Molecular allergy diagnosis using pollen marker allergens and pollen panallergens: Five patterns seen in multiple test reactions to pollen extracts

Abstract

Polysensitizations to tree, grass, and weed pollen are found in ~ 20% of pollen-allergic individuals. They are often based on broad IgE cross-reactivities to pollen panallergens belonging to highly conserved protein families: 1. profilins, 2. polcalcins (calcium-binding proteins in pollen), 3. cyclophilins. They represent highly conserved cross-reactive minor allergens present in all pollen species, but also in plant foods and other organisms. Despite being rarely clinically relevant they can hamper allergy diagnostic tests with extracts. In this situation, molecular allergy diagnosis is able to distinguish broad cross-reactivity due to allergen-specific IgE to pollen panallergens (i.e. profilins Bet v 2 or Phl p 12; polcalcins Bet v 4 or Phl p 7; and, in the future, cyclophilins Bet v 7 or Ole e 15) from primary IgE sensitizations to so-called marker allergens represented by important pollen major allergens: Bet v 1 for the birch and beech family (Fagales), Ole e 1 for olive and ash (Oleaceae), Phl p 1 for temperate climate grasses (Poaceae), Art v 1 for mugwort (Artemisia), Amb a 1 for Ambrosia species (Ambrosia). Five typical cases (A - E) with positive skin prick test results to tree, grass, and weed pollen extracts demonstrate typical patterns of IgE sensitization with a variable impact of pollen panallergens: A - profilins, B - polcalcins, C - profilins and polcalcins, D - presumably cyclophilins, E - primary polysensitization to tree, grass, and weed pollen without interference from profilins or polcalcins. Differences between pollen extract-based skin prick test diagnosis and molecular allergen-specific IgE testing are explained using the presented concept. This approach allows to reduce the number of allergen extracts - presuming they are also clinically relevant - for allergen immunotherapy (i.e., only tree and/or grass pollen extracts), particularly in pollen-polysensitized patients.

Keywords: IgE; allergen-specific IgE test; cross reactivity; cyclophilin; major allergen; pan-allergen; polcalcin; pollen; primary sensitisation; profilin; skin prick test (SPT).

Figure 1.. Updated propeller model for allergy diagnosis in case sensitization to pollen panallergens is suspected. Representative major allergens (“marker allergens” see propeller blades) for specific IgE diagnostics and highly cross-reactive panallergens (center of propeller) as a potential cause of multiple cross-reactions (positive tree, grass, and weed pollen) when using (pollen) extracts.

Figure 2.. Diagnostic algorithm for polysensitized patients with pollen allergy. Sensitizations against one or two groups of pollen (top left box) do usually not involve pollen panallergens. Diagnostic workup (e.g., skin prick test, specific IgE test) with pollen extracts is then sufficient to determine and distinguish important sensitizations (bottom left box). Only sensitizations to all three pollen groups (circle) can be based on highly cross-reactive pollen panallergens. Specific IgE tests using marker allergens (top right box) and one representative of each of the potentially involved pollen panallergens (bottom right box) allow reliable differentiation: 1. Primary sensitization against important allergen sources, yes or no? 2. Detectable cross-reactions caused by pollen panallergens, which family and which origin (pollen species)? Sensitizations against pollen panallergens (basically pollen minor allergens) are mostly caused by pollen with high seasonal exposure and the resulting broad and predominant sensitizations (e.g., against grass pollen) as reflected by the high specific IgE against the associated marker allergen (e.g., Phl p 1). *So far, no pollen cyclophilin is available for sIgE diagnostic workup so that not all cases of pollen polysensitization can be determined (see patient D). For allergen immunotherapy, if indicated, only pollen extracts with proven primary sensitization (positive marker allergen) and clinical relevance would be considered in polysensitized patients.