Article

Mechanisms of allergen-specific desensitization

Cytos Biotechnology AG, Zurich-Schlieren, Switzerland.
The Journal of allergy and clinical immunology (Impact Factor: 11.48). 08/2010; 126(2):375-83. DOI: 10.1016/j.jaci.2010.05.040
Source: PubMed

ABSTRACT

Allergen-specific desensitization (SIT) is the most effective therapy for allergies. Although allergen-specific antibodies have an important role in the process, mechanisms of IgG-mediated inhibition of allergic reactions are not well defined.
We investigated mechanisms by which SIT-induced allergen-specific IgGs inhibit allergic reactions.
We generated mAbs that recognize 3 nonoverlapping epitopes of the major cat allergen Fel d 1. Each of the mAbs was produced as an IgE and different IgG isotype.
IgEs against 2 nonoverlapping epitopes on Fel d 1 are necessary and sufficient to sensitize mast cells for maximal FcepsilonRI signaling and degranulation on exposure to monomeric Fel d 1. IgE antibodies of a third specificity did not further increase mast cell degranulation, indicating that formation of large FcepsilonRI clusters are not required to induce maximal activation of mast cells. A single IgG that was specific for an epitope different from those recognized by the IgEs was a potent inhibitor of Fel d 1-mediated mast cell activation in vitro and in vivo. This inhibition required Fcgamma receptor-IIB. In human beings, IgGs of a single specificity were able to block degranulation of basophils from individuals with cat allergy. The inhibitory potential of these antibodies increased when larger allergen-IgG complexes were formed.
These data reconcile conflicting theories in the literature and might explain the reason IgE levels do not necessarily decrease during therapy, despite clinical efficacy. These findings have important implications for vaccine design.

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    • "Specific immunotherapy currently represents the only treatment that modifies the natural history of allergic rhinitis [27] with proven clinical effectiveness [30]. However, despite the effects of this treatment being relatively well described, including important immunologic changes, like a modulation of the T-cell profile, with induction of allergen-specific Treg cells, that inhibit a proliferative and cytokine response to the allergen [31,32] or a local decrease in mast cell and basophil activity [33,34]. The systemic impact of SCIT in AR patients mono-sensitized to Dpt, as well as, the repercussion of long-term treatment on the effector cells of the allergic inflammation, are widespread under research. "
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