Oleaceae molecular allergens

Maria Teresa Villalba Diaz

Présentation disponible


PDF - 4.4 Mo
Oleaceae molecular allergens

Olive pollen is one of the most important causes of pollinosis in the Mediterranean basin and reaches the first position in the ranking of allergic pollens in several Spanish and Italian provinces. Factors such as the overlap in the pollination of several species, different pollination intervals between geographical areas and strong pollen gradient from Nord to South of Spain make difficult to diagnose and select the therapeutic strategy to follow. Pollen sensitization is usually restricted to anemophilous plants, in the case of Oleaceae, mainly ash and olive. Privet, lilac, and forsythia which are entomophilous pollens, contain allergen homologues but allergy to their pollens are very scarce. Anemophilous pollens are small, dehydrated with good aerodynamic properties that allow its dissemination over hundreds of kilometers. Grains are not usually transported intact and so subpollinic particles and nanovesicles named pollensomes carrying allergens seemed to be a widespread mechanism of allergens in many clinically relevant species during in vitro germination. When IgE binding to the protein extract of olive pollen is analyzed a complex and varied allergogram is observed. There are many different IgE-reactive bands in Western blots, immunostained with individual sera. There are several structural and functional parameters that can make a protein an allergen, although none of them are absolutely determinant. Location in pollen, solubility, size and concentration, glycosylation and polymorphism, changes in 3D structure because of their thermal and enzymatic stability and finally their biologic function. At present, fifteen allergenic proteins (Ole e 1 to Ole e 15) with varied clinical incidence have been identified in olive tree (fourteen in pollen and one in olive fruit) with molecular masses between 35 to 65 kDa, around 20 kDa and 6 proteins of smaller size. All of them have been produced as recombinant forms in bacteria, yeast, insect cells, Arabidopsis. Allergens already identified from olive tree can be classified in fifteen families of enzymes involved in the carbohydrate metabolism for remodelling of the pollen wall (polygalacturonases, glucanases, pectin methylesterases) and redox metabolism (superoxide dismutase or isoflavone reductase), in changes in the cytoskeleton (profilin), and ligand-binding and regulatory proteins such as Ole e 1, as calcium sensors (polcalcin) and in cellular signalling (LTPs). These allergens have been purified and their molecular features have been analysed. Most of them are acidic proteins with the exception of Ole e 7, our LTP, with a pI of 9. Regarding molecular masses, Ole e 6 is the smallest allergen with a polypeptide chain of 50 amino acids. Some are highly polymorphic as Ole e 11 and several are glycoproteins. Sensitivity to Ole e 1 indicates genuine sensitization to Oleaceae. Ole e 1 is a glycosylated allergen with a heterogeneous glycan able to bind IgE without a clinic repercussion. It is the most abundant protein in pollen and is a specifically expressed in pollen. Allergenic counterparts of Ole e 1 have been reported in other pollens, and they constitute a widespread Ole e 1-like family. Their members exhibit a broad degree of amino acid sequence identity, being high (> 80%) among Oleaceae members (Fra e 1 from ash, Lig v 1 from privet, and Syr v 1 from lilac) and low (25-45%) within not botanically related species such as ryegrass, Lambs´quarter, English plantain, Salsola, or birch. The high similarity among Oleaceae members of the Ole e 1-like family explains the high cross-reactivity in this family and the absence in non-related members. Ole e 7, together with Par j 1 other lipid transfer protein, does not show significant sequence similarity with allergenic LTPs from foods such as Pru p 3 or Sin a 3, and therefore both allergens should not be included in the LTP syndrome as Art v 3 and Pla a 3 are. Ole e 2 and Ole e 3 are panallergens and should be used indistinctly in diagnosis. Ole e 9 is composed of two well defined domains : An N-terminal domain with catalytic activity as -1,3-glucanase and a C-terminal domain with carbohydrate-binding capacity. Since 1,3--glucanases specially the short ones, are widely spread in plants, sera from olive pollen allergic patients rendered cross-reactivity with ash and birch pollen, tomato, potato, bell-pepper, banana and latex. Ole e 10 is an independent protein described as new allergenic family of carbohydrate-binding modules (CBM-43). It exhibits with a significant amino acid sequence similarity to the C-terminal domain of Ole e 9 and to glucanases from other species, which explains the existence of inter- and intra-species cross-reactivity. Proteomic tools allowed identified Ole e 12, an isoflavone reductase, and Ole e 15, a cyclophilin, whose pI and molecular mass overlap with those of other relevant allergens of olive pollen. Several problems associated to diagnosis and immunotherapy of olive pollen –allergic patients are the low concentration in the allergenic extracts that make allergens misrepresented and could not be enough to diagnose a patient and the high number of olive varieties growing in different cultivars even in the same cultivar renders a high variability in the amounts of several pollen allergens, such Ole e 9, from batch to batch that can produce adverse reactions during treatments. As biological activity is linked to the major allergen concentration, routine standardization might lead to a strong variability in minor allergen concentration. The strong olive pollen gradient generates different prevalence of certain allergens that is detected in specific geographical areas. Clinical incidence of Ole e 7 and Ole e 9 in Madrid are less 10%. They reach 50 and 60%, respectively, in allergic populations exposed to high pollen levels. Besides Ole e 7 and Ole e 9 are severity markers and Ole e 7 present a risk to adverse reactions during immunotherapy. Ole e 10 is a marker to develop asthma. Finally, Olive thaumatin, is the main allergen from olive fruit. Olive fruit allergy can only be an occupational problem in workers from olive mills as the protein is destroyed during olive fruit processing to make it edible.