Allergen immunotherapy for allergic respiratory diseases

Abstract

Allergen specific immunotherapy involves the repeated administration of allergen products in order to induce clinical and immunologic tolerance to the offending allergen. Immunotherapy is the only etiology-based treatment that has the potential for disease modification, as reflected by longterm remission following its discontinuation and possibly prevention of disease progression and onset of new allergic sensitizations. Whereas subcutaneous immunotherapy is of proven value in allergic rhinitis and asthma there is a risk of untoward side effects including rarely anaphylaxis. Recently the sublingual route has emerged as an effective and safer alternative. Whereas the efficacy of SLIT in seasonal allergy is now well-documented in adults and children, the available data for perennial allergies and asthma is less reliable and particularly lacking in children. This review evaluates the efficacy, safety and longterm benefits of SCIT and SLIT and highlights new findings regarding mechanisms, potential biomarkers and recent novel approaches for allergen immunotherapy.

Keywords: adjuvant; allergen vaccine; immunopotentiator; sublingual immunotherapy; vector system.

Figure 1. Immunological mechanisms of immunotherapy to aeroallergens (SCITandSLIT). Reproduced with kind permission of Dr M Shamji and Clin Exp Allergy. Low-dose and repeated allergen exposure at mucosal surfaces in atopic individuals results in Th2-T lymphocyte-driven, IgE-mediated allergic responses in tyarget organs. In contrast, high-allergen exposure that occurs with immunotherapy results in a shift of T cell polarization. The induction of T regulatory cells [inducible Treg cells (iTreg) and natural Treg cells (nTreg)] and cytokines such as IL-10 and TGF-beta suppress effector T cell responses. There is also observed a shift from T helper 2 (Th2) to T helper 1 (Th1) T lymphocyte responses. These altered T cell responses contribute to the induction of allergen-specific IgG, and in particular IgG4 antibody responses, and also an increase in IgA. IgG antibodies compete with IgE for allergen and suppress both FceRI- mediated basophil/mast cell activation and IgE-Facilitated CD23-dependent allergen presentation to T cells. There is good evidence that these mechanisms operate for immunotherapy via both the subcutaneous and sublingual routes. It is likely that for SLIT there are additional local mechanisms involving interactions between recirculating dendritic cells and T cells in the regional lymph glands and nasal mucosa – since the cervical lymph chain serve both the nasal mucosa and the floor of the mouth.