g212 Phl p 12

Summary

Phl p 12 is a minor allergen from timothy grass (Phleum pratense) pollen belonging to the profilin family of plant panallergens. It is a non-glycosylated protein that binds actin from the cytoskeleton pf plant cells. 

Epidemiology

Worldwide distribution

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).

Phl p 12 is a minor allergen of timothy grass pollen, binding IgE from approximately 15% of grass-allergic patients (1, 3). The prevalence of Phl p 12 sensitization in grass-allergic patients may be higher in regions with high levels of grass pollen counts (1, 3). Phl p 12 sensitization was found in 20% and 23% among Italian children aged 4 to 18 with asthma or allergic rhinitis (AR), included in two separate cross-sectional studies (4, 5), but in only 9.5% of children with grass pollen AR from the prospective German birth cohort MAS (6). In an unselected population of 23,077 consecutive Italian subjects with a suspicion of airborne or food allergy, the prevalence of IgE sensitization to Phl p 12 was 3.36% (7).

The Swedish birth cohort BAMSE provided data in pediatric general population. Sensitization to Phl p 12 was detected in none of 763 pediatric subjects at the age of 4 years, in 0.3% at age 8, and in 0.7% at age 16 (8).

Apparent monosensitization to Phl p 12 is infrequent, reported at 3% or less among grass allergic patients (4, 9). 

Environmental Characteristics

Source and tissue

Profilins are a family of highly conserved eukaryotic proteins, present in all plant and animal cells, that bind to actin filaments and participate to cytoskeleton regulation (1, 3, 10). As such, Phl p 12 is located in the cytoplasm of timothy grass pollen grains (10).

Clinical Relevance

Detailed information regarding timothy grass pollen is available in the whole allergen section. Timothy grass pollen induces AR, allergic rhinoconjunctivitis, and exacerbates asthma in sensitized individuals (2). There is a high degree of cross-reactivity between timothy grass and other grass pollens (3). In addition to cross-reactivity supported by grass marker allergens, such as Phl p 1, Phl p 5, Phl p 4, or Phl p 6, panallergens such as Phl p 12 (profilin) and Phl p 7 (polcalcin) contribute to extended cross-reactivity with unrelated products. Both Phl p 12 and Phl p 7 are responsible for cross-reactivity with pollens from trees or weeds, but only Phl p 12 is able to induce cross-reactivity with plant food (1, 3, 9, 10).  

Clinical relevance in respiratory allergy

Phl p 12 sensitization is a late event in the natural history of grass pollinosis, observed in patients who have a longer duration of grass allergy symptoms and a more complex sensitization profile (1, 6). The exact contribution of Phl p 12 to symptoms of grass pollinosis is not accurately determined, because of its panallergen status, i.e. it occurs in association with sensitization to major allergens from other pollen sources (trees, weeds). Thus, Phl p 12 sensitization is a marker of broad cross-reactivity with virtually any pollen or plant food(10) . 

Oral allergy syndrome and severe food reactions

Oral allergy syndrome (OAS) consists of symptoms such as perioral and oral itching and swelling immediately following food consumption. OAS development in a pollen allergic patient upon consumption of unrelated plant foods is suggestive of profilin involvement(1, 4, 10) .Phl p 12 sensitization is a biomarker of OAS (9). Frequent OAS due to pollen-food cross-reactivity via Phl p 12 has been reported for Cucurbitaceae (melon, watermelon, cucumber, zucchini), Rosaceae (peach, apple, pear, apricot, cherry, almond), banana, kiwi, soy, and others (1, 4, 10, 11).

Severe food reactions to Phl p 12 are infrequent, but must be considered in food-allergic patients from areas with high exposure to grass pollen(1, 4, 11) .

Disease severity and prediction

Sensitization to Phl p 12 is usually detected in grass allergic patients years after the onset of symptoms (1, 6). Sensitization to Phl p 12 is almost constantly associated with sensitization to major grass pollen allergens, and a distinct source of primary sensitization should be considered if sensitization to Phl p 1 and Phl p 5 is lacking(1, 4, 9, 10) .

Grass-allergic patients sensitized to Phl p 12 display an increased risk for pollen-food induced OAS (1, 4, 9, 10).

In the birth cohort BAMSE, Phl p 12 sensitization at age 8 in subjects without grass allergy symptoms was associated with the development of grass pollen AR by the age of 16 (8). However, due to the very rare occurrence of Phl p 12 sensitization at age 8, this result did not reach statistical significance. 

Cross-reactive molecules

Clinically significant cross-reactivity of Phl p 12 is observed with virtually all profilins from higher plants, due to sequence homology of 80% or higher(1, 10) .

Prevention and Therapy

Experimental trials

Phl p 12 induces basophil activation ex vivo(12) but is considered a weakly allergenic molecule (1).

Molecular Aspects

Biochemistry

Phl p 12 is an acidic monomeric protein with a molecular weight of 14 kDa, heat-labile and readily degraded by pepsin (3, 10, 13). 

Isoforms, epitopes, antibodies

As of August 15th, 2021, three isoallergens of Phl p 12, i.e. Phl p 12.0101, Phl p 12.0201, and Phl p 12.0301, have been officially published by the World Health Organization (WHO) and International Union of Immunological Societies (IUIS) Allergen Nomenclature (13).

Cross-reactivity due to structural similarity

Phl p 12 displays extensive sequence identity and conformational similarity to other profilins (1, 3, 10)

Molecular spreading

Upon exposure of predisposed individuals to grass pollen, sensitization to Phl p 12 is a late, although infrequent event (1, 6, 8)

Diagnostic Relevance

Disease Severity

Sensitization to Phl p 12 is a risk marker of OAS (1, 4, 10)(2,4,10). A history of plant food-induced reactions must be asked for in grass allergic patients sensitized to Phl p 12 (1)

Cross-Reactivity

Phl p 12 cross-reacts with similar proteins from other pollens and plant foods, making it a suitable biomarker of sensitization to the panallergen family of profilins. 

AIT Prescription

Phl p 12 is not a candidate molecule for AIT (5, 14)(5,14). Phl p 12 sensitization may affect the efficacy of AIT if it is not associated with sensitization to the corresponding major allergens (1, 10)

Exposure

The main route of exposure is through inhalation of timothy grass pollen(1, 3)

Compiled By

Author: Joana Vitte

Reviewer: Dr. Christian Fischer

Last reviewed: November  2021