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
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.
(2018) Clinical and Experimental Allergy, volume 48, issue 7, pp. 890 - 897
(Article)
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
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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.
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Keywords: allergens and epitopes, basophil, food allergy, IgE, albumin, ara h 6 isoform, ara h 7 isoform, CD123 antigen, epitope, fibrinogen receptor, HLA DR antigen, immunoglobulin E, isoprotein, peanut extract, pepsin A, receptor type tyrosine protein phosphatase C, trypsin, unclassified drug, adult, allergenicity, amino acid substitution, article, basophil activation test, basophil degranulation, blood sampling, carboxy terminal sequence, clinical article, comparative study, controlled study, cross linking, diagnostic accuracy, double blind procedure, female, human, human cell, hydrophobicity, immunoblotting, male, nonhuman, peanut allergy, prediction, predictive value, priority journal, sequence alignment, sequence homology
ISSN: 0954-7894
Publisher: Blackwell Publishing Ltd
(Peer reviewed)