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Component

g210 Phl p 7

g210 Phl p 7 Scientific Information

Type:

Component

Name; WHO/IUIS:

Phl p 7

Biological function:

Unknown

Allergen code:

g210

Source Material:

Recombinant, CCD-free protein

Other Names :

Timothy grass pollen polcalcin

Summary

Phl p 7 is a minor allergen from timothy grass (Phleum pratense) pollen belonging to the polcalcin family of pollen panallergens. It is a non-glycosylated, calcium-binding EF-hand protein. 

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 (AR), allergic rhinoconjunctivitis (ARC), and exacerbates asthma in sensitized individuals (2)

Phl p 7 is a minor allergen of timothy grass pollen, binding IgE from 7-10% of grass-allergic patients, often less in pediatric patients (1, 3-5). 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 7 was 2.47% (6).

The Swedish birth cohort BAMSE provided data in pediatric general population. Sensitization to Phl p 7 was detected in none of 763 pediatric subjects at the age of 4 years, in 0.3% at age 8, and in 1.2% at age 16 (7).

Apparent monosensitization to Phl p 7 is infrequent (7) .

Clinical Relevance

Detailed information regarding timothy grass pollen is available in the whole allergen section. Timothy grass pollen induces allergic rhinitis (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). 

Disease severity and prediction

Sensitization to Phl p 7 is usually detected in grass allergic patients years after the onset of symptoms (1, 9). Sensitization to Phl p 7 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).

Grass-allergic patients sensitized to Phl p 7 display a more severe phenotype in terms of symptom severity, asthma prevalence and allergic comorbidities (1). Sensitization to Phl p 7 was also identified as a biomarker of asthma and more severe AR in a pediatric cohort of grass allergic patients (10).

In the birth cohort BAMSE, Phl p 7 sensitization at age 8 in subjects without grass allergy symptoms was associated with the development of grass pollen AR by the age of 16 (7). However, due to the very rare occurrence of Phl p 7 sensitization at age 8, this result did not reach statistical significance. 

Cross-reactive molecules

Clinically significant cross-reactivity of Phl p 7 is observed with other polcalcins from unrelated plant species (1, 8)

Prevention and Therapy

Experimental trials

Phl p 7 induces skin reactivity, in vitro histamine degranulation, and was identified as a potent allergen (1, 3, 4)

Molecular Aspects

Biochemistry

Phl p 7 is an acidic EF-hand, calcium-binding homodimeric protein with a molecular weight of 6 kDa.

Isoforms, epitopes, antibodies

As of August 15th, 2021, one isoallergen of Phl p 7 i.e., Phl p 7.0101, has been officially published by the World Health Organization (WHO) and International Union of Immunological Societies (IUIS) Allergen Nomenclature (11)

Cross-reactivity due to structural similarity

Phl p 7 displays extensive sequence identity and conformational similarity to other polcalcins (3, 4, 8)

Molecular spreading

Upon exposure of predisposed individuals to grass pollen, sensitization to Phl p 7 is a late event, although infrequent (1, 7-9).

Diagnostic Relevance

Disease Severity

Sensitization to Phl p 7 is a marker of more severe AR, higher risk of asthma and higher risk of other allergic comorbidities (1, 10). 

Cross-Reactivity

Phl p 7 cross-reacts with similar proteins from other pollens, making it a suitable biomarker of sensitization to the panallergen family of polcalcins

AIT Prescription

Phl p 7 is not a candidate molecule for AIT (5, 11)

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

References
  1. Davies JM MP, Schmid J. EAACI Molecular Allergology User’s Guide. Pediatr Allergy Immunol. 2016:1-250.
  2. Davies JM. Grass pollen allergens globally: the contribution of subtropical grasses to burden of allergic respiratory diseases. Clin Exp Allergy. 2014;44(6):790-801.
  3. Andersson K LJ. Characteristics and immunobiology of grass pollen allergens. Int Arch Allergy Immunol 2003:87-107.
  4. Niederberger V HB, Vrtala S, Laffer S, Twardosz A, Vangelista L, et al. Calcium-dependent immunoglobulin E recognition of the apo- and calcium-bound form of a cross-reactive two EF-hand timothy grass pollen allergen, Phl p 7. . FASEB J 1999(13):843-56.
  5. Tripodi S, Frediani T, Lucarelli S, Macri F, Pingitore G, Di Rienzo Businco A, et al. Molecular profiles of IgE to Phleum pratense in children with grass pollen allergy: implications for specific immunotherapy. The Journal of allergy and clinical immunology. 2012;129(3):834-9 e8.
  6. Scala E, Alessandri C, Bernardi ML, Ferrara R, Palazzo P, Pomponi D, et al. Cross-sectional survey on immunoglobulin E reactivity in 23,077 subjects using an allergenic molecule-based microarray detection system. Clin Exp Allergy. 2010;40(6):911-21.
  7. Westman M, Aberg K, Apostolovic D, Lupinek C, Gattinger P, Mittermann I, et al. Sensitization to grass pollen allergen molecules in a birth cohort-natural Phl p 4 as an early indicator of grass pollen allergy. The Journal of allergy and clinical immunology. 2020;145(4):1174-81 e6.
  8. Grote M, Westritschnig K, Valenta R. Immunogold electron microscopic localization of the 2 EF-hand calcium-binding pollen allergen Phl p 7 and its homologues in pollens of grasses, weeds and trees. Int Arch Allergy Immunol. 2008;146(2):113-21.
  9. Hatzler L, Panetta V, Lau S, Wagner P, Bergmann RL, Illi S, et al. Molecular spreading and predictive value of preclinical IgE response to Phleum pratense in children with hay fever. The Journal of allergy and clinical immunology. 2012;130(4):894-901 e5.
  10. Cipriani F, Mastrorilli C, Tripodi S, Ricci G, Perna S, Panetta V, et al. Diagnostic relevance of IgE sensitization profiles to eight recombinant Phleum pratense molecules. Allergy. 2018;73(3):673-82.
  11. Focke-Tejkl M WM, Niespodziana K et al. . Development and characterization of a recombinant, hypoallergenic, peptide-based vaccine for grass pollen allergy  J Allergy Clin Immunol 2015:e1-11.