The usefulness of component-resolved diagnostics in food allergy.

The gold standard for the diagnosis of IgE-mediated food allergy is an oral food challenge (OFC) that directly verifies the causal relationship between clinical symptoms and offending foods.1 However, OFC carries a risk of developing fatal reactions (such as anaphylaxis) in some patients. A thorough history taking and supportive tests such as a skin prick test (SPT) or serum food-specific IgE (sIgE) levels have been used in clinical practices for the diagnosis of IgE-mediated food allergy. A SPT or serum test can be performed easily and safely in an outpatient clinic setting. However, clinicians must be cautious in interpretation due to the possibility of a false positive or false negative test results. SPT or serum tests also have limitations and cannot replace OFC for the diagnosis of food allergy.2

Component-resolved diagnostics (CRD) is a diagnostic test to detect specific IgE against individual allergen molecules or components using purified native or recombinant allergens.3 It is expected that CRD could provide further diagnostic information in patients with an IgE-mediated food allergy in terms of predicting clinical relevance or prognosis.

The level of specific IgE toward Ara h 2 was correlated with a clinical threshold in patients with a peanut allergy.4 In a study that compared patients with a peanut allergy from 3 countries (Spain, the United States, and Sweden), American patients frequently had IgE against Ara h 1 to 3 that often manifested with severe symptoms, while sensitization to Ara h 9 and Ara h 8 were primarily found in Spanish and Swedish patients, respectively.5 One study that included 37 adults presented the accuracy of a specific IgE antibody toward rPen a 1 for shrimp allergy.6 Yang et al reported that sIgE antibodies to shrimp tropomyosin is more useful than a skin prick test to predict clinically relevant reactions in patients with shrimp allergy.7 An Italian study of egg allergy showed that 94% of Gal d 1 negative patients tolerated boiled egg; however, 95% of Gal d 1 positive patients reacted to raw egg. This study suggests that sIgE against Gal d 1 appears to be a good predictor of egg allergy.8 There have been more studies to report the higher diagnostic value of food allergies such as wheat, soybean, and hazelnut allergies.9-11 Taken together, CRD could be used to predict clinical reactivity in subjects with a sensitization to foods and to establish sensitization patterns with prognostic outcomes.

Cow's milk allergy (CMA) is an adverse reaction to cow's milk protein that is either IgE-mediated or by non-IgE-mediated. Cow's milk proteins acting as allergens consist of casein and whey proteins. The casein fraction (Bos d 8) accounts for 80% of total protein, while 20% is contained in whey proteins such as β-lactalbumin (Bos d 4), β-lactoglobulin (Bos d 5), bovine serum albumin (Bos d 6), immunoglobulin (Bos d 7), and lactoferrin.12 The prevalence of CMA in Western countries ranges from 0.12% to 3.8%, and frequently occurs during infancy.13 CMA is the second most common food allergy in young Asian children13 and is also common in Korean infants with a prevalence of 1.7%.14 Consequently, the accuracy of diagnostic tests and prediction of prognosis in CMA is important.

In the present issue, Cingolani et al. presented the usefulness of CRD to determine the severity of cow's milk allergy.15 The authors compared the level of specific IgE against nBos d 4, nBos d 5, and nBos d 8 between the anaphylaxis group and non-anaphylaxis group in patients with CMA. They found the level of IgE to nBos d 8 can differentiate the "high anaphylaxis-risk" from "milder-risk" group. The results support the usefulness of CRD in food allergy; however, not all studies consistently show the predictive value of CRD. Ott et al, evaluated the commercially available allergen microarray assay using Bos d 4, 5, 6, and 8 in patients with CMA.16 They found that no single allergen was detected to discriminate between asymptomatic sensitization and clinically relevant allergy. With regard to peanut allergy, American patients frequently had sIgE against Ara h 1 to 3 and some tended to present with more severe symptoms.5 Ara h 2 seems to be a good predictor for peanut allergy; however, the outcome of the food challenge could be predicted with sIgE to Ara h 2 only in 50% of the patients.17 Tolerance to baked egg was not predicted by sIgE against ovomucoid.18 CRD is promising as a diagnostic tool in food allergy, but its diagnostic value is limited at this point.

CRD is currently available for the diagnosis and management of food allergy; in addition, it is more important in the clinical investigation of IgE-mediated food allergy compared to conventional methods such as SPT or serum sIgE against whole proteins from allergenic foods. Recently, a number of studies have demonstrated the utility of CRD to predict the presence or severity of food allergy. CRD may be helpful to improve the specificity of current allergy testing; however, it is evident that more clinical studies to validate IgE reactivity are required.