History and Utility of Specific IgE Cutoff Levels: What is the Relevance for Allergy Diagnosis?

Allergy is defined clinically, by symptoms on allergen exposure. A patient is considered sensitized when allergen-specific IgE (sIgE) antibody can be detected in serum or plasma or a skin test result is positive, even if no clinical reaction has been experienced. Sensitization should be regarded as a requisite and risk factor for allergy but is not synonymous with an allergy diagnosis. To provide a correct allergy diagnosis, test results regarding allergen-sIgE must always be considered in view of the patient's case history and clinical observations. Correct assessment of a patient's sensitization to specific allergens relies on the use of accurate and quantitative methods for detection of sIgE antibodies. The evolution of sIgE immunoassays toward higher analytical performance and the use of different cutoff levels in the interpretation of test results sometimes cause confusion. Earlier versions of sIgE assays offered a limit of quantitation of 0.35 kilounits of sIgE per liter (kUA/L), which also became an established cutoff level for a positive test result in the clinical use of the assays. Current sIgE assays are capable of reliably measuring sIgE levels as low as 0.1 kUA/L and can thereby demonstrate sensitization in cases in which previous assays could not. When the outcome of sIgE test results is evaluated, it is critically important to distinguish between the analytical data as such and their clinical interpretation. Even though sIgE may be present in the absence of symptoms of allergy, available information suggests that sIgE concentrations between 0.1 kUA/L and 0.35 kUA/L may be clinically relevant in some individuals, not least among children, although this should be further evaluated for various allergies. Moreover, it is becoming widely adopted that nondichotomous interpretation of sIgE levels may offer a diagnostic benefit compared with using a predefined cutoff level.(c) 2023 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2023;11:3021-9)