Table 1 Rules implemented in the expert system Allergenius

Top level rules (examples)

1. IgE specific for a given allergen or component are signs of sensitization. Specific IgE and relevant clinical signs are indicative of an allergy.

2. Inhalant allergens are either genuine or cross-reactive.

3. Microarray allergens are classified as inhalants, food, contacts or venoms.

4. Allergens are classified as innocuous or potentially dangerous[8].

5. Components are classified as recombinant molecules (without glycidic chains, such as rPhl p 1) or highly purified extractive molecules (containing glycidic chains, such as nCyn d 1).

6. Relationships between microarray components and allergens:

 a) A positive component is generally associated with the positivity of the relevant allergen (e.g., der p 1 and D1 are positive).

 b) Negative components are generally associated with the negativity of the relevant allergen (e.g., Der p 1, Der p 2, Der p 10, Der f 1 and Der f 2 are negative, as well as D1).

 c) Negative components are sometimes associated with a positive allergen (e.g., Der p 1, Der p 2, Der p 10, Der f 1 and Der f 2 are negative and D1 is positive). However, the frequency of these cases is known[10], and the allergen score is generally very low.

 d) If one or more components are positive but the relevant extractive allergen is negative, the rare, and at least partially unexpected, discrepancy should be clearly reported.

Intermediate level rules (examples)

1. When > 40% of the components of a family of cross-reactive components are positive, a positivity towards the whole family must be considered[18].

2. Immunotherapy is more active if sensitization to one or a few genuine components is observed[5, 6].

3. More than three different families of allergens cannot be administered to the patients[30, 31].

4. According to the ratio between the genuine and cross-reactive components, different phenotypes are identified[29].

Low level rules (examples)

1. Very low levels of a component associated with a very high level of IgE to a cross reactive component are most likely associated with a cross reaction between the components. This positivity is trustable only if the clinical signs associated with sensitization to these low level IgE components are evident. (for example: Lep d 2 is weakly positive, and Der f 2 is strongly positive; a cross reaction, at least in the in vitro test, should be suspected based on the > 50% identities in the primary structures).

2. When a component is negative (e.g., Amb a 1) and the extractive allergen (Ambrosia a.) is positive, if all other cross-reactive components (such as profilins, PR-10, polcalcins) are also negative, even if belonging to other allergens, a real discrepancy is reported. The frequency of this discrepancy is calculated and shown in Allergenius, as well as the median score of ImmunoCAP for this category of allergens.