Modeling the conversion between specific IgE test platforms for nut allergens in children and adolescents

Hoang, Jennifer; Çelik, Alper; Lupinek, Christian; Valenta, Rudolf; Duan, Lucy; Dai, Ruixue; Brydges, May; Dubeau, Aimée; Lépine, C; Wong, Samantha; Alexanian‐Farr, Mara; Magder, Ahuva; Subbarao, Padmaja; Upton, Julia; Schmidthaler, Klara; Szépfalusi, Zsolt; Eiwegger, Thomas

doi:10.1111/all.14529

Cited by 14 publications

(13 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The availabilities of single allergens and advanced microarray technology have made it possible to obtain a quick insight into the sensitization profile of a patient ( 210 ). In order to enable quantitative conversion between different multiplex IgE test-platforms for nut allergens, statistical models have been established recently ( 211 ). For the European MeDALL research project, an allergen chip with 170 allergen molecules, including natural purified and recombinant allergens from almond, cashew, pistachio and peanut, was developed which could be used even for dried blood samples ( 212 ).…”

Section: Diagnosis Of Nut Allergymentioning

confidence: 99%

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

et al. 2021

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Diagnosis Of Nut Allergymentioning

confidence: 99%

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

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Spearman correlations with ImmunoCAP exceeded 0.9 for Timothy grass and birch and also for most of the major component allergens. The EUROLINE was also used as a comparator in the previously mentioned study by Hoang et al 41 The key finding was that the EUROLINE reported more positive sensitizations to certain allergens, including hen's egg, cow's milk, and almond than either ALEX or the ISAC-related MeDALL chip. This may well be explained by the fact that the amount of allergen on the solid phase is greater for the immunoblot-based EUROLINE than for the microarray assays.…”

Section: Studies That Investigated Other Multiplex Assaysmentioning

confidence: 99%

The use of microarray and other multiplex technologies in the diagnosis of allergy

Keshavarz

Platts‐Mills

Wilson

2021

Annals of Allergy, Asthma & Immunology

View full text Add to dashboard Cite

Multiplex assays, which can measure immunoglobulin E to several allergens simultaneously in a single assay, have emerged as an alternative to traditional skin testing and singleplex assays.Not currently approved for clinical use in the United States, Immuno Solid-Phase Allergen Chip and other multiplex assays are approved and used as part of clinical practice in Europe and Asia.The advantages of multiplex technology, including the extensive immunoglobulin E profiling afforded from only a small sample of serum, have to be balanced against considerations of cost, sensitivity, and extraneous data.The major strength of multiplex assays at this time likely remains for research applications; however, ongoing advances and innovations in multiplex technology can eventually be expected to be integrated as an important tool in clinical diagnosis and management.

show abstract

“…To our knowledge, no plant-produced recombinant allergen is used in any of the commercially available singleplex or multiplex diagnostic assays. Molecular allergy diagnosis of peanut allergy is performed with either natural or E. coli -produced rAra h 2 in the singleplex ImmunoCAP (r) assay (Park et al, 2018 ) and in multiplex assays, such as the ImmunoCAP ISAC (r) (Gadisseur et al, 2011 ), the experimental MeDALL-chip (n) (Lupinek et al, 2014 ), or the ALEX allergy explorer (r) (Hoang et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

The Major Peanut Allergen Ara h 2 Produced in Nicotiana benthamiana Contains Hydroxyprolines and Is a Viable Alternative to the E. Coli Product in Allergy Diagnosis

et al. 2021

View full text Add to dashboard Cite

Peanut allergy is a potentially life-threatening disease that is mediated by allergen-specific immunoglobulin E (IgE) antibodies. The major peanut allergen Ara h 2, a 2S albumin seed storage protein, is one of the most dangerous and potent plant allergens. Ara h 2 is posttranslationally modified to harbor four disulfide bridges and three hydroxyprolines. These hydroxyproline residues are required for optimal IgE-binding to the DPYSPOHS motifs representing an immunodominant IgE epitope. So far, recombinant Ara h 2 has been produced in Escherichia coli, Lactococcus lactis, Trichoplusia ni insect cell, and Chlamydomonas reinhardtii chloroplast expression systems, which were all incapable of proline hydroxylation. However, molecular diagnosis of peanut allergy is performed using either natural or E. coli-produced major peanut allergens. As IgE from the majority of patients is directed to Ara h 2, it is of great importance that the recombinant Ara h 2 harbors all of its eukaryotic posttranslational modifications. We produced hydroxyproline-containing and correctly folded Ara h 2 in the endoplasmic reticulum of leaf cells of Nicotiana benthamiana plants, using the plant virus-based magnICON® transient expression system with a yield of 200 mg/kg fresh biomass. To compare prokaryotic with eukaryotic expression methods, Ara h 2 was expressed in E. coli together with the disulfide-bond isomerase DsbC and thus harbored disulfide bridges but no hydroxyprolines. The recombinant allergens from N. benthamiana and E. coli were characterized and compared to the natural Ara h 2 isolated from roasted peanuts. Natural Ara h 2 outperformed both recombinant proteins in IgE-binding and activation of basophils via IgE cross-linking, the latter indicating the potency of the allergen. Interestingly, significantly more efficient IgE cross-linking by the N. benthamiana-produced allergen was observed in comparison to the one induced by the E. coli product. Ara h 2 from N. benthamiana plants displayed a higher similarity to the natural allergen in terms of basophil activation due to the presence of hydroxyproline residues, supporting so far published data on their contribution to the immunodominant IgE epitope. Our study advocates the use of N. benthamiana plants instead of prokaryotic expression hosts for the production of the major peanut allergen Ara h 2.

show abstract

Modeling the conversion between specific IgE test platforms for nut allergens in children and adolescents

Cited by 14 publications

References 33 publications

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

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

The use of microarray and other multiplex technologies in the diagnosis of allergy

The Major Peanut Allergen Ara h 2 Produced in Nicotiana benthamiana Contains Hydroxyprolines and Is a Viable Alternative to the E. Coli Product in Allergy Diagnosis

Contact Info

Product

Resources

About