Therapeutic Potential of Monoclonal IgA Antibodies in Allergic Diseases: Suppressive Effect of IgA on Immune Responses Induced By Re-exposure to Antigen in Sensitized Mice by Monoclonal IgE Antibody That Binds to a Different Epitope of the Same Antigen

Repeated exposure to an allergen induces allergic symptoms by activating mast cells that express anti-allergen IgE, which results in further sensitization to an allergen. Considering that additional sensitization elicits more severe allergic reactions upon the next allergen challenge, suppression of the boosting phase represents an efficacious way to prevent and ameliorate allergic diseases. In this study, we investigated the therapeutic potential of allergen-specific monoclonal IgA on allergic diseases. This antibody acts by decreasing immune responses upon exposure to allergens in mice previously sensitized by a monoclonal IgE that recognizes the allergen. The lack of inhibitory effects of anti-ovalbumin monoclonal IgA (OA-4) on either the binding of anti-ovalbumin monoclonal IgE (OE-1) to ovalbumin by ELISA or on ovalbumin-induced degranulation of rat basophilic leukemia RBL2H3 cells sensitized with OE-1 indicated that OA-4 and OE-1 recognized different epitopes on ovalbumin. Immune responses (anti-ovalbumin IgG1 production and cytokine release from splenocytes) induced by intravenous ovalbumin challenge in DBA/1J mice passively sensitized with OE-1 were inhibited by intravenous injection of OA-4 15 min before challenge without affecting anaphylaxis. Moreover, OA-4 injection 1 h after ovalbumin challenge also effectively suppressed immune responses. The achievement of immunosuppression by IgA injection occurred even after allergen challenge in mice in an epitope-independent fashion. These findings suggest that monoclonal IgA administered at the time of hospitalization of a patient with allergic symptoms, who was already exposed to the allergen in the presence of IgE recognizing an undefined epitope(s) on the allergen, should effectively relieve allergic disease through its immunosuppressive effects.