g211 Phl p 11, Timothy

Summary

Phl p 11 is a minor allergen from timothy grass (Phleum pratense) pollen, belonging to the Ole e 1 family.  Its cross-reactivity is restricted to other group 11 grass pollen allergens, making it a marker of genuine sensitization to grass pollen. Phl p 11 sensitization is most often associated with sensitization to other grass pollen allergens. 

Epidemiology

Worldwide distribution

Grass pollens are the principal causes of respiratory allergic disease globally. Timothy grass has a widespread distribution in the temperate climate and is often the predominant grass pollen in such European and Asian regions, less so in Australia(1, 2). Timothy grass pollen induces allergic rhinitis, allergic rhinoconjunctivitis, and exacerbates asthma in sensitized individuals (1). There is a high degree of cross-reactivity between timothy grass and other grass pollens(3).

Phl p 11 was identified as a minor allergen of timothy grass pollen, binding IgE from 32% of grass-allergic patients (4). Later studies reported large variations in the prevalence of Phl p 11 sensitization in grass allergic patients, from 20% in a pediatric cohort to 60% in a mixed pediatric and adult cohort, both from Italy (5, 6). This might be due to the natural history of Phl p 11 sensitization. Upon exposure of predisposed individuals to grass pollen, sensitization to Phl p 11 is usually a late event in the molecular spreading process, once the individual has become sensitized to Phl p 1, then Phl p 4 or 5, and has developed symptoms of grass pollinosis (2, 7). In the German MAS birth cohort, taking the

age of grass pollinosis onset as a hallmark, the prevalence of Phl p 11 sensitization was less than 10% before the onset but higher than 30% after 4 years of symptoms(7).

The Swedish birth cohort BAMSE provided data in general population. Sensitization to Phl p 11 was absent at the age of 4 years and extremely infrequent at the age of 8 and 16 years (0.3% and 0.8% respectively) (8).

Apparent monosensitization to Phl p 11 in grass-allergic patients is rare (2,8), but has been observed in adults and in children (4, 7, 9). 

Environmental Characteristics

Source and tissue

In intact pollen grains, Phl p 11 is found in the cytoplasmic granule compartment (10). Pollen cytoplasmic granules are expelled from broken pollen grains and may become aerosolized, contributing to allergen spreading (10).

 Risk factors

Air pollution facilitates grass pollen rupture and hence Phl p 11 release(10).

Clinical Relevance

Disease severity and prediction

No association of Phl p 11 sensitization was found with more severe pollinosis symptoms, the presence of asthma, the duration of symptoms, the occurrence of oral allergy syndrome, or the prediction of later onset of grass pollinosis (8, 9). Data are lacking for the infrequent profile of Phl p 11 apparent monosensitization.

Cross-reactive molecules

Phl p 11 exhibits sequence identity of 50% or higher with Ole e 1, the major allergen of olive pollen, and other Ole e 1-related proteins from grasses, weeds, and trees. However, clinically significant cross-reactivity is observed only with grass homologues (2, 4, 11).

Molecular Aspects

Biochemistry

Phl p 11 is an acid peptide with a molecular weight of 20 kDa (2, 4, 12). Functionally, Phl p 11 is a trypsin inhibitor (2, 4)

Isoforms, epitopes, antibodies

As of August 15th, 2021, a single isoallergen of Phl p 11 i.e., Phl p 11.0101, has been officially published by the World Health Organization (WHO) and International Union of Immunological Societies (IUIS) Allergen Nomenclature (12).

Cross-reactivity due to structural similarity

Cross-reactivity of native Phl p 11 is related to both its protein moiety and its glycosylated lateral chains. The use or recombinant Phl p 11 prevents carbohydrate cross-reactivity, maintaining only the protein cross-reactivity limited to grass allergens group 11 (4). 

Diagnostic Relevance

Disease Severity

Sensitization to Phl p 11 has been associated with more complex sensitization profiles, hence with a more advanced stage in the natural history of sensitization to grass pollen allergens and a higher risk for symptomatic grass pollinosis (2, 7).

Cross-Reactivity

Phl p 11 cross-reacts with similar proteins from other temperate and subtropical grass species (2), making it a suitable biomarker of sensitization to grass allergens group 11. In grass allergic Brazilian subjects, who are exposed predominantly to Lolium multiflorum and Cynodon dactylon but not to Phleum pratense, the prevalence of sensitization to microarrayed Phl p 11 was 18% (13).

AIT Prescription

Phl p 1 and Phl p 5, but not Phl p 11, are usually employed when grass pollen allergen immunotherapy is considered, both as biomarkers for therapeutic response and in trials with molecular allergen immunotherapy (14). 

Exposure

The main route of exposure is through inhalation of timothy grass pollen.

Compiled By

Author: Joana Vitte

Reviewer: Dr. Christian Fischer

Last reviewed: November  2021