Despite improved diagnostic approaches, clinicians still face challenges with diagnosing peanut allergy due to discrepancies between the detection of peanut specific IgE (sIgE) and clinical peanut allergy. Many children are still assessed for possible peanut allergy using an oral food challenge, according to Alexandra F. Santos, MD, MSc, PhD, suggesting that some children have an ambiguous diagnosis following the patient workup and results from skin prick tests and/or sIgE assays.
The ability to detect allergen component sIgE, such as Ara h 2 sIgE and Ara h 6 sIgE—both of which have high sensitivity and specificity—has enhanced how peanut allergy is diagnosed. Increasingly, molecular allergen component arrays, such as the ImmunoCAP immuno solid-phase allergen chip (ISAC), are also being used to help diagnose peanut allergy, because they are sensitive to multiple allergen components that can be measured simultaneously.
Building on Previous Research
Previously, Dr. Santos and colleagues demonstrated that functional characteristics of IgE were important in determining basophil and mast cell activation in response to allergens in a peanut allergy. The functional characteristics included specificity, avidity, and diversity. Basophil and mast cell activation tests had high specificity to diagnose peanut allergy, but these tests require flow cytometry and fresh blood samples.
For a study published in the Journal of Allergy and Clinical Immunology: In Practice, Dr. Santos and colleagues sought to improve the diagnostic utility of serology for peanut allergy by mapping interactions of sIgE to multiple components and IgE functional characteristics. Peanut IgE serology is an automated and standardized test that is accessible in most centers. For the study, the investigators built diagnostic models of allergen sIgE to specific molecules. Four diagnostic models were created:
- Model 1: used 112 allergen components of an ISAC microarray
- Model 2: used six peanut allergen components of the ISAC microarray
- Model 3: used four peanut allergen components of singleplex ImmunoCAP
- Model 4: used functional characteristics of IgE
Combined Approach Improves Diagnostic Accuracy
According to the findings, combining sIgE to various peanut allergens or combining functional characteristics of IgE improved the diagnostic accuracy of individual component sIgE or peanut-specific IgE levels, respectively. Modesl 1 and 3 had the highest accuracy to diagnose peanut allergy, with an area under the curve (AUC) of 0.92. Model 2 had an AUC of 0.86, whereas Model 4 had an AUC of 0.89. Model 3 offered the highest predictive value and the second highest overall diagnostic accuracy.
Notably, Ara h 2 sIgE and Ara h 6 sIgE were confirmed as the most discriminative serologic markers when used in isolation. Combining the major components of Ara h 1, 2, 3, and 6 was superior to use of the markers individually. Similarly, combining the functional characteristics of IgE was superior to using the levels of peanut sIgE alone. “These diagnostic models can be applied in real time during clinical consultations using online calculators,” adds Dr. Santos.
To support clinical decision making, an optimal cutoff was defined for each model. A comparison of the models showed that Model 1 had the highest accuracy overall, followed by Model 3 (Table). “However, Model 3 had the highest specificity and positive predictive value, which is desired for component testing because it allows for confirmation of peanut allergy in patients sensitized to peanut,” Dr. Santos says. Model 3 was also the least expensive test to perform, giving this model an additional advantage.
Taking the Next Step to Optimize Diagnostic Performance
The study confirms that high specificity and sensitivity are key performance characteristics for additional tests in peanut allergy, says Dr. Santos. “Basophil and mast cell activation tests have higher accuracy and higher positive predictive values, but these tests require fresh blood and/or flow cytometry,” she says. “Since these tests are not widely available, they can be more difficult to perform than IgE testing. Combining serologic markers is a good alternative if these resources are available.”