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: The literature reports describing allergic symptoms against apples in thepatients sensitized to the gibberellin-regulated proteins (GRPs) suggested the presenceof an allergenic GRP in this fruit.Objective: This study aimed to assess the presence of a GRP protein in apples andinvestigate its allergenicity.Methods: The protein was isolated and identified by the classical biochemical methods.The bioinformatics tools were used for similar searches and molecular modeling. Theimmunological features were investigated using the multiplex FABER test. Clinical datawere collected by the allergy specialists.Results: A GRP was detected in the apple peel and pulp and it was namedapplemaclein. This protein displays 94% of sequence identity with peamaclein, Pru p7, representing the prototype of this allergen family. The applemaclein molecular modelshows a very irregular surface with grooves/clefts that may potentially accommodatesmall molecular ligands. In a population of 4,721 patients in Italy, 187 (4.0%) weresensitized to any allergenic GPR. Of those, 115 (61.5%), 61 (32.6%), 30 (16.0%), and 99(52.9%) had immunoglobulin E (IgE) to apple, peach, pomegranate, and cypress GRP,respectively. However, in a cohort of the patients in Italy, most individuals IgE positive tothe apple GRP did not report allergic reactions against this fruit.Conclusion: Compared with the peach Pru p 7, applemaclein shows some differentstructural features and higher sensitization frequency, which is often not associated withallergic reactions against apple. Further studies are needed to understand a possiblecorrelation between the applemaclein structural properties, the interaction with stillunknown molecules, and immunological behavior.