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

Abstract

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.

Effect of chemical modifications on allergenic potency of peanut proteins

“…This is in line with observations made for modified Ara h 2/6 when using a solid-phase IgE-binding assay and findings of a recent study performed in European adult subjects. 15 We focused on conglutin storage Ara h 2 due to its high allergenic potency and resistance to digestive proteases pepsin and trypsin. In addition, Ara h 6 has a high homology of amino acid sequence to Ara h 2, especially in the middle part and at the C-terminal part of the protein from peanut.…”

“…14 These chemical modifications reduced the IgE-binding ϳ100-fold in solid-phase immunoassays without reducing T-cell immunogenicity. 15 An important question is whether the reduction of IgE-binding observed in solid-phase IgE-binding assays, such as the UniCAP system (Thermo Fisher Scientific, Portage, MI) and enzyme-linked immunosorbent assay, is functionally relevant. We sought to investigate the allergenicity of native and chemically modified CPE and the purified mix of Ara h 2 and Ara h 6 (Ara h 2/6) by using the in vitro mediator-release assay and passively sensitized with IgE antibodies from individuals with peanut allergy.…”

Chemically modified peanut extract shows increased safety while maintaining immunogenicity

“…The BAT assay, immunoblot, and T‐cell proliferation study were performed using sera of 9 Dutch peanut‐allergic patients. The clinical characteristics of these patients have been published previously . The study was approved by the Ethics Committee of the University Medical Centre Utrecht (approval number 08‐446).…”

“…Indirect basophil activation was performed using sera from 9 peanut‐allergic Dutch patients . Basophils from healthy donors were stripped and reloaded with IgE using plasma from the allergic patients.…”

“…Therefore, in our studies, a modification was chosen changing the three‐dimensional structure of Ara h 2 and 6. A similar approach was used for Pru p 3, the major peach allergen and previously investigated on the isolated allergens Ara h 2 and 6 . The structural similarity between Ara h 2 and Ara h 6, as well as the fact that they both contain disulfide bridges to maintain their structure, provide the possibility to decrease the allergenicity of these allergens using chemical modification.…”