How allergen cross-reactivity can help you formulate allergen specific immunotherapy for your cases

There are a number of points to consider when formulating allergen specific immunotherapy (ASIT) for your cases, one of which is the occurrence of cross-reactivity between allergens. Knowledge of allergenic cross-reaction can be used as a guide, alongside the animal’s clinical history, to assist with allergen extract choices.

Understanding plant taxonomy and allergenic cross-reactivity

Plant systematics infers that strong cross-reactions are seen between allergens with closely related compositions and protein structures (same genus), and that moderate cross-reactions are seen between allergens with similar compositions but with different structures (same family or sub-family). It is generally accepted that closely related plants will have a higher number of shared antigens and epitopes than distantly related ones. There are exceptions to this rule where cross-reactivity is seen across different kingdoms, although this tends to relate to minor allergens (Weber, 2008) and therefore is less relevant for ASIT formulation.

Cross-reactions to consider when selecting allergens for immunotherapy


Some of the strongest cross-reactions are seen in the grass family, particularly within the sub-family most relevant to the UK; Pooideae (northern pasture grasses). Examples of grasses which fall into this group are timothy, sweet vernal, orchard grass, fescue and blue grass (meadow grass). Weber (2008) suggests that in some cases timothy alone might be adequate to represent this sub-family, but that the use of additional members may be needed for optimal concentrations. In particular, in locations where sweet vernal is prevalent it is advised to prioritise this species for the best chance of success.


Cross-reactivity among tree pollens is not as prevalent as it is in grasses, but it does occur. Trees such as juniper, cedar and cypress are all members of the Cupressaceae family and strongly cross-react (Barletta et al, 1996). Similarly, the Betulaceae family (birch, alder and hazel) and the Fagaceae family (oak, beech and chestnut) show strong cross-reactivity between both families (Lowenstein, 1980). Where cross-reactions like these are seen within (or between) families, the use of one locally prevalent allergen is often adequate. However, in some cases allergens should be included separately for example Weber (2008) advises that pines and spruces from the Pinaceae family should be considered individually.


Cross-reactivity of weed species tends to be limited to within a genus; for example sheep’s sorrel and dock, or mugwort and wormwood.  As mentioned previously, after a full evaluation of the case, you may choose to treat with just one of the two members. Other weeds such as nettle, English plantain and pellitory should be included separately as they have been shown to have unique antigens (Weber, 2008).

Dust Mites

The most prevalent house dust mites are D. pteronyssinus and D. farinae which are members of the same genus. Although they do have allergens with extensive cross-reacting epitopes, they also have unique epitopes so they should generally be considered individually where possible (Cox et al, 2011).


Top tips!

  • Generally, closely related species will have a higher number of shared antigens (although remember there are always exceptions)
  • The most prevalent cross-reactions are seen amongst the grasses, therefore in many cases you will not need to include all species in the ASIT
  • There are varying levels of cross-reactivity seen amongst trees, weeds and mites
  • You should take into account regional significance of plants and prioritise those you know the animal will be exposed to more frequently
  • If cost is an issue for your client, or if only one injection of therapy is preferable due to behavioural issues, knowledge of cross-reactivity will be helpful
  • Pollen mixes which contain a number of different allergens may also be available and may be useful when trying to decrease the total number of allergens in a therapy


If you would be interested in learning more about how to get the most out of ASIT the following webinar presented by Dr Tim Nuttall may be of interest:

For more advice on allergen selection Avacta Animal Health’s customer services team are available by phone 0800 3047 047 or email and always happy to help!


Did you know? Cross-reactivity also occurs between food proteins so is something to consider when selecting novel proteins for cases which require a diet elimination trial.


Written by Emma Kilmurray – Customer Services Advisor


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Barletta B, Afferni C, Tinghino R, Mari A, Di Felice G, Pini C (1996) Cross-reactivity between Cupressus arizonica and Cupressus sempervirens pollen extracts. JACI. 797-804.
Cox L, Nelson H, Lockey R (2011) Allergen immunotherapy: A practice parameter third update. JACI. 37-38.
Lowenstein H (1980) Cross reactions among pollen antigens. Allergy. 198-200.
Weber, RW (2008) Guidelines for using pollen cross-reactivity in formulating allergen immunotherapy. JACI.  219-221.