Molecular approach to a patient's tailored diagnosis of the oral allergy syndrome

Abstract

Oral allergy syndrome (OAS) is one of the most common IgE-mediated allergic reactions. It is characterized by a number of symptoms induced by the exposure of the oral and pharyngeal mucosa to allergenic proteins belonging to class 1 or to class 2 food allergens. OAS occurring when patients sensitized to pollens are exposed to some fresh plant foods has been called pollen food allergy syndrome (PFAS). In the wake of PFAS, several different associations of allergenic sources have been progressively proposed and called syndromes. Molecular allergology has shown that these associations are based on IgE co-recognition taking place between homologous allergens present in different allergenic sources. In addition, the molecular approach reveals that some allergens involved in OAS are also responsible for systemic reactions, as in the case of some food Bet v 1-related proteins, lipid transfer proteins and gibberellin regulated proteins. Therefore, in the presence of a convincing history of OAS, it becomes crucial to perform a patient's tailored molecule-based diagnosis in order to identify the individual IgE sensitization profile. This information allows the prediction of possible cross-reactions with homologous molecules contained in other sources. In addition, it allows the assessment of the risk of developing more severe symptoms on the basis of the features of the allergenic proteins to which the patient is sensitized. In this context, we aimed to provide an overview of the features of relevant plant allergenic molecules and their involvement in the clinical onset of OAS. The value of a personalized molecule-based approach to OAS diagnosis is also analyzed and discussed.

Keywords: Allergen isoforms; Allergenic molecules; Class 1 food allergy; Class 2 food allergy; Food allergy; Isoallergens; Oral allergy syndrome; Oral cavity; Pollen-food allergy syndrome.

Fig. 1

Overview of the relationships between OAS, PFAS, class 1 and class 2 food allergens

Fig. 2

Comparison of amino acid sequence identity percentage between different allergens. Bar colors highlight the plant source of allergens, namely green, brown, yellow, red and light grey are for pollen, seed, fruit, root and latex, respectively. The similarity searches were performed with the Allergome Aligner tool, using the Blast algorithm on the Allergome platform (https://www.allergome.org). The amino acid sequence of Bet v 1.0101 (b and c), Bet v 2.0101 (a) and Cry j GRP (d) were used as query sequences. The allergens shown in a and b were selected as representative of the large number of homologs found in the database. When many homologs were found, that giving the highest identity with the query sequence was selected and shown in the figure. c represents a representative selection of Bet v 1 isoallergens/isoforms found in the Allergome database. The sequence identity values of GRP (d) were obtained with the algorithm CLUSTALO on the Uniprot website (https://www.uniprot.org) and they are referred to mature proteins lacking the signal peptide. Cup s 7 was not included because its complete sequence was not available. Additional details on the allergens shown in the Figure are reported in Additional file 1: Tables S1, S2, S3 and S4

Fig. 3

Schematic representation of cross-reactivity occurring between profilins (upper O-ring) and between Bet v 1-related allergenic proteins (lower O-ring) contained in pollens and plant foods. Red and green lines connecting allergy sources indicate single and double cross-reaction relationships, respectively. Arrowheads indicate the direction of data collection. The two pictures were generated on January 2020 by the Allergome software which uses information contained in the own database [53] (https://www.allergome.org)

Fig. 4

Schematic representation of the class 1 plant food allergens that may cause OAS and/or trigger allergic reactions in other organs and apparatus. These allergens may even induce severe anaphylaxis

Fig. 5

Sensitizations detected in 39 patients IgE-positive to at least one of the three analyzed GRP. The columns indicate, in order, patients sensitized to all the three GRP, those bi-sensitized to Cup s 7 and Pru p 3, to Cup s 7 and Pun g 7, to Pru p 7 and Pun g 7 and those monosensitized to Cup s 7, to Pru p 7 and to Pun g 7