Abstract

Olive-pollen allergy is one of the leading causes of respiratory allergy in Mediterranean countries and some areas of North America. Currently, allergen-specific immunotherapy is the only etiophatogenic treatment. However, this approach is not fully optimal, safe, or effective. Thus, efforts continue in the search for novel immunotherapy strategies, being one of the most promising the use of peptides derived from major allergens. This work tries to determine the therapeutic potential and safety of 5 dodecapeptides derived from the main allergen of olive-pollen allergy, Ole e 1. The immunomodulatory capacity of these peptides was studied using peripheral blood mononuclear cells (PBMCs) obtained from 19 olive-pollen-allergic patients and 10 healthy controls. We determined the capacity of these peptides to inhibit the proliferative response toward olive-pollen allergenic extract and to induce the regulatory cytokines, IL-10 and IL-35. To test the safety and absence of allergenicity of the peptides, the basophil activation was analyzed by flow-cytometry, using peripheral blood. The results showed that two of five peptides inhibited near to 30% the proliferative response against the total olive-pollen allergenic extract in olive-pollen-allergic patients. Inhibition increased to nearly 35% when the 5 peptides were used in combination. In both cases, a statistically significant induction of IL-10 and IL-35 secretion was observed in the supernatants of allergic patients PBMCs cultures. None of the 5 peptides induced basophil activation and cross-link inflammatory cell-bound IgE. In conclusion, these results open up new possibilities in the treatment of olive-pollen allergy, which could solve some of the problems facing current therapy approaches.

Highlights

  • Olive-pollen allergy is one of the leading causes of respiratory allergy in Mediterranean countries and some areas of North America

  • Ole e 1 has at least 4 B-cell epitopes[16] and 2 regions, aa 91 to 102 and aa 119 to 130, which were defined as immunodominant T-cell epitopes, or the regions mainly recognized by olive-pollen-allergic patients, able to induce a T cell-proliferative response with no IgE-binding capability[17]

  • A pilot study of our group showed how stimulation with Ole e 1 peptides derived from the sequence of Ole e 1 obtained after Edman degradation[18], induced a different cytokine profile in peripheral blood mononuclear cells (PBMCs) from olive-pollen-allergic patients compared to nonallergic subjects

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Summary

Introduction

None of the 5 peptides induced basophil activation and cross-link inflammatory cell-bound IgE These results open up new possibilities in the treatment of olive-pollen allergy, which could solve some of the problems facing current therapy approaches. Immunotherapy based on modified allergens or peptides has been considered since more than 20 years, the last advances in molecular biology of allergens and the mechanisms implicated in their recognition and the modulation of their responses have increased the number of experimental and clinical trials to try to improve the immunotherapy guidelines, and the peptides therapy is one of the most promising treatments in course[8] This therapy for allergic disease involves the use of soluble allergen fragments of variable lengths and peptide-based vaccines, which could solve several of the main problems facing conventional AIT. We reported that these peptides were capable of modulating some genes implicated in the tolerance response, which could be of interest in the effort to develop a new immunomodulatory treatment[20]

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