Abstract and Introduction
Abstract
Subcutaneous allergen-specific immunotherapy has long been used in allergic rhinitis and/or asthma and has been recognized to be efficacious. However, owing to the inconvenience of injection and the risk of serious side effects, alternative concepts inspiring the search for effective noninjective routes, namely sublingual administration of allergens, have emerged. Sublingual immunotherapy (SLIT) appears to be associated with a lower incidence of systemic reactions. The clinical efficacy of subcutaneous immunotherapy (SCIT) is well established for both rhinitis and asthma. Meta-analyses relating to its efficacy on asthma and rhinitis are available. SLIT has also been validated in this respect. Comparative clinical studies of SLIT versus SCIT are scarce demonstrating both routes to be clinically efficient. Knowledge of the exact mechanism of action of SLIT has been increasing in the last decade. In addition, recent studies have proved similarities of the immunological changes with the treatment of both routes. Further comparative clinical and immunological studies of SLIT versus SCIT are needed to confirm the long-term efficacy and to complete the knowledge of immunological mechanisms of both routes. Moreover, better understanding of the interaction of allergen and oral mucosal dendritic cells during SLIT may allow improved targeting of SLIT vaccines.
Introduction
The prevalence of allergic diseases, including asthma, rhinitis and eczema, has been increasing for the last two decades in developed and developing countries and its burden is substantial.[1,2] The mainstay treatments are patient education, allergen avoidance where feasible, pharmacotherapy for symptom relief and, when appropriate, allergen-specific immunotherapy.[3]
Specific allergen immunotherapy is the only treatment modality with the capacity of changing the natural course of allergic disease, hence preventing its exacerbation,[3] and might halt progression from rhinitis to asthma.[4]
Since its discovery, specific immunotherapy (SIT) has been commonly performed by the subcutaneous route. However, in early studies, subcutaneous immunotherapy (SCIT) was associated with uncommon, but severe or even fatal, systemic reactions.[5] As a consequence, the interest in alternative routes increased, inspiring the search for more effective noninjection routes of administration of specific allergen immunotherapy. Therefore, delivery of allergens through the mucosal route have been proposed, and it has been suggested that the natural mechanisms underlying the induction of oral tolerance at mucosal surfaces may be an effective therapeutic strategy for suppression of ongoing pathological immune responses in allergic diseases.[6] Various mucosal routes of administration were proposed and investigated during the last decades, involving local oral, nasal, bronchial and sublingual routes. Controlled trials failed to demonstrate clinical efficacy of oral and bronchial routes, therefore those routes have been abandoned. Although local nasal immunotherapy proved to be effective in a number of controlled trials,[7–11] owing to the high incidence of reported side effects and the requirement of a particular administration technique, the use of this technique has declined. Meanwhile, the efficacy and safety of the sublingual route was documented by numerous controlled trials in children and adults with asthma and rhinitis sensitized to house dust mite (HDM) or pollen.[12,13] Furthermore, long-lasting and steroid-sparing[14] effects have been documented with a preventive effect on the progression of the allergic disease and the development of asthma.[15,16] Moreover, our understanding of the underlying immunological mechanism is substantially increasing.
Subcutaneous immunotherapy has the capacity of skewing T-cell immune response from Th2- to Th1-type related to an increased IFN-γ and IL-12 production, with a reduction in Th2 activity through a mechanism of anergy or tolerance, the latter being related to the generation of allergen-specific Tregs, which are capable of producing cytokines such as IL-10 and TGF-β.[17] The sublingual route of administration was suggested to have similar mechanisms as SCIT,[18] with a particular involvement of mucosal dendritic cells (DCs).[19]
In this article, clinical efficacy, safety and immunological mechanisms based on currently available data will be presented and those two modes of specific immunotherapy will be compared in these aspects.
Immunotherapy. 2011;3(6):747-756. © 2011 Future Medicine Ltd.
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