Antigen Presentation by Dendritic Cells and the Practice of Immunotherapy

Introduction

Allergen specific immunotherapy for treatment of IgE-mediated allergy has been used for longer than a century now; yet, in spite of abundant experience, subcutaneous immunotherapy (SCIT) has not become a widely accepted routine treatment for allergy. Patients will suffer severe symptoms, surgery, and the heightened risk of asthma, polyps, and chronic ill health before even considering immunotherapy. Patients of all ages and especially children find it difficult to adhere to SCIT. Not only is recruitment to immunotherapy poor, with less than 5% of all allergic patients currently receiving immunotherapy, compliance is even poorer: among adult patients who agree to undergo SCIT more than two-thirds shall drop out within a year of initiation, while one-tenth of SCIT candidates fail to even show up for their very first injection. Furthermore, subcutaneous immunotherapy has failed to expand its scope and attract interest in the management of allergic diseases with significant prevalence and chronic nature such as atopic dermatitis. As far as food allergies are concerned, after an initial disappointing approach, SCIT is not even attempted any more. Now, a wealth of evidence in literature and clinical practice supports the safety, efficacy, feasibility, compliance, and economy profile of sublingual immunotherapy (SLIT). The biotechnology industry is persistently pushing for a wider application of SLIT but at the present time practice parameters are lacking. This state is not unique to SLIT: guidelines for SCIT have often been vague and sometimes based on sporadic or biased data. For instance, there have been only 13 studies addressing the efficacy and safety of multiallergen extracts in either form of immunotherapy, SLIT or SCIT, all of them sporadic and of low power. In spite of practically all immunotherapy patients having been or being sensitized to various different allergens and, therefore, being treated with multiallergen extracts, the—already limited and scanty—ongoing research still commits itself to single allergen studies for “monosensitized” patients, thus avoiding the thorny issues of specificity of immunotherapy, new onset allergen sensitization during the course of immunotherapy, allergen interaction, and stability in the patient's formulated extracts mixture. Other issues add to the confusion: double-blind, controlled studies comparing multiallergen SLIT versus SCIT are lacking; the predictive value of adverse reactions during immunotherapy as to its therapeutic outcome has never been raised in specialty literature. Furthermore, most published studies on either SLIT or SCIT are directly or indirectly funded by manufacturers with financial interests in controlling emerging forms of immunotherapy. The pharmaceutical industry is seeking to market mixed immunotherapy extracts as products on industrial scale that could be prescribed without ongoing specialist evaluation, but this attempt does not coincide with optimal (or even ethical) management of chronic diseases characterized by high individualization, ever-changing severity and shifting sensitizations. With these precepts, an evaluation of immunotherapy in general as a concept and practice is mandatory. The merits and risks of immunotherapy have been discussed enough to establish safety and efficacy. A comprehensive theory is needed that would define immunotherapy's prerequisites and targets, delineate its mechanisms, and allow the logical integration of newly erupting scientific and clinical data within the frame of legitimate medical specialization.

Abstract

Allergen specific immunotherapy is the only disease-modifying modality available for allergy. Immunotherapy performed by allergists–immunologists is an effective means to control long-term morbidity and health- related costs for chronic diseases affecting a significant part of the general population. A wealth of new information is now requiring a reassessment of immunotherapy and its practice. In the field of physiology, antigen presentation by dendritic cells has shed new light on our understanding of the mechanisms of immunotherapy. In clinical practice, the sublingual administration of allergens has opened immunotherapy to an array of new applications and is promising to make immunotherapy available to large numbers of patients. The new developments, both scientific and clinical, are reviewed and a number of practical issues are addressed in view of the broadening of the practice of immunotherapy.

Keywords

immunotherapy, sublingual immunotherapy, allergy, food allergy, allergic rhinitis, asthma