Peptide epitopes as biomarkers of soya sensitization in rBet v 1 immunotherapy of birch‐related soya allergy

Abstract

Background: There are no diagnostic and/or prognostic markers of the treatment outcome in patients receiving allergen immunotherapy (AIT). Although numerous allergen epitopes are known, their value in this context has not been investigated. This paper deals with re-evaluation of sera from patients who underwent AIT against rBet v 1 for treatment of their soya allergy (BASALIT trial).Objective: To evaluate the diagnostic and/or prognostic potential of allergen epitopes recognition by antibodies from patients with birch-related soya allergy before and after rBet v 1-immunotherapy.Methods: PR-10 epitope-binding profiles from 34 patients were identified in silico using a statistical peptide phage display at start and at end of AIT. IgE-and IgG-binding to these peptide epitopes was measured in peptide microarrays. Clinical relevance of epitopes was evaluated by comparing these measurements to a number of treatment outcome measures recorded during double-blind placebo-controlled food challenge at start and end of AIT. Results:We showed that IgG-and IgE-recognition of peptide epitopes after AIT were surrogate markers of 5 out of 12 analysed treatment outcome measures using this patient cohort. Seven epitopes were identified from multiple PR-10 allergen sequences.Twenty-six peptide epitopes were used for IgG and IgE measurements. IgE-binding to one of the epitopes was associated with stronger intensity of oral tingling/itching after ingesting soya at start of AIT. IgG recognizing two other epitopes at start of AIT could predict decreased Cor a 1-specific IgE concentration (p = .043) and decreased lip swelling intensity (p = .016) after AIT. Tolerance to increasing amounts of soy at food challenge correlated with IgG-binding to another epitope at start of AIT (p = .046). Conclusion:IgG-and IgE-binding to peptide epitopes in PR-10 is a potential indicator of the outcome and clinical course of AIT of soya-sensitized patients with rBet v 1.

Entwicklungen und Perspektiven in der Allergologie

“…24 Inwieweit eine Epitopkartierung (epitope mapping) diesbezüglich hilfreich sein kann, bedarf ebenfalls noch weiterer Untersuchungen. 16 Neue Therapieformen richten sich entweder gegen das Allergen selbst, greifen in den Signalweg der allergischen Entzündung ein oder zielen auf die Modulation der IgE-Produktion ab.…”

Developments and perspectives in allergology

“…24 The extent to which epitope mapping can be helpful here also requires further investigation. 16 New therapies are either directed against the allergen itself, interfere with the pathway of allergic inflammation, or target the modulation of IgE production.…”

“…An allergen immunotherapy against pollen allergens appears to have beneficial effects on pollen‐associated food allergy in selected patients 15 . Unfortunately, there are not yet any biomarkers that can predict efficacy 16 …”

“…For monitoring the clinical efficacy of AIT, the European Academy of Allergy and Clinical Immunology (EAACI) lists a number of potential biomarkers, which, however, cannot yet be used in routine clinical practice 24 . The extent to which epitope mapping can be helpful here also requires further investigation 16 …”

Mechanisms and biomarkers of successful allergen-specific immunotherapy

“…Another CM-OIT study developed predictive models based on epitope-specific antibody binding and showed that having lower diversity and lower binding of IgE at baseline to specific epitopes can predict SU [ 170 ]. Lastly, a study investigating the efficacy of subcutaneous injection of birch pollen allergen Bet v 1 in soya allergy reported the potential of IgE- and IgG-binding to epitopes as a biomarker for successful AIT [ 171 ].…”