Chemical modification of peanut conglutin reduces IgE reactivity but not T cell reactivity in peanut-allergic patients

Abstract

Specific immunotherapy for peanut allergy is associated with significant side-effects. Chemically modified allergens may provide a safer alternative. This study aimed to analyse the immunogenicity and allergenicity of modified peanut conglutin. 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 IgE/IgG1/IgG4 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 CD32-blocking antibodies. T cell proliferation to RA was unchanged, and proliferation to RAGA was reduced compared to native conglutin. Cytokine profiles remained unchanged. IgE, IgG1 and IgG4 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 IgG levels. This was mediated via blocking of the response to native conglutin, most likely by soluble IgG, and not via CD32. 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 IgG, the effect of the modification of conglutin is less pronounced.