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

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.