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 mannitolspecific
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.