Allergen IgE-isotype-specific suppression by maternally derived monoclonal anti-IgG-idiotype

The dramatic increase of IgE-mediated allergic diseases in western countries demonstrates the urgent need for new therapeutic or prophylactic approaches. In mice, a prophylactic long-lasting allergen-specific suppression of IgE responsiveness is induced by maternal IgG antibodies to allergens like ovalbumin, phospholipase A(2) (bvPLA(2)) or ovomucoid. As neonatal application or maternally derived pathogen-reactive antibodies (idiotypes) as well as corresponding anti-idiotypes can induce anti-microbial protection, we probed the transgenerational IgE-suppressive mechanism with a syngeneic monoclonal anti-idiotypic antibody.

The monoclonal bee-venom-phospholipase A(2) (bvPLA(2))-reactive IgG antibody MS613 (idiotype) or the corresponding syngeneic anti-idiotype II/2-19 were injected during the first 2 days postpartum to the dams. Immunization of offspring with minute doses of IgE-inducing bvPLA(2) was started at an adult age of 3(1/2) months.

The postnatal transfer of the anti-bvPLA(2) idiotype MS613 or the corresponding anti-idiotype II/2-19 induced long-lasting allergen-specific IgE suppression in a dose-dependent manner, while the IgG response to the allergen developed normally. Quantitatively, the anti-idiotype was more effective than idiotype. Molecular modeling of the idiotype-anti-idiotype complex and its comparison with the bvPLA(2) structure revealed that the anti-idiotype does not mimic bvPLA(2) epitopes and thus can not be regarded as an internal image antibody and, consequently, does not function as a surrogate antigen.

Idiotypic network reactivity is at least one major factor for induction of transgenerational IgE suppression by maternal IgG antibodies. If applicable to humans, these data suggest the possibility of a prophylactic and possibly therapeutic treatment of IgE-mediated allergic diseases with anti-idiotypic antibodies.