Phl p 1
Summary
Phl p 1 allergen derived from timothy grass (Phelum pratanse) pollen is one of the distinguished group 1 grass pollen allergens. Group 1-grass pollen allergens are glycosylated proteins with a molecular weight of ~30 kDa that appear as cross-reactive antigens in majority of the grasses and corn species. Group 1 grass pollen allergen belongs to the subclass beta-expansin (EXP-B) of the expansin protein superfamily, which is involved in cell wall loosening and extension in the plants.
Phl p 1, the major allergen of timothy grass is identified by more than 90% of grass pollen-allergic patients. This allergen is highly cross-reactive among all the grass species of temperate and tropical regions and shows 90% sequence identity with allergens of other members of the Pooideae subfamily. A major IgE-reactive segment of Phl p 1 allergen reveals a substantial sequence identity of about 40% with the family of immunoglobulin domain-like group 2/3 grass pollen allergens.
Phl p 1 initiates sensitization in majority of the pediatric allergic rhinitis (AR) patients, followed by sensitization of these patients to other timothy grass pollen allergens (such as Phl p 5, Phl p 4, Phl p 2, and Phl p 6, and Phl p12).
Recombinant pollen allergens aid in lowering the number of allergens required for appropriate diagnosis of grass pollen allergy. Only a limited number of recombinant timothy grass pollen allergens results in the determination of a high percentage of patients with grass pollen-specific IgE. This indicates the benefits of recombinant allergens not only for in vitro diagnosis but also to evaluate the specific percentage of IgE produced by individuals against some allergens.
Epidemiology
Worldwide distribution
Phl p 1 allergen is found in grass species of both temperate and tropical regions of the world. A study using sera from European, Asian, and American subjects assessed the percentage of IgE directed to pollen extracts from nine different monocot species including rPhl p 1, rPhl p 2, rPhlp 5 of timothy grass and rBet v 2 of birch pollen. The study results showed that IgE antibodies to these four recombinant pollen allergens accounted for a mean of 59%. A study from China detected that out of all timothy grass serum(s) IgE positive patients only 17.1% were positive to the antigen Phl p 1 and 100% were positive to Phl p 4. A longitudinal birth cohort study in Germany investigated the evolution of IgE sensitization to P. pratense allergenic molecules in children suffering from seasonal AR due to grass pollens. The study detected Phl p1 initiated sensitization in more than 75% of these patients followed by sensitization to other allergens. Moreover, Phl p 1, Phl p 5, and Phl p 4 were the most frequently identified molecules in the preclinical sensitization phase.
Röschmann et al. (2011) studied the response of airway epithelium to Phl p 1, with an aim to obtain an insight into the immunostimulatory capacity of Phl p 1. They observed that Phl p 1 triggers the release of a wide range of mediators (IL-6, IL-8, TGF-β), which in turn attract and influence the immunocompetent cells’ activities. Hence, Phl p 1 is a powerful inducer of the immune system and linked with allergic respiratory diseases, especially AR.
Clinical Relevance
Specific molecules
Recombinant Phl p 1 (rPhl p 1) is a non-glycosylated protein produced in an Escherichia coli (E. coli) strain that carry a cloned cDNA encoding P. pratense allergen Phl p 1. rPhl p 1 closely resembles the natural Phl p 1 and binds to IgE in majority of the patients with grass pollen allergy, indicating that rPhl p 1 shares many of the IgE epitopes with natural group 1 grass pollen allergens. rPhl p 1 is considered to be one of the most important “species specific allergens” of timothy grass followed by rPhl p 5. Scaparrotta and colleagues (2013) detected rPhl p1 to be the predominant sensitizing allergen at all ages of pediatric population and at all levels of timothy grass pollen specific IgE molecules. Another study assessing specific IgE levels to the clinically relevant timothy grass pollen allergens found the level of Phl p 1 to be significantly higher (p=0.02) in children with moderate AR than in children with mild AR indicating the ability of Phl p 1 to induce allergic symptoms in AR patients.
Douladaris et al. (2019) constructed a recombinant hybrid molecule with four major timothy grass pollen allergens, Phl p 1, Phl p 2, Phl p 3, and Phl p 6 for in vitro serological testing and in vivo diagnosis of grass pollen allergy in adult patients. The success of this hybrid molecule suggested that all grass pollen allergen patients showed IgE reactivity and also positive skin reaction to this molecule.
Cross-reactive molecules
IgE antibodies from grass pollen allergic patients and also group 1 specific antibodies are found to cross-react with natural group 1 grass pollen allergens of different grass species. rPhl p 1 has been shown to inhibit IgE antibody binding to most of the group 1 isoallergens from 7 to 8 grass species indicating wide-spread cross reactivity between different grass species. Hence, a single recombinant group 1 allergen contains many of the IgE epitopes of group 1 isoallergenic variants from several different grass species. The major timothy grass pollen allergen Phl p 1 shows cross-reactivity with most grass, corn, and monocot-derived group 1 allergens.
Diagnostics
AIT Prescription
Allergic Immunotherapy (AIT)
The use of allergen immunotherapy (AIT) have increased owing to rise in the number of patients with respiratory allergic disease and have shown long-term benefits. The development of recombinant allergens (such as rPhl p1) helps to develop patient-tailored immunotherapy.
Exposure
The major grass pollen allergens, such as Phl p 1 are usually present within the pollen grain in a typical pattern and at the time of activation, allergen moves from the exine of the pollen grain to the surface in order to be released. Activation of the pollen grain leads to allergen release (normally under humid condition) at the mucosal surface of the nose and triggers allergic reactions.
Cross-Reactivity
Phl p 1 allergens are extremely cross-reactive allergens in majority of the grass species of temperate and tropical regions.
References
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