An allergy diagnosis requires a careful combination of detailed allergy focussed clinical history and appropriate allergy testing. This typically includes skin prick testing or sometimes blood tests. Recently there have been significant advances in allergy blood testing which has resulted in additional information that can be helpful both in terms of diagnosis and also predicting likelihood of severe reactions. These advances generally focus on different component parts of the allergen in question.
What is molecular diagnosis?
Molecular diagnostic techniques are a recent advance in allergy blood testing which allows information to be obtained about different proteins within a particular allergen. A good example would be allergy testing to peanut. Traditional allergy blood testing to peanut looks at the amount of allergic antibody (IgE) produced by the patient’s immune system directed against peanut. The higher this number is on the blood test, the more likely it is that the patient is allergic, but it is not an entirely reliable test as sometimes patients can have high levels but still be fine when they eat peanuts or likewise, some patients who are allergic to peanuts may only have very low levels. There is therefore a need for a more accurate diagnostic test. Molecular diagnostics looks at the amount of IgE produced by the body’s immune system against a range of different component proteins that make up the whole peanut. Subsequent research has shown that raised levels to a particular peanut protein (Ara h 2) are actually a significantly more reliable marker of whether somebody is allergic to peanut than measuring the IgE against the whole peanut.
What is component-resolved diagnostics?
Component-resolved diagnostics is a term that refers to the use of additional data that can be obtained by looking at IgE levels against different component parts of a particular allergen. Hazelnut allergy can commonly take two quite distinct forms; one is referred to as a primary allergy where IgE against certain proteins in hazelnut can lead to severe reactions if the food is accidentally consumed. However, in other cases, a hazelnut allergy can occur because of cross-reactivity with pollen. This is often referred to as Pollen-Food Syndrome where a patient develops hay fever related to, for example birch pollen, and then finds that when they eat raw hazelnut, that they get a tingly reaction in their mouth suggesting that they are allergic to it. However, if a reaction is caused by cross-reactivity, the risk of severe reaction is very low and often the patient can continue to eat hazelnut as long as it is in a processed form whereas with a primary allergy the hazelnut will need to be avoided carefully in every situation. Component-resolved diagnostics uses the data provided by a blood test as to how much IgE is directed at different proteins within the hazelnut. If the levels are very high to the hazelnut specific proteins but not to those that cross-react with pollen, then a diagnosis of primary hazelnut allergy can be made and the patient counselled that they will need to avoid hazelnut carefully in all situations as there is a risk of severe reaction. They may, for example, need to carry adrenaline autoinjectors (EpiPens). However, component-resolved diagnostics may also show that a particular patient has IgE only to the hazelnut proteins that cross-react with pollen and not to any others and therefore together with a confirmatory clinical history can be advised that the risk of reactions is low and no adrenaline autoinjector required.
How does molecular diagnosis testing work?
Molecular diagnostics are done using blood samples. This can either be done using whole blood sent to a laboratory in the same way as traditional allergy blood tests are done or more recently there have been new technologies that allow a very small amount of blood, possibly taken at home using a finger prick sampling method, to be sent to a laboratory for analysis which then provides results on hundreds of different allergen components. Currently, there are two commonly used types – one called an ISAC and another called an ALEX test. These use similar technology and has become a very useful part of clinical practice.
What to expect from a molecular diagnosis test?
The test requires a blood sample usually taken by a traditional blood draw with the results then following a few days later. More recently, tests that require smaller samples have allowed home testing to be carried out, but the sample still needs to be sent to a laboratory with a wait sometimes of 2-3 weeks before the results are returned. The results that are returned can be complex and difficult to understand and therefore it is usually recommended that these results are reviewed by your allergist in a way that is bespoke to the issues that were raised at your consultation. These types of tests can prove very unhelpful if used simply as screening tests without a consultation as like traditional allergy tests they can still return positive results to foods and other items where there is in fact no allergy at all.
Molecular diagnosis testing versus allergy diagnostic testing
Traditional allergen IgE testing (previously known as RAST testing) usually provides details of the amount of IgE detected against particular foods or environmental allergens whereas molecular testing looks at component parts of these allergens to provide more detailed information, which when interpreted correctly and in certain situations can provide useful information about the likelihood of allergy as well as potential severity of reactions.
What allergies does a molecular diagnosis test identify?
Molecular diagnostic techniques can be useful for a range of food allergies, venom allergies and inhalant allergies. In select cases, it can also contribute towards diagnosis of drug allergies, but this is less commonly useful.
What results does molecular diagnosis show?
Molecular diagnostic tests are returned as a level of IgE directed at the components in question. Very broadly speaking, the higher the level is, the more likely there is genuine allergy but this needs to be taken in context with the clinical history and also our understanding of that specific test, as different levels can have a very different meaning in different allergens.
Professor Adam Fox
Date reviewed: March 2022
Adam Fox is a Professor of Paediatric Allergy with over 20 years experience in both the NHS and private sector. Professor Fox is Commercial Medical Director at Guy’s & St Thomas’ Hospitals NHS Foundation Trust and Professor of Paediatric Allergy at King’s College London and the founding Director of the KCL Allergy Academy, a postgraduate educational programme, which was a finalist at the BMJ Awards in 2018.
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