Variability of Ole e 9 Allergen in Olive Pollen Extracts: Relevance of Minor Allergens in Immunotherapy Treatments

Abstract

Background: Clustered severe adverse reactions to immunotherapy with olive pollen extracts have been occasionally reported in areas where olive trees are extensively grown. Allergic patients from these areas, in addition to the major olive pollen allergen Ole e 1, frequently recognize a recently described allergen, Ole e 9. Objective: We aimed to develop an immunoassay to measure Ole e 9 concentration and to study the variability of this allergen in olive pollen extracts. Methods: Monoclonal antibodies (mAb) to Ole e 9 were produced from mice immunized with the pure allergen. One of these mAbs was used to develop a sandwich ELISA with an anti-olive pollen extract rabbit serum as the tracer. Olive pollen batches from several suppliers were analyzed using this method. These batches were also analyzed for Ole e 1 content and biological activity. Results: A 10-fold variation between the extreme values was found for the biological activity of the batches analyzed. Ole e 1 concentration showed a 25-fold variation. Variability of Ole e 9 concentration was extremely high, up to 161 times. The ratio Ole e 1/Ole e 9 varied in a range from 0.6 to 390.4. Conclusion: The availability of a mAb-based ELISA for Ole e 9 made it possible for us to detect an important source of variability in olive pollen batches. This variability may be the cause of outbreaks of adverse reactions in the course of immunotherapy treatments, which have sometimes been observed among olive-allergic patients living in areas with very high levels of airborne olive pollen.

A Molecular Diagnostic Algorithm to Guide Pollen Immunotherapy in Southern Europe: Towards Component-Resolved Management of Allergic Diseases

“…Of course, for the moment, these remain mainly theoretical considerations; significant limitations include incomplete and sometimes conflicting published data, inadequate information about the allergen content of commercial SIT extracts as well as reported qualitative and quantitative variability between different SIT products and manufacturers [12,31,86,87,88]. In addition, taking into account the limited number of allergen components currently available for clinical use and the fact that exact matching of natural SIT extracts to individual sensitization profiles may probably be a Utopian goal, one could reasonably argue against the practical value of such an attempt.…”

The Principle of Homologous Groups in Regulatory Affairs of Allergen Products – A Proposal

“…The minor olive allergen Ole e 3, a calcium-binding protein/polcalcin, is a pan-allergenic structure and homologues have been described in ash and lilac [24,25,26]. The β-1,3-glucanase Ole e 9 is a major allergen, and although respective allergens have not been identified in the remaining Oleaceae species, cross-reactive structures have been detected in ash, lilac and privet [27,28,29]. According to one reference [30], a 11-kDa allergen, named Ole e 10 by the authors, has been identified as glycosyl transferase.…”

Solution structure of the C‐terminal domain of Ole e 9, a major allergen of olive pollen

“…To date, 10 allergens from olive pollen, Ole e 1-Ole e 10, have been characterized (Rodríguez et al 2002;Barral et al 2004), but only the three-dimensional (3D) structure of Ole e 6 has been determined (Treviño et al 2004). Among them, Ole e 9 is important because it has been described as a potential cause of adverse reactions in specific immunotherapy (SIT) (Duffort et al 2006). Ole e 9 is composed of two structurally and immunologically independent domains: N-and C-terminal domains (NtD and CtD, 36 kDa and 10 kDa, respectively), which can be separately produced by recombinant DNA technology (Palomares et al 2003(Palomares et al , 2005.…”