A hypothesis for the mechanism of immediate hypersensitivity to mannitol

Immediate hypersensitivity reactions to mannitol present naturally in pomegranate (Punica granatum) and cultivated mushroom (Agaricus bisporus) have appeared in the medical literature recently. Mannitol, being inert, cannot react with proteins to form a hapten-carrier conjugate and elicit an immune response. Therefore, it is important to understand the mechanism of immediate hypersensitivity to this sugar alcohol. A likely mechanism was conceptualized to explain how an individual can become sensitized to mannitol and how free mannitol can elicit an anaphylactic reaction in the sensitized individual. The proposed mechanism for sensitization involves the reaction of D-mannose with exposed amino groups of proteins in vivo to form Schiff base intermediates bearing a D-mannitoyl moiety, which closely resembles D-mannitol. This intermediate appears to be responsible for eliciting the formation of mannitol-specific IgE in susceptible individuals. Once an individual is sensitized with the formation of mannitol-specific IgE, mannitol can cause anaphylactic reactions by acting either as a univalent anaphylactogen or a bivalent hapten. The Schiff base intermediate bearing the mannitoyl moiety appears to act as a true sensitizer, whereas D-mannose appears to act as prosensitizer and D-mannitol acts as a non-sensitizing elicitor. This hypothesis can also explain the mechanism of sensitization and IgE-mediated hypersensitivity to any sugar alcohol.