Allergen immunotherapy (ITA), otherwise known as desensitisation, is a treatment for allergic diseases. In brief, it involves the regular administration of an allergen in small doses so that the body gradually becomes used to it. In this way, allergy symptoms are reduced or disappear. It also helps patients reduce the use of medication and improves quality of life [1].
What tests prior to allergen immunotherapy?
The efficacy of ITA depends largely on the selection of an appropriate allergen vaccine containing the allergen responsible for the patient’s symptoms. Therefore, it is extremely important to identify precisely what sensitises the patient in order to select the most appropriate allergen for desensitisation [2]. To achieve this, before qualifying for ITA, tests are performed to confirm the presence of specific IgE antibodies (sIgE), the very antibodies that are responsible for allergic reactions.
These tests include skin tests as well as blood tests. The first involve applying a small amount of an allergen usually to the patient’s forearm and then pricking to assess the skin’s reaction to this allergen. Blood tests assess sIgE concentrations against whole allergens or individual allergen proteins (molecular diagnostics of allergy – DMA) [3].
Molecular tests are more precise than traditional skin tests
Skin tests and traditional blood tests assess sIgE against whole allergens, so-called allergen extracts. These extracts are mixtures of multiple allergenic and non-allergenic proteins. Molecular diagnostics, on the other hand, allows the determination of sIgE antibodies directed against specific proteins (allergenic components). Why is this so important? First of all, because on this basis it is possible to determine the allergen with high probability, assess the validity of the patient’s eligibility for ITA and predict the chance of success of immunotherapy [2]. Furthermore, with the help of such diagnostics, we can indicate cross-reactions between different allergens.
For which allergens prior to allergen immunotherapy is such diagnostics available?
Immunotherapy is used primarily for inhalant allergies and allergies to hymenopterous insect venoms. The most common inhalant allergens are pollen and house dust mites. Available molecular tests allow the determination of sIgE against molecules such as:
- birch pollen (Bet v),
- timothy (Phl p),
- mugwort (Art v),
- house dust mites of the species Dermatophagoides pteronyssinus and farinae (Der p and Der f),
- the mould Alternaria alternata (Alt a).
Molecular diagnostics is also used in ITA with hymenopterous insect venoms. It allows the determination of sIgE against bee (Api m) and wasp (Ves v) venom molecules [1].
Advantages of molecular diagnostics in qualifying for immunotherapy
Component diagnostics provide both the doctor and the patient with valuable information that can help in the decision to qualify for ITA. In contrast, traditional diagnostic methods used in qualifying for immunotherapy do not allow the determination of which of the allergens causing the positive extract tests is the source of the primary sensitisation and which is the result of a cross-reaction. As a result, misinterpretation of the result and selection of an inappropriate desensitisation preparation may occur. This, in turn, will result in failure of ITA [4].
In contrast, based on the result of the molecular test, the doctor can assess the appropriateness of starting immunotherapy and tailor it to the individual needs of the patient. This approach:
- increases the efficacy and safety of the treatment,
- makes it easier for the patient to decide whether to start treatment [2].
Studies indicate that the use of DMA can influence the change of desensitisation preparation in up to 50% of cases [5].
Sensitisation to one allergen versus reactions to other allergens
A unique feature of molecular diagnostics is its ability to distinguish primary sensitisation from cross-reactions. Among allergenic proteins, we distinguish between specific allergens, which are found in a specific allergenic source, and panallergens (profilins and polcalcins), which are widely distributed in nature and show a high degree of similarity in structure. These molecules can cross-react, leading to positive skin tests and sIgE determinations with allergen extracts. For example, people with birch pollen allergy may get a result suggestive of grass pollen allergy.
Without the use of DMA, it is impossible to determine which symptoms are the result of primary sensitisation and which are related to cross-reactions. This is extremely important for the effectiveness of immunotherapy. Why? Because if an ITA with meadow thyme allergen is applied to a person originally sensitised to birch pollen with a cross-reaction to grass pollen, the efficacy of such therapy may be very low or nonexistent. ITA with birch pollen will be of much greater benefit in such a case [3,4,6].
Molecular tests are available in the whole Poland
At present, molecular diagnostics of allergy is widely available and can be performed in most laboratories in Poland. Among the tests available, we can distinguish those that enable the determination of sIgE for a specific protein, e.g. Bet v 1 of birch, or several most relevant molecules from a single allergenic source, e.g. Der p 1, Der p 2, Der p 10 and Der p 23 of Dermatophagoides pteronyssinus mites, or Api m 1, Api m 10, Ves v 1 and Ves v 5 of bees and wasps.
It is also possible to perform multiplex tests, where almost 180 proteins, the most relevant of all available allergens, are determined. Such tests are particularly indicated in diagnostically doubtful cases or in situations of anaphylaxis of unknown cause [6].
Are there any contraindications to performing a molecular test?
One of the biggest advantages of molecular tests is that there are practically no counter-indications to performing them. They can be used regardless of the patient’s age, and there is no need to discontinue allergy medication, as is the case with skin testing. In addition, molecular tests do not carry the risk of severe allergic reactions or other side effects [7].
Which allergen molecules are associated with successful immunotherapy?
It has been shown that sensitisation to specific molecules can influence the greater probability of successful immunotherapy. The chance of successful immunotherapy is associated with the presence of sIgE against the major allergens of a given allergen source (table). These include Bet v 1 of birch trees or Der p 1 and/or 2 of house dust mites. The presence of sIgE against the major allergens helps qualify the patient for immunotherapy with the appropriate allergen [6].
What allergen molecules are associated with ineffective ITA?
We can also distinguish molecules to which sensitisation is usually associated with low ITA efficacy. These include profilins or polcalcins, which are widely distributed in the plant world. Hence, the finding of sIgE against these proteins alone in a patient is not an indication for immunotherapy.
The co-occurrence of sensitisation to panallergens and major allergens has also been shown to reduce the chance of successful ITA. The low efficacy of immunotherapy may in some cases also be due to insufficient sensitising protein in the allergen vaccine, such as in the case of the major house dust mite allergen Der p 23 or bee venom Api m 10 [6]. The most important major allergens and panallergens relevant for qualification for immunotherapy are shown in the table.
| The most important allergen molecules relevant to qualification for immunotherapy [2,6] | |
| Allergens associated with clinically effective ITA | Allergens that are not an indication for ITA |
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Do European standards require molecular diagnosis before immunotherapy?
The current European Academy of Allergy, Asthma and Clinical Immunology standards for specific immunotherapy emphasise that the basis for patient eligibility for ITA is proof of an association between allergen exposure and the presence of IgE allergy symptoms [8]. Current European standards do not require an absolute molecular diagnosis in the qualification for immunotherapy. However, they emphasise the increasing importance of DMA in the qualification for ITA, especially in diagnostically doubtful cases, e.g. in patients with allergies to several allergens [2].
Is it worth using DMA in qualifying for allergen immunotherapy?
Although not currently required before starting ITA, DMA tests provide a lot of valuable information. They not only help to identify the allergens responsible for symptoms, but also to predict the efficacy of immunotherapy. Based on the patient’s sensitisation profile, cross-reactions can be distinguished from primary sensitisation and the protein responsible for the allergic symptoms can be precisely identified. This allows the selection of an appropriate desensitisation preparation and a faster decision on desensitisation, thereby increasing the chance of treatment success.
