When the Frequencies of Sensitization and Elicitation of Allergic Reaction Do Not Correlate—The Case of Apple Gibberellin-Regulated Protein Tested in an Italian Population

Background. Literature reports describing allergic symptoms against apple in patients sensitized to gibberellin-regulated proteins (GRP) suggested the presence of an allergenic GRP in this fruit. Objective. The aim of this study was the assessment of the presence of a GRP protein in apple and the investigation of its allergenicity. Methods. The protein was isolated and identified by classical biochemical methods. Bioinformatics tools were used for similarity searches and molecular modelling. The immunological features were investigated using the multiplex FABER test. Clinical data were collected by allergy specialists. Results. A GRP was detected in the apple peel and pulp and it was named applemaclein. This protein displays 94% of sequence identity with peamaclein, Pru p 7, representing the prototype of this allergen family. The applemaclein molecular model shows a very irregular surface with grooves/clefts that may potentially accommodate small molecular ligands. In a population of 4721 Italian patients, apple GRP shows a frequency of sensitization higher than that of the peach, pomegranate and cypress pollen homologs. However, in a cohort of Italian patients, most of individuals IgE positive to apple GRP did not report allergic reactions against this fruit. Conclusion. Compared to the peach Pru p 7, applemaclein shows some different structural features and higher sensitization frequency, which is often not associated with allergic reactions against apple. Further studies are needed to understand a possible correlation between the applemaclein structural properties, the interaction with still unknown molecules and the immunological behavior.