SELECTED ARTICLES FROM THE RECENT LITERATURE 2003

12/29/03

Progress in new approaches to allergy immunotherapy

Summary
A potential limitation to standard allergy immunotherapy (IT) is the possible triggering of systemic allergic reactions, particularly anaphylactic reactions, when allergenic proteins are injected into allergen-sensitive patients. Another limitation for the use allergens such as the major dust mite allergen Der p 1 in IT is that it is a cysteine protease with catalytic properties that may render the effects of IT unpredictable. A way to by-pass these linitations would be to use a DNA immunization protocol in which the injected person would receive injections of DNA encoding enzymatically inactive forms of Der p 1. Wolfowicz et al of the National Univ of Singapore have found that a preparation of Der p 1 DNA, manipulated to include a substituted leader sequence induced a predominantly Th1-type immune response in mice (1). This has the advantage of avoiding a Th2-mediated transient further sensitization of the injected individual, a common occurrence in traditional IT using the allergenic proteins themselves.

In another approach. Wang et al of the United Biomedical Corp set out to induce anti-IgE antibodies that would block mediator release that followed exposure of sensitized subjects to the relevant allergen. They were able to accomplish this by injecting mice with peptides that correspond to epsilon domain #3 of human IgE (2). Thus, the individual may exhibit the same effects as currently induced by the injection of therapeutic anti-IgE preparations now in clinical use.

Reference
1. Vaccine 2003;21:1195-1204;
2. Vaccine 2003;21:1580-1590

Editor's Comments
These findings in mice are encouraging but concerns persist. In the first approach, we do not know how persistent the DNA-induced responses will be. In other attempts at substituting DNA encoding proteins for the protein itself as in IT, the host immune responses were often insufficient or transient. Also, one has to consider the potential for inducing anti-ds DNA antibodies (although injected ds DNA is generally a weak stimulus of formation of anti-ds DNA antibodies). Likewise, one must be sure that induction of anti-IgE antibodies does not lead to pathogenic autoimmune responses. For example, anti-IgE antibodies have been found in a small minority of patients with chronic idiopathic urticaria and in atopic dermatitis as well. Auto immune pathogenic reactivity has not yet been observed in those treated with omalizamab, a humanized monoclonal anti-IgE antibody.

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