Mechanisms of allergen immunotherapy for inhaled allergens and predictive biomarkers

Allergen immunotherapy is effective in patients with IgEdependent allergic rhinitis and asthma.When immunotherapy is given continuously for 3 years, there is persistent clinical benefit for several years after its discontinuation.This diseasemodifying effect is both antigen-specific and antigen-driven.Clinical improvement is accompanied by decreases in numbers of effector cells in target organs, including mast cells, basophils, eosinophils, and type 2 innate lymphoid cells.Immunotherapy results in the production of blocking IgG/IgG 4 antibodies that can inhibit IgE-dependent activation mediated through both high-affinity IgE receptors (FcεRI) on mast cells and basophils and low-affinity IgE receptors (FcεRII) on B cells.Suppression of T H 2 immunity can occur as a consequence of either deletion or anergy of antigen-specific T cells; induction of antigenspecific regulatory T cells; or immune deviation in favor of T H 1 responses.It is not clear whether the altered long-term memory resides within the T-cell or the B-cell compartment.Recent data highlight the role of IL-10-producing regulatory B cells and ''protective'' antibodies that likely contribute to long-term tolerance.Understanding mechanisms underlying induction and persistence of tolerance should identify predictive biomarkers of clinical response and discover novel and more effective strategies for immunotherapy.(