dec 2014Allergen-specific immunotherapy is the only curative treatment for allergic diseases. In spite of the great progress in both vaccine development and the methods of... (Review)
Review
PURPOSE OF REVIEW
Allergen-specific immunotherapy is the only curative treatment for allergic diseases. In spite of the great progress in both vaccine development and the methods of allergen immunotherapy (AIT) in recent years, several key problems related to limited efficacy, side-effects, low patient adherence and the relatively high costs due to the long duration (3-5 years) remain to be solved. The current approaches aiming at optimization of AIT are reviewed, including both conceptual studies in experimental models and proof-of-concept - as well as large, multicenter clinical studies.
RECENT FINDINGS
The most promising approaches to improve efficacy and safety of vaccine-based AIT include bypassing IgE binding and targeting allergen-specific T cells using hypoallergenic recombinant allergen derivatives and immunogenic peptides, the use of new adjuvants and stimulators of the innate immune response, the fusion of allergens to immune modifiers and peptide carrier proteins and new routes of vaccine administration.
SUMMARY
The cloning of allergen proteins and genetic engineering enabled the production of vaccines that have well defined molecular, immunologic and biologic characteristics as well as modified molecular structure. These new compounds along with new immunization protocols can bring us closer to the ultimate goal of AIT, that is, complete cure of a large number of allergic patients.
Topics: Allergens; Clinical Trials as Topic; Drug Design; Humans; Hypersensitivity; Immunotherapy; Vaccines
PubMed: 25304230
DOI: 10.1097/ACI.0000000000000121 -
Immunologic Research Mar 2013Food allergy has become a major public health concern in westernized countries, and allergic reactions to peanuts are particularly common and severe. Allergens are... (Review)
Review
Food allergy has become a major public health concern in westernized countries, and allergic reactions to peanuts are particularly common and severe. Allergens are defined as antigens that elicit an IgE response, and most allergenic materials (e.g., pollens, danders, and foods) contain multiple allergenic proteins. This has led to the concept that there are "major" allergens and allergens of less importance. "Major allergens" have been defined as allergens that bind a large amount of IgE from the majority of patients and have biologic activity. However, the ability of an allergen to cross-link complexes of IgE and its high-affinity receptor FcεRI (IgE/FcεRI), which we have termed its allergic effector activity, does not correlate well with assays of IgE binding. To identify the proteins that are the most active allergens in peanuts, we and others have employed in vitro model assays of allergen-mediated cross-linking of IgE/FcεRI complexes and have demonstrated that the most potent allergens are not necessarily those that bind the most IgE. The importance of a specific allergen can be determined by measuring the allergic effector activity of that allergen following purification under non-denaturing conditions and by specifically removing the allergen from a complex allergenic extract either by chromatography or by specific immunodepletion. In our studies of peanut allergens, our laboratory has found that two related allergens, Ara h 2 and Ara h 6, together account for the majority of the effector activity in a crude peanut extract. Furthermore, murine studies demonstrated that Ara h 2 and Ara h 6 are not only the major elicitors of anaphylaxis in this system, but also can effectively desensitize peanut-allergic mice. As a result of these observations, we propose that the definition of a major allergen should be based on the potency of that allergen in assays of allergic effector activity and demonstration that removal of that allergen from an extract results in loss of potency. Using these criteria, Ara h 2 and Ara h 6 are the major peanut allergens.
Topics: Allergens; Animals; Antigens, Plant; Arachis; Humans; Immunoglobulin E; Peanut Hypersensitivity
PubMed: 22948807
DOI: 10.1007/s12026-012-8355-x -
Journal of Food Protection Jul 2020Preventing the transfer of allergens from one food to another via food contact surfaces in retail food environments is an important aspect of retail food safety....
ABSTRACT
Preventing the transfer of allergens from one food to another via food contact surfaces in retail food environments is an important aspect of retail food safety. Existing recommendations for wiping and cleaning food contact surfaces is mainly focused on preventing microorganisms, such as bacteria and viruses, from contaminating foods. The effectiveness of these wiping and cleaning recommendations for preventing the transfer of food allergens in retail and food service establishments remains unclear. This project investigated (i) allergen removal from surfaces by wiping with paper wipes, terry cloth, and alcohol quaternary ammonium chloride (quat) sanitizing wipes; (ii) cleaning of allergen-contaminated surfaces by using a wash-rinse-sanitize-air dry procedure; and (iii) allergen transfer from contaminated wipes to multiple surfaces. Food contact surfaces (stainless steel, textured plastic, and maple wood) were contaminated with peanut-, milk- and egg-containing foods and subjected to various wiping and cleaning procedures. For transfer experiments, dry paper wipes or wet cloths contaminated with allergenic foods were wiped on four surfaces of the same composition. Allergen-specific lateral flow devices were used to detect the presence of allergen residues on wiped or cleaned surfaces. Although dry wipes and cloths were not effective for removing allergenic foods, terry cloth presoaked in water or sanitizer solution, use of multiple quat wipes, and the wash-rinse-sanitize-air dry procedure were effective in allergen removal from surfaces. Allergens present on dry wipes were transferred to wiped surfaces. In contrast, minimal or no allergen transfer to surfaces was found when allergen-contaminated terry cloth was submerged in sanitizer solution prior to wiping surfaces. The full cleaning method (wash-rinse-sanitize-air dry) and soaking the terry cloth in sanitizer solution prior to wiping were effective at allergen removal and minimizing allergen transfer.
Topics: Allergens; Animals; Egg Hypersensitivity; Food Hypersensitivity; Food Services; Milk
PubMed: 32221544
DOI: 10.4315/JFP-20-025 -
Methods (San Diego, Calif.) Mar 2014The structure determination of major allergens is a prerequisite for analyzing surface exposed areas of the allergen and for mapping conformational epitopes. These may... (Review)
Review
The structure determination of major allergens is a prerequisite for analyzing surface exposed areas of the allergen and for mapping conformational epitopes. These may be determined by experimental methods including crystallographic and NMR-based approaches or predicted by computational methods. In this review we summarize the existing structural information on allergens and their classification in protein fold families. The currently available allergen-antibody complexes are described and the experimentally obtained epitopes compared. Furthermore we discuss established methods for linear and conformational epitope mapping, putting special emphasis on a recently developed approach, which uses the structural similarity of proteins in combination with the experimental cross-reactivity data for epitope prediction.
Topics: Allergens; Animals; Crystallography, X-Ray; Epitope Mapping; Epitopes; Humans; Hypersensitivity; Models, Molecular; Nuclear Magnetic Resonance, Biomolecular; Protein Structure, Secondary; Protein Structure, Tertiary; Recombinant Fusion Proteins; Software
PubMed: 23891546
DOI: 10.1016/j.ymeth.2013.07.024 -
International Archives of Allergy and... 2017The years 1988-1995 witnessed the beginning of allergen cloning and the generation of recombinant allergens, which opened up new avenues for the diagnosis and research... (Review)
Review
The years 1988-1995 witnessed the beginning of allergen cloning and the generation of recombinant allergens, which opened up new avenues for the diagnosis and research of human allergic diseases. Most crystal and solution structures of allergens have been obtained using recombinant allergens. Structural information on allergens allows insights into their evolutionary biology, illustrates clinically observed cross-reactivities, and makes the design of hypoallergenic derivatives for allergy vaccines possible. Recombinant allergens are widely used in molecule-based allergy diagnosis such as protein microarrays or suspension arrays. Recombinant technologies have been used to produce well-characterized, noncontaminated vaccine components with known biological activities including a variety of allergen derivatives with reduced IgE reactivity. Such recombinant hypoallergens as well as wild-type recombinant allergens have been used successfully in several immunotherapy trials for more than a decade to treat birch and grass pollen allergy. As a more recent application, the development of antibody repertoires directed against conformational epitopes during immunotherapy has been monitored by recombinant allergen chimeras. Although much progress has been made, the number and quality of recombinant allergens will undoubtedly increase and keep improving our knowledge in basic scientific investigations, diagnosis, and therapy of human allergic diseases.
Topics: Allergens; Animals; Desensitization, Immunologic; Humans; Hypersensitivity; Immunologic Tests; Molecular Structure; Recombinant Proteins; Vaccines
PubMed: 28467993
DOI: 10.1159/000464104 -
The Journal of Allergy and Clinical... May 2023Immunologic mechanism of action of allergoids remains poorly understood. Previous models of allergenicity and immunogenicity have yielded suboptimal knowledge of these...
BACKGROUND
Immunologic mechanism of action of allergoids remains poorly understood. Previous models of allergenicity and immunogenicity have yielded suboptimal knowledge of these immunotherapeutic vaccine products. Novel single-cell RNA sequencing technology offers a bridge to this gap in knowledge.
OBJECTIVE
We sought to identify the underpinning tolerogenic molecular and cellular mechanisms of depigmented-polymerized Phleum pratense (Phl p) extract.
METHODS
The molecular mechanisms underlying native Phl p, depigmented Phl p (DPG-Phl p), and depigmented-polymerized (DPG-POL-Phl p) allergoid were investigated by single-cell RNA sequencing. Allergen-specific T2A, T follicular helper (Tfh), and IL-10 regulatory B cells were quantified by flow cytometry in peripheral blood mononuclear cells from 16 grass pollen-allergic and 8 nonatopic control subjects. The ability of Phl p, DPG-Phl p, and DPG-POL-Phl p to elicit FcεRI- and FcεRII-mediated IgE responses was measured by basophil activation test and IgE-facilitated allergen binding assay.
RESULTS
Analysis revealed that DPG-POL-Phl p downregulated genes associated with T2 signaling, induced functional regulatory T cells exhibiting immunosuppressive roles through CD52 and Siglec-10, modulated genes encoding immunoproteasome that dysregulate the processing and presentation of antigens to T cells and promoted a shift from IgE toward an IgA and IgG responses. In grass pollen-allergic subjects, DPG-POL-Phl p exhibited reduced capacity to elicit proliferation of T2A, IL-4 Tfh and IL-21 Tfh cells while being the most prominent at inducing IL-10CD19CD5 and IL-10CD19CD5CD38CD24 regulatory B-cell subsets compared to Phl p (all P < .05). Furthermore, DPG-POL-Phl p demonstrated a hypoallergenic profile through basophil activation and histamine release compared to Phl p (31.54-fold, P < .001).
CONCLUSIONS
Single-cell RNA sequencing provides an in-depth resolution of the mechanisms underlying the tolerogenic profile of DPG-POL-Phl p.
Topics: Humans; Allergens; Poaceae; Interleukin-10; Leukocytes, Mononuclear; Immunoglobulin E; Pollen; Hypersensitivity; Phleum; Allergoids; Plant Extracts; Sequence Analysis, RNA; Plant Proteins
PubMed: 36649758
DOI: 10.1016/j.jaci.2022.11.030 -
Annals of Allergy, Asthma & Immunology... Sep 2017To review the current knowledge regarding recombinant and purified allergens and allergen-derived peptides. (Review)
Review
OBJECTIVE
To review the current knowledge regarding recombinant and purified allergens and allergen-derived peptides.
DATA SOURCES
PubMed, homepages relevant to the topic, and the National Institutes of Health clinical trial database were searched.
STUDY SELECTIONS
The literature was screened for studies describing purified and recombinant allergens and allergen-derived peptides. Studies relevant to the topic were included in this review.
RESULTS
Advantages and drawbacks of pure and defined recombinant allergens and peptides over allergen extracts in the context of allergy research, diagnosis, and allergen immunotherapy are discussed. We describe how these molecules are manufactured, which products are currently available on the market, and what the regulative issues are. We furthermore provide an overview of clinical studies with vaccines based on recombinant allergens and synthetic peptides. The possibility of prophylactic vaccination based on recombinant fusion proteins consisting of viral carrier proteins and allergen-derived peptides without allergenic activity are also discussed.
CONCLUSION
During the last 25 years more than several hundred allergen sequences were determined, which led to a production of recombinant allergens that mimic biochemically and immunologically their natural counterparts. Especially in Europe, recombinant allergens are increasingly replacing allergen extracts in diagnosis of allergy. Despite many challenges, such as high cost of clinical trials and regulative issues, allergy vaccines based on recombinant allergens and peptides are being developed and will likely soon be available on the market.
Topics: Allergens; Animals; Humans; Hypersensitivity; Peptides; Recombinant Proteins
PubMed: 28890016
DOI: 10.1016/j.anai.2016.11.022 -
Frontiers in Bioscience (Elite Edition) Jan 2016Arylamines are widely used in food, drugs, and cosmetics as well as other industries. These chemicals are present ubiquitously in cigarette smoke, smoke emitted from... (Review)
Review
Arylamines are widely used in food, drugs, and cosmetics as well as other industries. These chemicals are present ubiquitously in cigarette smoke, smoke emitted from cooking fume hoods as well as are generated by diverse industries. Arylamines can be generated by cleavage of azo dyes by intestinal and skin microbiota. Some arylamines are used as drugs while others are constituents of human metabolism. Many of the arylamines are mutagenic and carcinogenic. They are generally recognized as the major cause of human bladder cancer, but arylamines can induce cancers of other organs in humans and animals. Some arylamines are allergenic, causing lupus like syndrome, or other maladies. In view of their unbiquitious nature and the diseases they cause, arylamines are probably the most important chemicals causing health problems.
Topics: Allergens; Amines; Carcinogens; Humans; Lupus Erythematosus, Systemic; Urinary Bladder Neoplasms
PubMed: 26709643
DOI: 10.2741/E748