Chemical modification of peanut conglutin reduces I g E reactivity but not T cell reactivity in peanut‐allergic patients

Summary Background Specific immunotherapy for peanut allergy is associated with significant side‐effects. Chemically modified allergens may provide a safer alternative. Objective This study aimed to analyse the immunogenicity and allergenicity of modified peanut conglutin. Methods Native peanut conglutin and two modifications thereof were generated ( RA and RAGA ). Conglutin‐specific T cell lines from 11 peanut‐allergic patients were analysed for proliferation and cytokine production. Sera from 14 patients were analysed for I g E / I g G 1/ I g G 4 binding by immunoblot and ELISA . IgE reactivity was analysed by direct and indirect basophil activation test ( BAT ), in presence and absence of patient plasma or CD 32‐blocking antibodies. Results T cell proliferation to RA was unchanged, and proliferation to RAGA was reduced compared to native conglutin. Cytokine profiles remained unchanged. I g E , I g G 1 and I g G 4 binding to RA and RAGA was significantly reduced. In the direct BAT , the relative potency of modified conglutin was decreased in 67% and increased/similar in 33% of the patients. In the indirect BAT , RA and RAGA were 10–100 times less potent than native conglutin. Addition of plasma to the indirect BAT increased the relative potency of modified conglutin in patients with high peanut‐specific I g G levels. This was mediated via blocking of the response to native conglutin, most likely by soluble I g G , and not via CD 32. Conclusion and Clinical Relevance Chemical modification of peanut conglutin by RA retains immunogenicity and reduces allergenicity and may be a promising approach for development of a curative treatment for peanut allergy. In a subgroup of patients, where the reactivity of native conglutin is already partially blocked by I g G , the effect of the modification of conglutin is less pronounced.