Phl p 1, Phl p 5b, Timothy
Summary
Phl p 5 is a group 5 pollen allergen of Timothy grass (Phleum pratnese). Group 5 grass pollen allergens have been found in several members of the Pooidieae subfamily. Phlp 5 is considered as one of the major “species-specific allergens” from timothy grass pollen. Approximately 65-90% of grass pollen sensitized individuals in temperate climate areas are found to be positive for Phl p 5.
Group 5 allergen of timothy grass has a molecular weight of 28-32 kilodalton (kDa) and consists of two isoforms: Group 5a and Group 5b with wide variation in IgE epitopes, which can explain its high allergenicity. Phl p 5b is smaller in size than 5a and has a molecular weight of 32 kDa. Variants of Phl p 5b of timothy grass reveal a 25-30% amino acid sequence divergence.
Phl p 5b is a major allergenic molecule of timothy grass pollen due to its structural characteristics that aid in effector cell activation. It is a key target of IgE antibodies among 80-95% of grass pollen allergic patients. Adults are found to be more sensitized to Phl p 5b compared to the pediatric population. Recombinant Phl p 5b or r Phlp 5b shows quite a similarity with natural Phl p 5b and also possesses homology to other Group 5 allergens.
Phl p 5b is responsible for causing allergic rhinitis (AR) and bronchial asthma in grass pollen allergic patients. Phl p 5b has been shown to be cross-reactive with similar Group 5 allergens from several temperate grass species and also grain species
Epidemiology
Worldwide distribution
Timothy grass has a widespread distribution in the temperate climate; however, it is the most common sensitizing pollen in Europe. Among the European population, the sensitization to the timothy grass pollen has been found to be as follows in some of the countries including Germany about 28.5%, United Kingdom (UK) about 26.9%, Sweden 24.2%, Amsterdam 19.5%, Belgium 18.5% with a median prevalence of 16.9%. In Austrian students, a prevalence of 36% sensitization to timothy grass pollen was detected using allergen microarray analysis. Within the U.S., about 69% of the population is exposed to timothy grass. In Canada, the prevalence of sensitivity to timothy grass pollen usually varies between 20.2% and 23.3% with a median prevalence of 21.8% in patients with allergic rhino-conjunctivitis (ARC).
Phl p 5b sensitization has been detected in the western region of the United States and Canada. In a study with the Czech population, IgE sensitization to Phl p 5b was found to be less frequent in children than in adults with grass pollen allergy (59.8% vs. 79.1%; p= 0.023). One Italian study on the pediatric population detected a lower frequency of IgE sensitization to Phl p 5b compared to other timothy grass allergenic components: Phl p 1, Phl p 7, and Phl p 12. Similar to these findings, a study in Portugal detected that among 41 patients with respiratory allergic symptoms of unknown etiology, 13 adults and 7 children had sensitization to Phl p 5b. Moreover, in this study, the adults showed increased median values for Phl p 5b than children. A German study determined 81% sensitization for Phl p 5b among adult patients allergic to timothy grass and suffering from ARC. Likewise in one Spanish study with 138 adult patients suffering from grass pollen associated rhinitis and /or asthma, 62.8% of patients showed sensitization towards Phl p5b.
Phl p 5a and Phl p 5b possess considerably different patterns of IgE binding. In fact, in a study with 150 sera, 100 of the sera showed IgE reactivity to rPhlp 5a and all these sera showed binding of IgE to rPhlp 5b. Moreover, exclusive reactivity with rPhl p 5b was found among 19 out of 150 sera indicating that Phl p 5b has at least one key epitope for IgE antibodies, which is probably not present in Phl p 5a.
Clinical Relevance
Specific molecules
Phl p 5 (Group 5 allergen) of timothy grass has a molecular weight of 28-32 kilodalton (kDa) and consists of two isoforms: Group 5a and Group 5b. Phl p 5b is smaller in size than 5a.
Phlp 5 is considered as one of the major “species-specific allergens” from timothy grass pollen. Phl p 5b does not contain any consensus site for N-linked glycosylation but has 17 O-linked glycosylation sites. Variants of Phl p 5b of timothy grass reveal a 25-30% amino acid sequence divergence. The most common type of amino acid is alanine, whereas the amino acid cysteine, methionine, histidine, and tryptophan are rarely found in Phl p 5b.
Cross-reactive molecules
Phlp 5 is a heterogeneous group of proteins with isoforms a and b, having differences in primary sequences. Antibodies raised against Phl p 5 allergens failed to determine cross-reactive antigens outside of the subfamily Pooideae. In fact, Phl p 5b has been found to show cross-reactivity with some grasses.
Diagnostics
Disease Severity
Phl p 5b, the major Group 5 pollen allergen of timothy grass is responsible for causing AR and bronchial asthma in a large number of sensitized individuals globally.
Cross-Reactivity
The recombinant human IgE Fab had been found to cross-react strongly with Phl p 5 and other natural Group 5 allergen from different grass and corn species indicating that recombinant human IgE Fab is able to identify a cross-reactive epitope in Group 5 allergens from various grass and corn species. In fact, Phl p 5 shows cross-reactivity with other Group 5 allergens of the Pooideae subfamily of temperate grass and also corn species. Phl p 5 does not show cross-reactivity with the pollen of monocots.
Moreover, a recent study detected rabbit IgG antibodies raised against helminth Schistosoma mansoni soluble egg antigens (SmSEA) were cross-reactive with Phl p 5b and this was possibly due to the presence of similar glycans (CCDs) between helminths and plants.
References
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