Characterization of recombinant Mal d 4 and its application for component-resolved diagnosis of apple allergy

Y. Ma, L. Zuidmeer, B. Bohle, S. T. H. Bolhaar, G. Gadermaier, E. Gonzalez-Mancebo, M. Fernandez-Rivas, A. C. Knulst, M. Himly, R. Asero, C. Ebner, R. van Ree, F. Ferreira, H. Breiteneder, K. Hoffmann-Sommergruber

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Abstract

BACKGROUND: Profilins are ubiquitous panallergens that have been extensively characterized; yet, their clinical relevance is still unclear. OBJECTIVE: The aim of the present study was to produce recombinant apple profilin (rMal d 4) and to evaluate its allergenic activity and its potency for component-resolved allergy diagnosis. METHODS: Complementary DNA-derived Mal d 4 was cloned, expressed in Escherichia coli and subsequently purified via poly (l-proline) sepharose. A total of 28 sera from apple-allergic patients were used for IgE-ELISA, immunoblot, RAST and basophil histamine release (BHR) test. In addition, skin prick tests (SPTs) were performed in five patients. RESULTS: Four different complementary DNA coding for apple profilin, Mal d 4, each with an open reading frame of 393 nucleotides, were identified. One isoform Mal d 4.0101 was expressed in Escherichia coli and subsequently purified. Mass spectroscopy revealed the expected mass of 13.826 for rMal d 4.0101, and circular dichroism analysis data were typical for a folded protein and small-angle X-ray scattering measurement identified the protein as a monomer. All the serum samples displayed IgE binding to rMal d 4.0101 in IgE ELISA, immunoblot and RAST. In immunoblotting, IgE binding to natural Mal d 4 was partially/completely inhibited by preincubation with rMal d 4.0101, and RAST values to apple extract were significantly reduced upon serum pretreatment with rMal d 4.0101. SPTs and BHR assays using purified rMal d 4.0101 were positive. Purified rMal d 4.0101 was destroyed within seconds when subjected to pepsin digestion. CONCLUSIONS: Apple profilin complementary DNAs were identified. The physicochemical and allergenic properties of purified recombinant Mal d 4.0101 were evaluated showing that the recombinant protein was equal to the natural protein as shown by inhibition assays. Thus, Mal d 4 represents another example suitable for component-resolved diagnosis of food allergy
Original languageEnglish
Pages (from-to)1087-1096
JournalClinical and experimental allergy
Volume36
Issue number8
DOIs
Publication statusPublished - 2006

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