Molecular biomarkers for grass pollen immunotherapy

Abstract

Grass pollen allergy represents a significant cause of allergic morbidity worldwide. Component-resolved diagnosis biomarkers are increasingly used in allergy practice in order to evaluate the sensitization to grass pollen allergens, allowing the clinician to confirm genuine sensitization to the corresponding allergen plant sources and supporting an accurate prescription of allergy immunotherapy (AIT), an important approach in many regions of the world with great plant biodiversity and/or where pollen seasons may overlap. The search for candidate predictive biomarkers for grass pollen immunotherapy (tolerogenic dendritic cells and regulatory T cells biomarkers, serum blocking antibodies biomarkers, especially functional ones, immune activation and immune tolerance soluble biomarkers and apoptosis biomarkers) opens new opportunities for the early detection of clinical responders for AIT, for the follow-up of these patients and for the development of new allergy vaccines.

Polcalcins as pollen panallergens in allergic rhinitis

“…This class is responsible for allergic reactions to a multitude of evolutionary unrelated pollen and food allergen sources. Being present exclusively in pollen grains of plants, polcalcins are not involved in pollinosis-associated plant food allergies, but may be discussed in allergic reactions to ingestion of edible products containing pollen grains of specific plants 9,11,24 . In a case of urticaria to Stigma maydis infusion, high level of specific IgE against polcalcin rPhl p 7, calcium-binding protein likely to cross-react with Zea m 7 from maize pollen, was reported 24 .…”

“…The hierarchy of IgE cross-reactivity was established for important polcalcins (rPhl p7 > rAln g 4 > rJun o 4 > rBet v 3), and identified rPhl p 7 as the EF-hand allergen component containing most IgE epitopes 31 . From the pollen polcalcins available for routine use, recombinant non-glycosylated calcium-binding protein of 2-EF-hand type, the grass allergen component rPhl p 7, is the most cross-reactive polcalcin and it may serve as efficient biomarker of IgE-mediated hypersensitivity to this entire group of homologous proteins 9,23 . Recently, Sorghum bicolor polcalcin (Sor b 7) was found to be closely related with polcalcins from Cynodon dactylon, Phleum pratense and Oryza sativa grass species 32 .…”

“…Some opinions consider that the added value of component-resolved diagnosis mainly lies in the correct identification of allergic rhinitis patients who are not sensitized to major pollen allergens and in whom prescription of allergen immunotherapy is anticipated, as patients sensitized to minor allergens alone are unlikely to receive sufficient amounts of responsible allergen to achieve a successful outcome 10 . The application of in vitro component-resolved approach to the selection of patients more likely to better respond to allergen immunotherapy has been suggested, with the hypothesis that multisensitized patients with broad patterns of IgE reactivity to multiple minor allergens, or cross-reactive panallergens such as profilins or polcalcins, may show poor responses to allergen immunotherapy 9,13 . In some authors experience, at least for grass pollen sublingual immunotherapy, this type of therapy was found to be efficacious irrespective of the patients' baseline IgE sensitization profiles 14,15 .…”

“…Candidates biomarkers for molecular allergy diagnostics to identify specific allergen sensitivities to major pollen allergen markers are Bet v 1 (Fagales trees from the Betulaceae and Fagaceae families, such as birch, hazel, alder, beech and oak), Ole e 1 (Oleaceae family plants, such as olive and ash), Jun a 1 (cedar, cypress), Phl p 1/5 (Pooideae subfamily grasses), Amb a 1 (ragweed), Art v 1 (mugwort) and Par j 2 (pellitory) 9,12,13 . Some opinions consider that the added value of component-resolved diagnosis mainly lies in the correct identification of allergic rhinitis patients who are not sensitized to major pollen allergens and in whom prescription of allergen immunotherapy is anticipated, as patients sensitized to minor allergens alone are unlikely to receive sufficient amounts of responsible allergen to achieve a successful outcome 10 .…”

“…Component-resolved specific diagnosis is also important due to the high heterogeneity of geographically-related sensitization profiles. Moreover, molecular-based diagnosis improves the understanding of clinically relevant IgE sensitization to cross-reactive allergen components from aeroallergen sources and foods [8][9][10][11][12] .…”