A New Diagnostic Test for Peanut Allergy

A new method for diagnosing peanut allergy was outlined in a letter published last month in the Journal of Allergy and Clinical Immunology (JACI). This mast cell activation test was compared to other available diagnostic tests on the basis of sensitivity (the rate of true positive tests, in which a disease is successfully identified) and specificity(the rate of true negative tests, in which a disease that isn’t present is successfully ruled out).

Each test currently used to diagnose peanut allergy has some drawbacks:

• Skin prick tests (SPTs) introduce food allergens just below the skin surface and measure the size of any resulting skin reaction (wheal). SPTs have a low rate of false negatives results that fail to identify a true allergy. However, SPTs have a high false positive rate, failing to distinguish between peanut allergy (in which individuals react to eating peanut-containing foods) and peanut sensitization (in which individuals produce IgE antibodies against peanut protein but may not react to eating peanut).
• Blood tests that measure peanut-specific IgE antibodies in blood serum (fluid) also have a high false positive rate. In contrast, blood tests that measure IgE antibodies against Ara h 2, a commonly allergenic peanut protein, result in fewer false positives but can yield false negatives, because not all peanut-allergic individuals react to Ara h 2.
• A less common and more complicated blood test, the basophil activation test (BAT), assesses whether exposure to food extract can stimulate basophils – a type of white blood cell – to produce proteins associated with allergic reaction. While BATs are better than SPTs and peanut-specific IgE tests at distinguishing peanut allergy from peanut sensitization, basophil testing requires fresh blood and cannot be performed on stored samples. In addition, a significant fraction of individuals have non-reactive basophils that give inconclusive BAT results.
• During oral food challenges (OFCs), an individual eats increasing doses of peanut protein under medical supervision and is assessed for reaction. The current gold standard for peanut allergy diagnosis is the double-blind, placebo-controlled OFC, in which neither the medical professional nor the patient knows whether the patient is eating peanut protein or placebo. The results of an open food challenge, in which patients know they are eating their possible allergen, can be influenced by a patient’s nervousness, because stress symptoms can mimic some symptoms of allergic reaction. OFCs are time-consuming compared to blood tests and can result in reaction symptoms, which are usually mild and receive prompt treatment.

Developed by researchers at King’s College London, the new test described in the JACI letter is based on the activation of mast cells, which are similar to basophils and play a key role in allergic reactions. IgE antibodies bind to the surfaces of mast cells. When these antibodies also bind to their specific allergen, the mast cell releases histamine and other molecules, resulting in the symptoms of allergic reaction.

This mast cell activation test (MAT) assesses the extent to which peanut-treated serum from patients’ blood samples can trigger allergy-associated changes in commercially available cultured mast cells. Like the BAT, the MAT is more effective than skin prick or peanut-specific IgE blood tests in differentiating peanut sensitization and peanut allergy. While the BAT is more accurate than the MAT in diagnosing true cases of peanut allergy, the MAT is more convenient because it uses stored blood samples rather than fresh. The MAT also provides results for patients whose basophils do not respond to the BAT.

The JACI letter noted that mast cell activation by patient serum may function as a biomarker to identify patients at greater risk of severe reaction during a food challenge. The letter also observes that the MAT may find a future role in the monitoring of patients during immunotherapy to follow changes in antibody function that influence the ability of food-specific IgE antibodies to activate mast cells and trigger food allergy symptoms. Tracking the effects of immunotherapy has the potential to help researchers and clinicians predict treatment outcomes and identify distinct subtypes of peanut allergy, enabling them to tailor food allergy care for individual patients.