Review

Authors: Umut C Kucuksezer, Cevdet Ozdemir, Lacin Cevhertas...

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

Review

Authors: Judith Pekar, Davide Ret, Eva Untersmayr...

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

Authors: D G Marsh, L Goodfriend, T P King...

This article presents a nomenclature system for allergens which has been officially recommended by the International Union of Immunological Societies (IUIS). The nomenclature is based on proposals of the IUIS Sub-Committee for Allergen Nomenclature and is applicable to highly purified, well-characterized allergens and to non-purified or partially purified allergenic extracts.

Topics: Allergens; Terminology as Topic

PubMed: 3492310
DOI: No ID Found

Review

Authors: Sara Haunstrup Næraa, Niels-Erik Harbo Schollert, Peter Nytofte Flader Skov...

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

Authors: Daria Trifonova, Mirela Curin, Ksenja Riabova...

More than 10% of the world's population suffers from an immunoglobulin E (IgE)-mediated allergy to cats which is accompanied mainly by respiratory symptoms such as rhinitis and asthma. Several cat allergen molecules have been identified, but their allergenic activity has not been investigated in depth. Purified cat allergen molecules (Fel d 1, Fel d 2, Fel d 3, Fel d 4, Fel d 6, Fel d 7 and Fel d 8) were characterized via mass spectrometry and circular dichroism spectroscopy regarding their molecular mass and fold, respectively. Cat-allergen-specific IgE levels were quantified via ImmunoCAP measurements in IgE-sensitized subjects with (n = 37) and without (n = 20) respiratory symptoms related to cat exposure. The allergenic activity of the cat allergens was investigated by loading patients' IgE onto rat basophils expressing the human FcεRI receptor and studying the ability of different allergen concentrations to induce β-hexosaminidase release. Purified and folded cat allergens with correct masses were obtained. Cat-allergen-specific IgE levels were much higher in patients with a respiratory allergy than in patients without a respiratory allergy. Fel d 1, Fel d 2, Fel d 4 and Fel d 7 bound the highest levels of specific IgE and already-induced basophil degranulation at hundred-fold-lower concentrations than the other allergens. Fel d 1, Fel d 4 and Fel d 7 were recognized by more than 65% of patients with a respiratory allergy, whereas Fel d 2 was recognized by only 30%. Therefore, in addition to the major cat allergen Fel d 1, Fel d 4 and Fel d 7 should also be considered to be important allergens for the diagnosis and specific immunotherapy of cat allergy.

Topics: Humans; Rats; Animals; Allergens; Hypersensitivity; Immunoglobulin E; Basophils; Asthma

PubMed: 38069052
DOI: 10.3390/ijms242316729

Review

Authors: Sanny K Chan, Anna Pomés, Christiane Hilger...

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

Review

Authors: Maksymilian Chruszcz, Katarzyna Mikolajczak, Nicholas Mank...

BACKGROUND

Albumins are multifunctional proteins present in the blood serum of animals. They can bind and transport a wide variety of ligands which they accommodate due to their conformational flexibility. Serum albumins are highly conserved both in amino acid sequence and three-dimensional structure. Several mammalian and avian serum albumins (SAs) are also allergens. Sensitization to one of the SAs coupled with the high degree of conservation between SAs may result in cross-reactive antibodies in allergic individuals. Sensitivity to SA generally begins with exposure to an aeroallergen, which can then lead to cross-sensitization to serum albumins present in food.

SCOPE OF REVIEW

This review focuses on the allergenicity of SAs presented in a structural context.

MAJOR CONCLUSIONS

SA allergenicity is unusual taking into account the high sequence identity and similarity between SA from different species and human serum albumin. Cross-reactivity of human antibodies towards different SAs is one of the most important characteristics of these allergens.

GENERAL SIGNIFICANCE

Establishing a relationship between sequence and structure of different SAs and their interactions with antibodies is crucial for understanding the mechanisms of cross-sensitization of atopic individuals. Structural information can also lead to better design and production of recombinant SAs to replace natural proteins in allergy testing and desensitization. Therefore, structural analyses are important for diagnostic and treatment purposes. This article is part of a Special Issue entitled Serum Albumin.

Topics: Allergens; Amino Acid Sequence; Animals; Cross Reactions; Humans; Hypersensitivity; Models, Molecular; Molecular Sequence Data; Sequence Homology, Amino Acid; Serum Albumin

PubMed: 23811341
DOI: 10.1016/j.bbagen.2013.06.016

Authors: Beatriz Lara, Jesús Rojo, Ana R Costa...

Over one quarter of the population in industrialised countries suffers from some type of allergy and inhaled aeroallergens from pollen are the primary cause of allergic ailments. The networks for monitoring biological air quality measure the airborne pollen concentrations that characterize periods of exposure to major airborne aeroallergens but there are certain discrepancies in relation to the allergen-pollen dynamic. In this paper we analyse the airborne allergens Ole e 1, Phl p 1, Phl p 5 and Pla a 1, and interpreted the adjustments and mismatches in their concentrations in relation to airborne pollen. The influence of main environmental patterns was considered. The study was conducted in two urban areas of the centre and southwest of the Iberian Peninsula (Toledo in Spain and Évora in Portugal). Monitoring for pollen followed the standard protocol using Hirst volumetric spore traps and allergenic particles were quantified by ELISA assay. The results indicate that the discrepancies in this relationship were affected by the weather conditions up to 6 days prior. Precipitation and humidity above normal values caused a higher concentration of the allergen Pla a 1. This effect occurred in reverse in the case of humidity for the allergens Ole e 1 and Phl p 1. Humidity and precipitation generated the same pattern in the allergen-pollen relationship in both Phl p 1 and Phl p 5. Our findings show consistent results that allow to interpret the rate of discrepancy between allergen and pollen, and it can be used to improve allergy risk prediction models generated from atmospheric pollen.

Topics: Humans; Air Pollutants; Plant Proteins; Pollen; Allergens; Hypersensitivity

PubMed: 36280057
DOI: 10.1016/j.scitotenv.2022.159630

Review

Authors: Uta Jappe, Christian Schwager, Andra B Schromm...

Molecular allergology research has provided valuable information on the structure and function of single allergenic molecules. There are several allergens in food and inhalant allergen sources that are able to interact with lipid ligands different structural features: hydrophobic pockets, hydrophobic cavities, or specialized domains. For only a few of these allergens information on their associated ligands is already available. Several of the allergens are clinically relevant, so that it is highly probable that the individual structural features with which they interact with lipids have a direct effect on their allergenic potential, and thus on allergy development. There is some evidence for a protective effect of lipids delaying the enzymatic digestion of the peanut () allergen Ara h 8 (hydrophobic pocket), probably allowing this molecule to get to the intestinal immune system intact (sensitization). Oleosins from different food allergen sources are part of lipid storage organelles and potential marker allergens for the severity of the allergic reaction. House dust mite (HDM), is more often associated with allergic asthma than other sources of inhalant allergens. In particular, lipid-associated allergens from which are Der p 2, Der p 5, Der p 7, Der p 13, Der p 14, and Der p 21 have been reported to be associated with severe allergic reactions and respiratory symptoms such as asthma. The exact mechanism of interaction of these allergens with lipids still has to be elucidated. Apart from single allergens glycolipids have been shown to directly induce allergic inflammation. Several-in parts conflicting-data exist on the lipid (and allergen) and toll-like receptor interactions. For only few single allergens mechanistic studies were performed on their interaction with the air-liquid interface of the lungs, in particular with the surfactant components SP-A and SP-D. The increasing knowledge on protein-lipid-interaction for lipophilic and hydrophobic food and inhalant allergens on the basis of their particular structure, of their capacity to be integral part of membranes (like the oleosins), and their ability to interact with membranes, surfactant components, and transport lipids (like the lipid transfer proteins) are essential to eventually clarify allergy and asthma development.

Topics: Allergens; Animals; Antigens, Plant; Asthma; Carrier Proteins; Humans; Hypersensitivity; Lipid Metabolism; Lipids; Plant Proteins; Plants; Pulmonary Surfactant-Associated Protein A; Pulmonary Surfactant-Associated Protein D

PubMed: 30837983
DOI: 10.3389/fimmu.2019.00122

Review

Authors: Claudia Leoni, Mariateresa Volpicella, Maria Dileo...

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