Diagnostics Allergy


from allergenic sources. Variability in extract quality can greatly affect results. Many allergens are heat labile or degrade easily and may not maintain their native conformation, which can decrease sensitivity. Specificity may be reduced by contaminants in the extract, such as pesticides or even fungi or bacteria growing on vegetables or pollens. Added to this, organisms are composed of thousands of different types of proteins and glycoproteins, only a fraction of which have been positively identified as being allergenic. Then too, an allergic individual may react to all or only some of the allergenic protein species.


The introduction of molecular biology techniques to the study of allergic disease has contributed greatly to the identification and understanding of these allergenic proteins. Based on cDNA sequencing and 3D structure analysis, most allergens have been grouped into a limited number of structural protein families independent of their biological sources. The structural similarities among the various proteins accounts for their subsequent immunological cross-reactions.36


Significant scientific advances and new perspectives in IVTs allows for detailed analysis of IgE specificity to the individual proteins that are responsible for the allergic response.36


In order to diagnose allergy at


Due to allergen cross-reactivity, patients may generate IgE antibodies to a particular sensitizing allergen; at the same time, a patient may demonstrate similar allergic reactions to many taxonomically or biochemically related allergens.


the protein level, serum sIgE tests have been introduced using purified natural or recombinant single allergenic proteins or carbohydrate moieties.36–38


Allergen cross-reactivity occurs because IgE antibodies recognize antigenic determinants that are shared among a variety of allergenic sources (pollens, mites, molds, animal proteins, venoms and foods).36,39,40 For example, in the case of pollen-food syndrome, patients sensitized to birch pollen frequently experience allergic symptoms upon first ingestion of other plant species (grains, vegetables, fruits, and nuts). These symptoms typically include itching, tingling, or swelling of the mouth and/or lips and are termed oral allergy syndrome (OAS). For many of these patients, IVTs using specific antigens rather than whole extracts can accurately measure IgE specific for the molecular allergenic proteins responsible for the oral allergy symptoms associated with pollen-food syndrome.


The best characterized allergen that has been found to be associated with pollen-food syndrome and OAS is Bet v 1, a member of the pathogenesis-related (PR-10) family of proteins. These molecules are heat labile and, as with other heat-labile allergens, generally evoke only mild, localized symptoms.36


More than 95% of birch-pollen-allergic patients have IgE reactive to Bet v 1; however, more than 60% are exclusively sensitized to the Bet v 1 molecule in birch pollen and not to other allergens contained in fruits and vegetables. Additionally, many patients with OAS have sIgE to PR-10 proteins that are highly homologous to Bet v 1, such as Pru


74


The use of molecular allergens in component-resolved diagnosis, where clustering of allergenic source reactivity is determined, rather than traditional testing using whole-extract allergens can aid in identification of the sensitizing agent and ultimately to improvement in the treatment of patients. As an example of this, Asarnoj et al.45


found that Swedish


children with peanut allergy preceded by birch allergy had sIgE to both Bet v 1 and Ara h 8, but had only mild reactions to peanuts. Since Ara h 8 is in the PR-10 family of proteins, it is likely that these children will never develop severe symptoms to peanuts and may not need to practice strict avoidance.


On the other hand, children reactive to Ara h 2 experienced significant reactions to peanuts. Those who were sensitized to Ara h 2 and either Ara h 1, Ara h 3, or both Ara h 1 and h 3, had the worst symptoms and were at the greatest risk for anaphylaxis (Ara h 9 has also been shown to confer similar risk in Mediteranean populations).45


Since Ara h 2


shares common epitopes with almonds and brazil nuts, this can explain why some children with a peanut allergy are also sensitive to these tree nuts, while children who are not sensitized to Ara h 2 are not.28


Conclusion


Since the primary care physician or pediatrician is likely to be the first practitioner to evaluate possible allergy, IVT provides a convenient, reproducible and reliable tool that does not require extensive training for interpretation. Component testing is likely to contribute to better specificity with respect to identifying the exact allergens responsible for clinical reactions, although it may offer more complexity in interpretation. Once the likelihood of allergy has been established, the primary care practitioner can determine whether referral to an allergist is appropriate for further testing, refinement of diagnosis and specific immunotherapy.46


n US RESPIRATORY DISEASE


Those allergenic proteins in a source recognized by more than 50% of allergic patients are termed major allergens. Minor allergenic proteins are of less importance and are recognized less frequently by sensitized patients.35


av 1 from cherry and Mal d 1 from apple. Specific immunotherapy against Bet v1 based on this knowledge has been shown to reduce fruit-induced OAS.41


Profilins are highly cross-reactive allergens called pan-allergens. IgE from sensitized patients demonstrates extensive cross-reactivity with profilin from botanically unrelated plant sources (trees, weeds, grasses) and plant-derived food allergens (fruits, nuts, vegetables). Patients with IgE to profilin are either sensitized or at risk for developing allergic reactions to various plant pollens or plant-derived foods. Two examples of profilin allergens are Bet v 2, a minor allergen in birch pollen, and Pru av 4 from cherry. Like Bet v 1, IgE to profilins is associated with mild OAS symptoms.36


It is known that IgE reactivity to a specific protein can be associated with varying severity of symptoms. For example, IgE reactivity to PR-10 proteins such as Bet v 1 or to the pan-allergen profilin usually only evokes mild symptoms, such as local edema. However, the presence of IgE to allergens from the PR-14 family (lipid transfer proteins) can lead to severe systemic reactions, such as wheezing, vomiting, pharyngeal edema and anaphylaxis.36,42–44


These proteins are generally resistant to


degradation by heat or digestion. They are associated with food allergy not preceded by pollen sensitization. Major food allergens in this category include Pru p 3 (peach), Pru av 3 (cherry), and Ara h 9 (peanut).36


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