After this module, participants will be able to:
- Describe the difference between marker allergens and panallergens.
- Describe how component-resolved diagnostics can be used to aid the diagnosis of tree pollen allergy.
Tree pollen allergy in the UK
- Grass and birch pollen are the two major causes of seasonal allergic rhinitis in the UK.1
- The most common species of birch in the UK are:1
- Downy birch (Betula pubescens) – most abundant in Scotland and North West England
- Silver birch (Betula pendula/ Betula verrucosa) – most common in South and South East England
- Birch trees belong to the Betulaceae family within the Fagales order. Other Betulaceae tree pollens (alder, hazel, hornbeam and hophornbeam) and pollens from the Fagaceae family (including beech, chestnut, oak) can cross-react with birch pollen due to molecular similarities of the birch homologous group (belonging to the PR-10 protein family).2,3
- Different pollination periods of these trees and the high cross-reactivity of the birch homologous group mean that patients can experience symptoms outside of the birch flowering season of March to May. It is likely that flowering seasons of the other trees before and after the birch season can lead to patients experiencing 2–3 months of pollen-related symptoms.3
Marker allergens and panallergens
- IgE mediated cross-reactions can occur between evolutionarily unrelated pollen and plant species. These reactions are mediated by panallergens, families of closely related proteins involved in vital functions which are widely distributed throughout nature.2
- Currently, only three protein families have been identified as pollen panallergens: profilins, polcalcins and non-specific lipid transfer proteins (nsLTPs).2
- Sensitisation to profilins can be associated with pollen- food syndrome (PFS). Generally, individuals are primarily sensitised to pollen profilins and successively develop cross-reactivity to foods2 such as melon and tomato4.
- Polcalcins are specifically expressed in pollen tissue and are highly cross-reactive. Therefore, sensitised patients can often display multiple sensitisations to various pollen sources (e.g. tree, grass and weed pollen).2
- LTPs are expressed in latex, weed pollen, tree pollen and plant-derived foods.2 Sensitisation to these proteins is especially relevant due to its clinical implications in Mediterranean regions.5,6
- Alternatively, some allergens are considered species-specific markers or allergens in which primary (genuine) IgE sensitisation is specific to the allergen source. These are defined as marker allergens.7
Allergen components in birch tree pollen
- Bet v 1 is a major allergen for and is used as the marker allergen for genuine sensitisation to birch tree and other trees within the Betulaceae family.8
- Bet v 2, Bet v 3 and Bet v 4 are all minor allergens and panallergens.7,9
Cross-reactivity of birch pollen allergens
- Bet v 1 can cross-react with major allergens from other tree pollens belonging to the Betulaceae and Fagaceae families within the order of Fagales: Aln g 1 (alder), Car b 1 (hornbeam), Cor a 1 (hazelnut), Que a 1 (oak), Fag s 1 (common beech).2
- Homologous proteins to Bet v 1 can also have cross-reactivity with Bet v 1 and may induce birch pollen oral allergy syndrome. These include proteins from several plant foods: Mal d 1 (apple), Cor a 1 (hazelnut), Pru p 1 (peach), Dau c 1 (carrot), Gly m 4 (soy).10
- Sensitisation to profilins and polcalcin-like proteins can also lead to cross-reactions with homologous allergens found within pollens from botanically unrelated species. However:
- profilins are recognised by 10–20% of patients primarily sensitised to birch pollen11–13
- polcalcin-like proteins generally sensitise ~10% of pollen allergic individuals14.
Component-resolved diagnostics (CRD) in tree pollen allergy
- Presence of cross-reactive allergens such as panallergens in whole extract allergen sensitisation tests (e.g. skin prick testing and IgE) can lead to misidentification of the genuine source causing the patient’s symptoms.8
- Such results are not false positives but are usually clinically irrelevant due to the lack of accompanying symptoms.7
- Overlapping of tree, weed and grass pollination periods can also cause difficulties in identifying the primary sensitisation source.8,15
Alternatively, CRD can:
- distinguish cross-reactive and species-specific sensitisation, g. the use of panallergens and marker allergens in tree pollen allergies8,15–17
- support decisions on immunotherapy – for example, low IgE to marker allergens can rule out allergen immunotherapy specific to that allergen source8,15–17
- provide a targeted approach to determining sensitisation to both major and minor allergens7.
Using CRD in the diagnosis of birch and ash pollen allergies
- Components for testing should generally be selected on the basis of the patient’s clinical history, symptoms and any previous results of allergy sensitisation tests.7,8,18
- For individuals with a suspected tree pollen allergy that display multisensitisation in initial allergen sensitisation tests (i.e. skin prick tests or specific IgE blood tests to whole extracts), marker allergens for the suspected pollen allergy and panallergens should be selected for CRD:7,8,19
How can component-resolved testing help simplify the diagnosis of tree pollen allergy?
- Plant panallergens belong to the profilin, polcalcin and nsLTP protein families.
- Sensitisation to these protein families is not always clinically relevant but can confound whole extract sensitisation test results in patients with multiple pollen sensitisations
- Marker allergens are species-specific or allergens in which primary (genuine) IgE sensitisation is specific to the allergen source.
- In birch tree pollen:
- Bet v 1 is a marker allergen (also for beech tree pollens and other Fagales trees)
- Bet v 2, 3 and 4 are panallergens
- Selection of marker allergens and panallergens for CRD aid in the identification of the primary (genuine) allergen source causing the patient’s symptoms.