Allergy is a hypersensitivity disease IgE-mediated, affecting more than 25% of the population. Actually the only curative treatment of allergies is Allergen-Specific Immunotherapy (SIT). Recombinant hypoallergenic allergen derivatives with reduced allergenic activity have been engineered to reduce side effects during SIT.Parietaria judaica (Pj) pollen contains two major allergens, Par j 1 and expressing disulphide bond variants of Par j 1 and Par j 2, was generated. The aim of this research project is to compare the immunological mechanisms activated by the major allergens of Pj and by rPjEDcys.In vitro analysis suggested that rPjEDcys has a reduced allergenity and maintains T cells reactivity. In particular we showed that PBMC of Pj allergic patients stimulated in vitro with the hybrid and the wild-type recombinant allergens scored a percentage of proliferating CD4+ and CD56+ cells higher than unstimulated samples. Furthermore, cytokine secretion assays on CD4+ cells demonstrated that rPjEDcys reduces the secretion of two Th2 cytokines that are critical in the development of allergy such as IL-5 and IL-13. Furthermore we observed the selection of a putative pTreg cell subset (defined as CD4+ CD25++ CD127-) in both the w.t. mixture and the rPjEDcys. We characterized these cells at molecular level by REAL-TIME PCR. Moreover, we addressed the kinetic of functional surface marker expression, such as GARP (Glycoprotein A Repetitions Predominant), LAP (Latency-Associated Peptide) and CD39 on CD4+ cells. Our analyses demonstrated that rPjEDcys induces a number of GARP-LAP-CD39 co-expressing cells higher than wild-type recombinant allergens. These results suggest that rPjEDcys represents a useful approach for immunotherapy of allergic disease.
|Numero di pagine||1|
|Stato di pubblicazione||Published - 2015|