Accurate diagnosis of allergy requires careful clinical assessment and demonstration of allergen sensitisation, defined as presence of IgE antibodies targeting allergen components (antigens). The main methods used to establish sensitisation are skin prick testing (SPT) and serological testing. SPT is generally only performed by specialist allergists/immunologists, but serological testing can be requested by all clinicians.
& Immunopathologist, Osborne Park
Historically, the radioallergo-absorbent test (RAST) was the predominant serological method. This has now been superseded by a similar method known as serum specific IgE (sIgE) testing. Nevertheless, the terms ‘RAST’ and ‘sIgE’ are still often used interchangeably.
In sIgE testing, patient serum is incubated in a small ‘cap’ containing antigens representative of the allergen in question, typically derived from whole allergen extracts. IgE antibodies targeting any of these antigens will be bound. The amount of IgE binding is then determined and reported quantitatively.
Sensitisation can occur in the absence of a clinical syndrome of allergy, so sIgE results must be interpreted in the clinical context. Screening patients with low pre-test probability for allergy is generally not useful, as positive results are more likely to be clinical ‘false positives’.
Although a stronger positive sIgE result increases the likelihood of the patient having a clinically significant allergy, it does not reliably correlate with severity of the allergy; assessment of severity, and thus indication for carriage of adrenaline autoinjectors, is based on the clinical history.
When a patient tests positive to an allergen via standard sIgE testing, it is not possible to know which of the many antigens contained within the ‘cap’ the patient has IgE antibodies directed towards. It is helpful to appreciate this concept, as not all antigens have equal clinical significance. In fact, patients with significant allergies to certain exposures may be reliably sensitised to only a few specific antigens of interest. Furthermore, some antigens show substantial cross-reactivity with other allergens, a common cause of ‘false positive’ results.
For example, grass pollens contain proteins also common to many plant-based foods, causing some pollen allergic patients to also show positive sIgE results to certain foods. Many of these cross-reactive proteins are labile, meaning they do not survive cooking or digestion, thus not precipitating systemic allergic reactions when ingested. Therefore, although the food sIgE result is positive, the patient is not clinically allergic.
Recognition of this phenomenon has led to development of ‘component resolved diagnostics’, where sIgE testing is directed towards individual allergen components. For example, most patients with peanut anaphylaxis will be sensitised to the peanut protein Ara h 2. Thus, testing for sIgE towards Ara h 2 specifically can aid in determining whether a patient with positive peanut sIgE is more or less likely to tolerate a peanut challenge or be at ongoing risk of anaphylaxis.
Investigation of venom allergy is another example where component resolved diagnostics can assist management. Bee and wasp venoms contain several cross-reactive components, most notably cross-reactive carbohydrate determinants (CCDs). Therefore, some patients have positive sIgE tests towards both bee and wasp venom despite being clinically allergic to only one species. In this situation, sIgE testing towards species specific proteins – e.g. Api m 1 for bee venom – can determine the primary allergy and thus ensure prescription of appropriate desensitisation therapy.
Component-resolved diagnostic testing is more expensive than standard sIgE testing, so laboratories may only accept requests by specialists. Nevertheless, it is rarely required upfront, being most often used as an add-on test to resolve situations with suspected cross-reactivity or to further risk stratify.
Although sIgE testing has utility for investigation of various allergy syndromes, it is not appropriate for all forms of hypersensitivity. In delayed hypersensitivity reactions (which are non-IgE-mediated), skin/patch testing is typically required.
sIgE testing is available for many aeroallergens and foods, but only for a limited number of drugs, many of which have poor sensitivity. Skin testing is required for most drug allergy cases.
Serum sIgE testing is a powerful clinical tool when utilised appropriately, although test selection and interpretation can be challenging, particularly if assay limitations are not appreciated. Immunopathologists can provide advice. Nevertheless, some allergies still require specialist assessment to facilitate skin testing and, in some cases, an observed challenge, the latter of which remains the gold standard for allergy diagnosis.
Key messages
- Positive serum specific IgE (sIgE) results can occur in the absence of clinical allergy. Interpret results in light of the clinical presentation
- A stronger positive sIgE result increases the likelihood of a clinically significant allergy but does not reliably correlate with allergy severity
- Serum sIgE testing is not appropriate for all forms of allergy/hypersensitivity; specialist assessment with skin testing may still be required, particularly for drug allergies.
Author competing interests – nil