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Food Allergy

Foods are an important cause of allergic reactions including fatal anaphylaxis. Severe reactions to foods can occur at all ages, from infants receiving cow's milk or casein or whey hydrolysate formulas to children, adolescents, and adults. Although some reactions caused by formula proteins in infants may decrease in intensity with age, the risk for severe reactions to other foods persists for long periods of time, even in absence of exposure. Severe reactions have been associated with fish, shellfish, nuts and seeds, legumes, celery, and to a lesser extent with grains, milk, and eggs food allergy, milk allergy, alergy, alergic

IMMUNOTHERAPY

Immunotherapy of IgE-mediated diseases has a high incidence of untoward reactions; therefore, alternative methods are being developed to reduce the risk-to-benefit ratio in the treatment of allergic disease. Although these methods are being developed primarily for use in the treatment of inhalant allergies, some

Pharmacologic therapies for the treatment of respiratory allergic disease have markedly improved in the last decade, but treatment for food allergy remains strict avoidance and symptomatic relief of systemic reactions with antihistamines, vasoconstrictors, and volume expanders. Novel immunotherapy methods that are currently being developed and studied for IgE-mediated disease suggest promise for effective and safe future therapies. The methods currently being tested include oral, immune complex, and peptide immunotherapy, as well as anti-IgE therapy and DNA vaccine therapy.

TABLE 1 -- EMERGING IMMUNOTHERAPY METHODS
Therapy Route Mechanism Safety
Oral immunotherapy Oral Tolerance Appears safe
Immune complex therapy Intradermal Unknown Appears safe
Peptide immunotherapy Subcutaneous/oral Diminish T-cell reactivity Appears safe
Anti-IgE Intravenous/subcutaneous Deplete allergen-specific IgE Appears safe
DNA immunization Subcutaneous Switch Th2 to Th1 response Unknown
 

Oral Immunotherapy

Oral immunotherapy with large doses of allergen has been shown to induce immunologic tolerance in animal models,  but studies in humans have shown mixed results in efficacy. These studies have been performed in patients with respiratory allergy associated with pollens. Taudorf et al demonstrate a beneficial clinical effect of oral immunotherapy in birch pollen-allergic patients during birch pollinosis. Eye symptom scores and conjunctival sensitivity by conjunctival provocation

More recently, Van Deusen et al  reported clinical efficacy and safety of oral immunotherapy with a new oral delivery system. A serologic response similar to that seen in conventional subcutaneous injection immunotherapy in the treatment group and increases in short ragweed-specific serum IgG and IgG4 were noted; no

The findings in these two double-blind, placebo-controlled studies suggest that oral immunotherapy is safe, well tolerated, and may be effective clinically. Future studies with higher doses or longer duration may prove beneficial as clinical and serologic parameters suggest immunologic alteration that has been associated with

Immune Complex Therapy

Immune complex therapy using autologous immune complexes has also been investigated. Machiels et al studied the effects of antigen-antibody complex therapy for the treatment of immediate-type hypersensitivity disease. Patients suffering from allergic rhinitis and asthma associated with exposure to grass pollen were injected intradermally with antigen-antibody complexes prepared from grass pollen allergens and autologous-specific antibodies isolated from the sera of grass pollen-allergic patients. This form of therapy improves nasal and bronchial asthma symptom scores, and clinical benefit is achieved within weeks of treatment. In addition, this treatment prevents the expected seasonal rise in specific IgE antibodies without increasing specific IgG antibodies. Although many of these measures were generally subjective, there were statistically significant differences when compared with the placebo group, and this form of therapy appeared to be safe. In a second study, asthmatics with sensitivity to the house dust mite Dermatophagoides pteronyssinus were treated with antigen-antibody complexes prepared from dust mite allergen and dust mite-specific IgG. After immunotherapy by the immune complex method, bronchial and skin reactivity to D. pteronyssinus were

Peptide Immunotherapy

Peptide immunotherapy employs subcutaneous injection therapy with peptide fragments containing the allergenic epitope, rather than the complete protein, making the cross-linking of IgE molecules on the surface of mast cells and basophils unlikely. This form of immunotherapy would theoretically minimize the possibility of

The above novel approaches to the treatment of allergic disease have been allergen-specific, making treatment of multiple allergies potentially complicated. In allergic disease, a less specific form of therapy that could dampen or eliminate the allergic hypersensitivity state would be more desirable. Casale et al studied the

DNA Immunization

DNA immunization is another novel approach under study for the treatment of allergic disease. It was recently shown that naked plasmid DNA (pDNA) encoding an antigen is taken up in vivo by antigen-presenting cells; it is suggested that an endogenously produced protein or peptide fragment is then presented on the 

Novel approaches to therapy for allergic diseases are only in their infancy; more detailed investigations are required to better define the risk of adverse reactions, the duration of treatment effects, and the doses that will be tolerated or required for an appropriate long-lasting immunologic response. Peptide immunotherapy,

Peptide immunotherapy, anti-IgE therapy, and DNA vaccines have been studied using subcutaneous injection, like traditional immunotherapy. Immune complex therapy has been administered intradermally. The oral route of allergen therapy had been largely unsuccessful until recently. The reason is believed to be related to

MUCOSAL VACCINES

In the absence of clearly defined molecular and cellular mechanisms that mediate allergic reactions in the gut, it is difficult to speculate as to the most effective immunotherapeutic interventions. There are several possible therapeutic interventions that might prove successful for treatment of food allergies. First, it may be possible to preferentially increase the amount of secretory IgA and systemic specific IgG against a particular allergen using certain oral immunization regimens.

A second possible mode of immunization that might have therapeutic value involves the presentation of allergen in a vaccine delivery vector. For example, by expressing an immunogen in an attenuated bacterial strain with affinity for invading the gut, it is possible to mount an enhanced mucosal and systemic immune

The gut-associated lymphoid tissue is unique in that most immunogens that are presented in this compartment result in tolerance. The mechanisms responsible for this suppression are still being defined; however, the delivery of immunogens at this site has been utilized as a method for inducing local and systemic tolerance, especially for altering autoimmune diseases. Upon oral inoculation with high doses of immunogen, reduced immune responses to these immunogens have been

There are a variety of other possible oral therapies that may prove useful in the treatment of food allergies in addition to the ones noted previously. Each therapy has its limitations, however, and it is not possible to predict the efficacy of any one such treatment presently. A more thorough characterization of the cellular and molecular mechanisms responsible for stimulation of allergic reactions at mucosal surfaces would contribute greatly to an understanding of which therapies might be most successful. In the final analysis, however, efficacy of oral immunotherapies must be evaluated using appropriate model systems or using clinical trials.

DEVELOPMENT OF HYPOALLERGENIC FOODS THROUGH BIOTECHNOLOGY

Ideally, the preferred treatment for food-allergic individuals is avoidance of exposure to the food that stimulates an allergic reaction. Avoidance is not always possible, however, particularly as new foods are developed that may contain proteins of unique or exotic origin. Indeed, the manipulation of plants through biotechnology has yielded a number of transgenic crops that are resistant to chemical herbicides and insect pests and have enhanced nutritional quality, increased

As discussed previously, the preferred treatment for food-allergic individuals, if avoidance is not possible, is the development of hypoallergenic foods with reduced or no allergen content that allergy patients can tolerate. In the past, physical and chemical treatments (i.e., the chemical or enzymatic hydrolysis of proteins such as those present in milk or rice) have been used to reduce allergen content. Based on genetic engineering, however, it may now be possible to suppress or delete the gene coding for a particular allergen or induce more subtle changes by altering allergen protein structure resulting in a food with little or no

The overall objective is to produce a food that either no longer contains the offending allergen(s) or whose proteins have been modified in such a way so that they are no longer allergenic. The chances for success of this approach are greatest for foods that contain a limited number of major allergens. The allergens in any

Gene suppression is a method to suppress the translation of the gene into protein. Antisense DNA technology has been applied to suppression of a major rice allergen. This method reduces the levels of specific allergens in a food by the introduction of genes in the antisense (opposite direction required to produce a