1. 2S protein Ara h 7.0201 has unique epitopes compared to other Ara h 7 isoforms and is comparable to 2S proteins Ara h 2 and 6 in basophil degranulation capacity
- Author
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Hayen, S.M., Ehlers, A.M., den Hartog Jager, C.F., Garssen, J., Knol, E.F., Knulst, A.C., Suer, W., Willemsen, L.E.M., Otten, H.G., Afd Pharmacology, Pharmacology, Afd Pharmacology, and Pharmacology
- Subjects
Models, Molecular ,0301 basic medicine ,double blind procedure ,Protein Conformation ,Fibrinogen receptor ,HLA DR antigen ,Basophil ,Immunoglobulin E ,Cell Degranulation ,Epitope ,law.invention ,immunoglobulin E ,Epitopes ,basophil ,0302 clinical medicine ,law ,Protein Isoforms ,Immunology and Allergy ,heterocyclic compounds ,receptor type tyrosine protein phosphatase C ,Allergens and epitopes ,Non-U.S. Gov't ,comparative study ,peanut extract ,epitope ,clinical article ,biology ,predictive value ,Chemistry ,adult ,Research Support, Non-U.S. Gov't ,article ,food and beverages ,peanut allergy ,Middle Aged ,Basophils ,unclassified drug ,trypsin ,medicine.anatomical_structure ,CD123 antigen ,female ,priority journal ,allergenicity ,ara h 7 isoform ,sequence alignment ,Recombinant DNA ,isoprotein ,lipids (amino acids, peptides, and proteins) ,blood sampling ,diagnostic accuracy ,IgE ,immunoblotting ,2S Albumins, Plant ,amino acid substitution ,cross linking ,Immunology ,Research Support ,Basophil degranulation ,Structure-Activity Relationship ,03 medical and health sciences ,male ,fibrinogen receptor ,Food allergy ,medicine ,Journal Article ,Humans ,Peanut Hypersensitivity ,controlled study ,Amino Acid Sequence ,human ,albumin ,hydrophobicity ,food allergy ,carboxy terminal sequence ,nonhuman ,basophil degranulation ,human cell ,pepsin A ,prediction ,sequence homology ,Antigens, Plant ,biochemical phenomena, metabolism, and nutrition ,Molecular biology ,carbohydrates (lipids) ,Basophil activation ,030104 developmental biology ,allergens and epitopes ,030228 respiratory system ,basophil activation test ,biology.protein ,ara h 6 isoform ,Blood sampling - Abstract
Background: Screening for specific IgE against 2S albumin proteins Ara h 2 and 6 has good positive predictive value in diagnosing peanut allergy. From the third 2S member Ara h 7, 3 isoforms have been identified. Their allergenicity has not been elucidated. Objective: This study investigated the allergenicity of Ara h 7 isoforms compared to Ara h 2 and 6. Methods: Sensitization of 15 DBPCFC-confirmed peanut-allergic patients to recombinant Ara h 2.0201, Ara h 6.01 and isoforms of recombinant Ara h 7 was determined by IgE immunoblotting strips. A basophil activation test (BAT) was performed in 9 patients to determine IgE-cross-linking capacities of the allergens. Sensitivity to the allergens was tested in 5 patients who were sensitized to at least 1 Ara h 7 isoform, by a concentration range in the BAT. 3D prediction models and sequence alignments were used to visualize differences between isoforms and to predict allergenic epitope regions. Results: Sensitization to Ara h 7.0201 was most frequent (80%) and showed to be equally potent as Ara h 2.0201 and 6.01 in inducing basophil degranulation. Sensitization to Ara h 7.0201 together with Ara h 2.0201 and/or 6.01 was observed, indicating the presence of unique epitopes compared to the other 2 isoforms. Differences between the 3 Ara h 7 isoforms were observed in C-terminal cysteine residues, pepsin and trypsin cleavage sites and 3 single amino acid substitutions. Conclusion & clinical relevance: The majority of peanut-allergic patients are sensitized to isoform Ara h 7.0201, which is functionally as active as Ara h 2.0201 and 6.01. Unique epitopes are most likely located in the C-terminus or an allergenic loop region which is a known allergenic epitope region for Ara h 2.0201 and 6.01. Due to its unique epitopes and allergenicity, it is an interesting candidate to improve the diagnostic accuracy for peanut allergy.
- Published
- 2018