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e-Journal

 

ABC's Of Allergies
(Released August 2006)

 
  by Sujata Suri  

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Contents

1. DNA vaccines
Several types of new allergy treatments are under development. Because they are not proteins and can't translate into proteins to become allergens in allergic persons, DNA vaccines can be used to reduce allergic reactions. DNA vaccines can be developed by one of three approaches: (i) using the naked DNA of allergens (ii) using hypoallergenic derivatives of allergen DNAs by modification of nucleotides; or (iii) fragmenting allergen DNA and fusing with ubiquitin, as fragmenting the antigen destroys its native structure. Based on their Th1-promoting properties, DNA vaccines balance Th2-mediated immune reactions, a quality which renders them a promising alternative for immunotherapy against allergies (Hartl et al. 2003).

2. Anti-IgE antibodies
Binding of IgE antibodies to specific high affinity receptors (called Fc epsilon receptors, or FceRI) on basophils and mast cells triggers the release of histamine and other mediators that result in allergy symptoms. Thus developing anti-IgE antibodies against IgE could be a potential therapeutic option for allergy treatment. Various such antibodies have been developed. An anti-IgE monoclonal antibody termed BSW17 peptide has been synthesized that is nonaphylactogenic, predominantly blocks binding of IgE to FcεRI, recognizes IgE already bound to FceRI, and interferes with the function of IgE-sensitized basophils and mast cells (Rudolf et al. 2000).

Another such humanized monoclonal antibody is Omalizumab, which not only inhibits the binding of IgE to FceRI but also decreases FceRI expression on mast cells and basophils. It also reduces the synthesis of IgE by B plasma cells and thereby attenuates hypersensitivity reactions (Schulman; 2001). Leung et al. (2003) also humanized an IgG1 monoclonal antibody for peanut related allergies called TNX-901 that recognizes and masks an epitope in the IgE responsible for binding to the FceRI on mast cells and basophils. Their results indicate that a dose of 450mg of TNX-901 significantly increases the threshold of sensitivity to peanuts from a level of 178mg (1/2 a peanut) to 2805mg (9 peanuts).

3. Modification of the epitopes
Modification of IgE binding sites, i.e. epitopes of allergens, could be another approach to attenuate hypersensitivity reactions. Epitopes of allergens can be created by modifying allergens and their hypoallergic derivatives. Singh and Bhalla (2003) have demonstrated that the anaphylactic potential of rye grass pollen can be reduced by introducing a few point mutations in their allergens before using them for immunotherapy. In the shrimp allergen tropomycin, eight IgE epitopes were identified and mutated. These mutations had no effect on their secondary structure (in other words, did not change the basic structure of the IgE) but the allergic response was reduced by 90-98%, so this mutant could be helpful for therapy (Reese et al. 2005).

4. Target mast cells and basophil cells expressing FceRI
Another possible option to reduce IgE related hypersensitivity reaction is to directly kill the mast cells and basophils expressing high affinity receptors (FceRI) for IgE. Human originated apoptosis-inducing proteins can be used, as these will be less toxic or less immunogenic than the proteins produced in a different animal or plant. From two human apoptosis-inducing proteins, Bak and Bax, new chimeric proteins termed as Fce-Bak/Bax have been synthesized that induce apoptosis in FceRI-expressing mast cells and basophils (Belostotsky & Galski, 2001).

Also, these chimeric proteins do not degranulate mast cells. In birch pollen allergic people, the degranulation of mast cells releases enzymes such as a-chymase and other serine proteases (Mellon et al. 2002). Interestingly, the chymase cleaved IgE-binding epitopes of profilin giving profilin no chance to react with IgE and thus attenuated mast cell activation. Destruction of IgE binding epitopes of profilin with chymase could further limit pollen allergic reaction in sensitized individuals.

5. Immunotherapy
. Immunotherapy (biologic therapy) is indicated for people who are extremely allergic to specific allergens. Immunotherapy is done by gradually exposing the patient to lower doses of allergens to reduce the sensitization. It relies on the progressive production of the blocking antibody IgG and reduction in excessive production of IgE .

Li et al. (2003) developed a new chimeric peanut protein and co-administered it with adjuvant heat-killed Listeria monocytogenes (HKLM) to mice that were allergic to peanuts. The researchers found that these mice showed lower histamine release and fewer peanut specific IgE antibodies, and that allergic symptoms were reduced. Thus, their results suggest that immunotherapy with peanut protein and HKML could treat peanut allergic patients.

6. Harvesting nature
Aqueous extract of the plant bugleweed (Lycopus lucidus) decreases allergic response by reducing histamine, TNF∝ and interleukin (IL-6) release from mast cells (Tae-Yong et al. 2005). The same effect was reported by using hop, Humulus lupulus, extracts on rat mast cells of rats and human basophilic cells (Takubo et al. 2006).

7. Reducing the allergenicity of food crops
Scientists are trying to develop methods to reduce plant allergenicity. Generally it is believed that environmental stress to plants due to pollution, fertilizers, pesticides, heavy metals, etc., reduces their vitality and makes them produce various defense molecules (Thi and De Blic, 2005); these defense molecules could be active allergens (Uguz et al. 2005). Malkov et al. (2006) have reported that soil treatment with silicate breaking bacteria (Bacillus oligonitrophilus KU-1) in apples and strawberry plants can attenuate plant allergenic potency. The bioavailability of silicon produced by B. oligonitrophilus KU-1 increases the vitality of plants and reduces the production of allergens. So soil treatment with B. oligonitrophilus is a simple and inexpensive method for reducing the allergenic capacity of food crops.

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Special thanks to Deborah Whitman for her invaluable help with this Discovery Guide

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