Are the Terms Major and Minor Allergens Useful for Precision Allergology?

Caraballo, Luis; Valenta, Rudolf; Acevedo, Nathalie; Zakzuk, Josefina

doi:10.3389/fimmu.2021.651500

Cited by 40 publications

(50 citation statements)

References 25 publications

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“…clinical relevance which may be measured by determining its allergenic activity in vitro and in vivo needs to be taken into consideration as has been suggested recently (36,37). We expressed in Escherichia coli and purified recombinant Der p 7 and demonstrated that the molecule is folded by CD spectroscopy.…”

Section: Discussionmentioning

confidence: 95%

“…Der p 7 has been defined as a mid-tier house dust mite allergen recognized by more than 30% of HDM sensitized patients ( 3 ) but it has been shown that it can be a major HDM allergen recognized by more than 50% of HDM allergic patients in certain populations ( 5 , 9 ). However, not only the frequency of IgE recognition defines if an allergen is important but also its clinical relevance which may be measured by determining its allergenic activity in vitro and in vivo needs to be taken into consideration as has been suggested recently ( 36 , 37 ). We expressed in Escherichia coli and purified recombinant Der p 7 and demonstrated that the molecule is folded by CD spectroscopy.…”

Section: Discussionmentioning

confidence: 99%

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IgE Epitopes of the House Dust Mite Allergen Der p 7 Are Mainly Discontinuous and Conformational

et al. 2021

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BackgroundSeveral studies indicate that Der p 7 is an important and clinically relevant allergen of Dermatophagoides pteronyssinus which should be included in vaccines for treatment of house dust mite (HDM) allergy. Aim of this study was to characterize the IgE epitopes of Der p 7.MethodsRecombinant Der p 7 was expressed and purified, analyzed for fold by circular dichroism and tested for its allergenic activity by basophil activation. Seven overlapping, surface-exposed peptides (P1–P7) with a length of 27 to 37 amino acids, which spanned the Der p 7 sequence, were synthesized and tested for IgE reactivity and allergenic activity by basophil activation assay. Carrier-bound peptides were studied for their ability to induce allergen-specific IgG antibodies in rabbits. Peptide-specific antibodies were used to inhibit allergic patients` IgE binding to Der p 7 by ELISA for mapping of IgE epitopes.ResultsrDer p 7 showed high allergenic activity comparable with Der p 5, Der p 21, and Der p 23. None of the seven tested peptides showed any IgE reactivity or allergenic activity when tested with HDM- allergic patients indicating lack of sequential IgE epitopes on Der p 7. IgE inhibition experiments using anti-peptide specific IgGs and molecular modeling enabled us to identify discontinuous, conformational IgE epitopes of Der p 7.Conclusion and Clinical RelevanceIgE epitopes of Der p 7 belong to the conformational and discontinuous type whereas sequential Der p 7 peptides lack IgE reactivity. It should thus be possible to construct hypoallergenic vaccines for Der p 7 based on carrier-bound allergen peptides.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

IgE Epitopes of the House Dust Mite Allergen Der p 7 Are Mainly Discontinuous and Conformational

et al. 2021

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“…However, certain "allergens" may bind specifically IgE antibodies but do not induce cross-linking of effector cell-bound IgE and hence do not cause inflammatory reactions. A good example for such "IgE-reactive antigens" without allergenic activity are carbohydrate-containing determinants also termed CCDs which are present as cross-reactive moieties in a large number of unrelated allergen extracts and hence may give "false-positive" IgE test results meaning that for example a subject shows CCDspecific IgE reactivity but no allergic reaction upon contact with the allergen source (38,43,44). In contrast to IgE serology, SPT measures if an allergen extract can induce effector cell (i.e., mast cell, basophil) activation and thus informs if the sensitized subject may experience an allergic reaction to the tested extract.…”

Section: Frequencies Of Allergic Sensitizations To Allergen Sources In China: First Information From Allergen Extract-based Studiesmentioning

confidence: 99%

“…Quantitative measurements by ImmunoCAP or micro arrays eventually with basophil activation experiments performed with allergen molecules and not only prevalence data would be critical to determine the allergic load and thus the reagents needed for optimal immunotherapy. For optimal immunotherapy allergen molecules with clinical relevance as reflected by high IgE binding capacity and allergenic activity need to be identified (43).…”

Section: Information Regarding Molecular Sensitization Profiles In China Through First Studies Performed With Molecular Diagnosticsmentioning

confidence: 99%

The Molecular Allergen Recognition Profile in China as Basis for Allergen-Specific Immunotherapy

et al. 2021

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Approximately 30% of the world population suffers from immunoglobulin-E (IgE)-mediated allergy. IgE-mediated allergy affects the respiratory tract, the skin and the gastrointestinal tract and may lead to life-threatening acute systemic manifestations such as anaphylactic shock. The symptoms of allergy are mediated by IgE-recognition of causative allergen molecules from different allergen sources. Today, molecular allergy diagnosis allows determining the disease-causing allergens to develop allergen-specific concepts for prevention and treatment of allergy. Allergen-specific preventive and therapeutic strategies include allergen avoidance, vaccination, and tolerance induction. The implementation of these preventive and therapeutic strategies requires a detailed knowledge of the relevant allergen molecules affecting a given population. China is the world´s most populous country with around 1.4 billion inhabitants and an estimated number of more than 400 million allergic patients. Research in allergy in China has dramatically increased in the last decade. We summarize in this review article what is known about the dominating allergen sources and allergen molecules in China and what further investigations could be performed to draw a molecular map of IgE sensitization for China as a basis for the implementation of systematic and rational allergen-specific preventive and therapeutic strategies to combat allergic diseases in this country.

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“…Since the early description of allergen-induced histamine release from basophils (214) and the demonstration of the applicability of basophil activation testing for recombinant allergens (215), basophil activation testing has continuously developed (216). Importantly, basophil activation can discriminate between IgE-reactive antigens with no or poor ability to induce IgE-mediated receptor aggregation from potent allergens which induce basophil activation already at low doses (32,217). Thus basophil activation testing is useful to address a major problem of in vitro allergy diagnostics, i.e., the possibility of false-positive results due to the presence of crossreactive carbohydrate determinants (218).…”

Section: Molecular Allergy Diagnosismentioning

confidence: 99%

From Allergen Molecules to Molecular Immunotherapy of Nut Allergy: A Hard Nut to Crack

et al. 2021

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Peanuts and tree nuts are two of the most common elicitors of immunoglobulin E (IgE)-mediated food allergy. Nut allergy is frequently associated with systemic reactions and can lead to potentially life-threatening respiratory and circulatory symptoms. Furthermore, nut allergy usually persists throughout life. Whether sensitized patients exhibit severe and life-threatening reactions (e.g., anaphylaxis), mild and/or local reactions (e.g., pollen-food allergy syndrome) or no relevant symptoms depends much on IgE recognition of digestion-resistant class I food allergens, IgE cross-reactivity of class II food allergens with respiratory allergens and clinically not relevant plant-derived carbohydrate epitopes, respectively. Accordingly, molecular allergy diagnosis based on the measurement of allergen-specific IgE levels to allergen molecules provides important information in addition to provocation testing in the diagnosis of food allergy. Molecular allergy diagnosis helps identifying the genuinely sensitizing nuts, it determines IgE sensitization to class I and II food allergen molecules and hence provides a basis for personalized forms of treatment such as precise prescription of diet and allergen-specific immunotherapy (AIT). Currently available forms of nut-specific AIT are based only on allergen extracts, have been mainly developed for peanut but not for other nuts and, unlike AIT for respiratory allergies which utilize often subcutaneous administration, are given preferentially by the oral route. Here we review prevalence of allergy to peanut and tree nuts in different populations of the world, summarize knowledge regarding the involved nut allergen molecules and current AIT approaches for nut allergy. We argue that nut-specific AIT may benefit from molecular subcutaneous AIT (SCIT) approaches but identify also possible hurdles for such an approach and explain why molecular SCIT may be a hard nut to crack.

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Are the Terms Major and Minor Allergens Useful for Precision Allergology?

Cited by 40 publications

References 25 publications

IgE Epitopes of the House Dust Mite Allergen Der p 7 Are Mainly Discontinuous and Conformational

IgE Epitopes of the House Dust Mite Allergen Der p 7 Are Mainly Discontinuous and Conformational

The Molecular Allergen Recognition Profile in China as Basis for Allergen-Specific Immunotherapy

From Allergen Molecules to Molecular Immunotherapy of Nut Allergy: A Hard Nut to Crack

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