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Component

w231 Art v 1

w231 Art v 1 Scientific Information

Type:

Component

Name; WHO/IUIS:

Art v 1

Biological function:

Defensin-like

Allergen code:

w231

Molecular Weight:

24-27 kDa

Route of Exposure:

Inhalation

Source Material:

Mugwort pollen

Other Names :

Defensin-like protein linked to polyproline-rich region

Whole Allergen: Mugwort
Related Allergens: w233 Art v 3

Summary

Art v 1 is one of the major allergens of mugwort (Artemisia vulgaris) with a reported prevalence among mugwort-allergic patients to be up to 95% depending on the geographical location. It is a defensin-like glycoprotein linked to polyproline-rich region with molecular weight varying between 24 and 28 kDa. Mugwort-allergic patients sensitized to Art v 1 can trigger allergic respiratory symptoms like allergic rhino-conjunctivitis and asthma. Such patients can also exhibit pollen-food-allergy symptoms like oral allergy syndrome, urticaria, angioedema and anaphylaxis. However, no significant difference has been found in their sensitization among food-allergic or food-tolerant patients. Further, native Art v 1 is shown to have higher reactivity than the recombinant Art v 1. Mugwort and ragweed exhibit substantial cross-reactivity among pollen allergic patients, may be due to cross-reactivity among Art v 1 and Amb a 4. Besides, Art v 1 is also responsible for cross-reactivity of mugwort with sunflower and chamomile. Importantly, Art v 1 may act as a prominent diagnostic marker for sensitization to mugwort pollen.

Epidemiology

Worldwide distribution

Artemisia vulgaris (mugwort) is a perennial weed widely distributed across Europe, North America, and Asia (1, 2) Inhalation of the pollen grains of mugwort can trigger type I allergic reactions (3, 4).

In Europe, mugwort pollens are a major cause of allergy. The sensitization rates among suspected allergy patients are between 10 % (Southern Europe) and 15 % (Northern Europe) (5, 6). Depending on the geographical region, up to 95 % of mugwort-allergic patients are sensitized to the major allergen Art v 1 (7-9). In a study in Spain, sensitization to Art v 1 was found in 75% of 24 mugwort-sensitized patients based on skin prick test (SPT), specific IgE, and the nasal provocation test (10). Further, in 100 pediatric mugwort-allergic patients (1-19 years) from Germany, 79% were found to be sensitized to native Art v 1 (nArt v 1) (11). Among 35 summer or spring pollinosis patients (sera samples) in Strasbourg, France, 17.6% were sensitized to mugwort-pollen allergen, Art v 1 (12).

Art v 1 was also the most commonly detected (81%; ranging from 53%‐93%) mugwort allergen among 240 patients (3-66 years), allergic to Artemisia pollen in a study conducted in different provinces of China (Shanxi, Shandong, Yunnan Province) (13). 

Environmental Characteristics

Source and tissue

The International Union of Immunological Societies (IUIS) has listed Art v 1, a defensin-like protein, as a major allergen from Artemisia vulgaris, mugwort pollen. It is mainly a two-domain glycoprotein  (8, 14).

Cation exchange chromatography and size-exclusion were some methods used for purification of natural Art v 1 from the mugwort-pollen aqueous extract. The molecule can also be generated by recombinant expression systems. Art v 1 was expressed in Escherichia coli and was further characterized by mass spectrometry and circular dichroism (9).

Clinical Relevance

Cross-reactive Molecules

Mugwort and ragweed (Ambrosia artemisiifolia) exhibit substantial cross-reactivity among pollinosis patients (17, 18). A study conducted on sera of patients allergic to ragweed and mugwort from Canada (8 sera), Italy (81 sera) and Austria (74 sera) found about 42% Art v 1 sensitized patients to be reactive with Amb a 4. This shows considerable cross-reactivity among Art v 1 and Amb a 4 (17).

Sunflower co-allergy in patients sensitized to mugwort may be due to cross-reactivity between Art v 1 and its homologous proteins in sunflower, Hel a 1 and Hel a 2 (5, 19). Mugwort-chamomile cross-reactivity was also reported and the possible cross-reactive allergen identified was Art v 1 (19).

Disease severity

A study conducted in Austria using sera of approximately 600 mugwort pollen allergic patients found Art v 1 serum specific Immunoglobulin E (sIgE)-reactivity on immunoblots in >95% patients (9). In a study conducted in China, 81.1% of 148 mugwort-allergic patients showed a positive reaction to sIgE of Art v 1. All these patients showed respiratory symptoms like allergic rhino-conjunctivitis and asthma in addition to food allergy symptoms like oral allergy syndrome, urticaria, angioedema and anaphylaxis. The Art v 1-sIgE levels were significantly correlated with whole mugwort pollen sIgE (correlation coefficient, r=0.802, p<0.01). However, no significant difference was found between Art v 1-sIgE levels in mugwort-allergic patients who were either allergic or tolerant to food (7).

Art v 1 can induce strong T-cell responses in the peripheral blood mononuclear cells (PBMCs) of mugwort allergic patients (15). Further, a study on 51 white mugwort-allergic patients has suggested Art v 1 to be a potential target for peptide immunotherapy owing to its consistent T-cell response and association with HLA-DRB1*01 phenotype (16).

Molecular Aspects

Biochemistry

Art v 1 is a part of defensin-like glycoprotein linked to the polyproline-rich region (14, 16). It possesses 108 amino-acids and comprises of 2 modules: a 53 amino-acid long C-terminal domain, rich in hydroxyproline, in the form of an extended ‘tail-like’ structure and a 55 amino-acid long, defensin-like N-terminal domain, rich in cysteine, as a condensed globular head (9, 16). The C-terminal domain is the site for post-translational modifications like proline hydroxylation and O-glycosylation (20).

The molecular weight of Art v 1 ranges from 24 to 28 kDa (16). The varied molecular weight is because the C-terminal hydroxyprolines that show different degrees of O-glycosylation (15). These wide-ranging carbohydrate structures that makeup 30–40% mass is found to be prominent in IgE recognition (9, 21).

Isoforms, epitopes, antibodies

Seven Art v 1 isoforms have been identified. These isoforms differ in the 1-6 amino acid residues [(one in isoform 6, three in isoforms 2 and 5, four in isoform 4, five in isoform 3 and six in isoform 1) (20).

Unlike other pollen allergens, Art v 1 possesses a minimal specificity for epitopes (21). However, the relevant immunoreactive IgE epitopes are found on the N-terminal defensin domain (all B-cell epitopes and only one T-cell epitope) (20). The sole immunoreactive T-cell epitope is Art v 1 that is identified by over 80% of mugwort allergic patients sensitized to Art v 1 (22).

Cross-reactivity

The mono-β-arabinosylated hydroxyprolines of Art v 1 are said to have cross-reactive carbohydrate determinants. Both cross-reactivity and IgE recognition essentially involves xylose and fucose residues (23).

Mugwort and ragweed are highly cross-reactive due to the presence of common allergenic structures on their pollens (18). The Art v 1 homologue protein with a defensin-like domain found in ragweed was reported to be Amb a 4. However, the proline-rich region of Amb a 4 differs from Art v 1 which affects the IgE binding in respective allergic patients (17).

Pollens from Asteraceae weeds that are botanically related [such as Artemisia absinthium (wormwood) and Helianthus annuus (sunflower)] possess Art v 1 cross-reactive structures, especially polypeptide and carbohydrate structures (23). Further, Hel a 1 and Hel a 4 are reported to be the homologous protein to Art v 1 in sunflower (5, 19).

Diagnostic Relevance

Disease Severity

Art v 1 acts as a prominent diagnostic marker for sensitization to mugwort pollen (13).

A study was conducted in Germany to differentiate the reactivity of nArt v 1 and recombinant Art v 1 (rArt v 1) on 32 mugwort-allergic and 10 control patients. The results revealed a significant correlation among both the forms in terms of positive reaction to SPT (p<0.001). However, the size of wheals produced was significantly less with rArt v 1 than nArt v 1 (p<0.05). Similar results were obtained for the nasal provocation test (difference in threshold levels, p<0.05) indicating low sensitivity and higher allergen requirement for rArt v 1 than nArt v 1 (15). This difference may be attributed to the involvement of carbohydrate-specific antibodies in epitope recognition (23).

Cross-reactivity

Art v 1 cannot play a role in identifying pollen-food-allergy syndrome as cross-reactive structures between food and mugwort pollens have not been found (23).

Compiled By

Author: Turacoz Healthcare Solutions

Reviewer: Dr. Fabio Iachetti

 

Last reviewed: December 2020

References
  1. Abuhadra MN, ; Mahklouf, M.H.; Essokne, R.S. A New Record Artemisia Vulgaris L. (Asteraceae) for the Flora of Libya. American journal of life science researches. 2017;5(3):83-8.
  2. Pablos I, Egger M, Vejvar E, Reichl V, Briza P, Zennaro D, et al. Similar Allergenicity to Different Artemisia Species Is a Consequence of Highly Cross-Reactive Art v 1-Like Molecules. Medicina (Kaunas). 2019;55(8):504.
  3. Hirschwehr R, Heppner C, Spitzauer S, Sperr WR, Valent P, Berger U, et al. Identification of common allergenic structures in mugwort and ragweed pollen. J Allergy Clin Immunol. 1998;101(2 Pt 1):196-206.
  4. Pointner L, Bethanis A, Thaler M, Traidl-Hoffmann C, Gilles S, Ferreira F, et al. Initiating pollen sensitization - complex source, complex mechanisms. Clin Transl Allergy. 2020;10:36.
  5. Ukleja-Sokolowska N, Gawronska-Ukleja E, Zbikowska-Gotz M, Bartuzi Z, Sokolowski L. Sunflower seed allergy. Int J Immunopathol Pharmacol. 2016;29(3):498-503.
  6. Heinzerling L, Frew AJ, Bindslev-Jensen C, Bonini S, Bousquet J, Bresciani M, et al. Standard skin prick testing and sensitization to inhalant allergens across Europe--a survey from the GALEN network. Allergy. 2005;60(10):1287-300.
  7. Deng S, Yin J. Mugwort Pollen-Related Food Allergy: Lipid Transfer Protein Sensitization and Correlation With the Severity of Allergic Reactions in a Chinese Population. Allergy Asthma Immunol Res. 2019a;11(1):116-28.
  8. Gadermaier G, Hauser M, Ferreira F. Allergens of weed pollen: an overview on recombinant and natural molecules. Methods. 2014;66(1):55-66.
  9. Himly M, Jahn-Schmid B, Dedic A, Kelemen P, Wopfner N, Altmann F, et al. Art v 1, the major allergen of mugwort pollen, is a modular glycoprotein with a defensin-like and a hydroxyproline-rich domain. FASEB J. 2003;17(1):106-8.
  10. Lombardero M, Garcia-Selles FJ, Polo F, Jimeno L, Chamorro MJ, Garcia-Casado G, et al. Prevalence of sensitization to Artemisia allergens Art v 1, Art v 3 and Art v 60 kDa. Cross-reactivity among Art v 3 and other relevant lipid-transfer protein allergens. Clin Exp Allergy. 2004;34(9):1415-21.
  11. Oberhuber C, Ma Y, Wopfner N, Gadermaier G, Dedic A, Niggemann B, et al. Prevalence of IgE-binding to Art v 1, Art v 4 and Amb a 1 in mugwort-allergic patients. Int Arch Allergy Immunol. 2008;145(2):94-101.
  12. Stemeseder T, Metz-Favre C, de Blay F, Pauli G, Gadermaier G. Do Plantago lanceolata Skin Prick Test-Positive Patients Display IgE to Genuine Plantain Pollen Allergens? Investigation of Pollen Allergic Patients from the North-East of France. Int Arch Allergy Immunol. 2018;177(2):97-106.
  13. Gao Z, Fu WY, Sun Y, Gao B, Wang HY, Liu M, et al. Artemisia pollen allergy in China: Component-resolved diagnosis reveals allergic asthma patients have significant multiple allergen sensitization. Allergy. 2019;74(2):284-93.
  14. WHO/IUIS. ALLERGEN NOMENCLATURE: WHO/IUIS Allergen Nomenclature Sub-Committee; 2020 [cited 2020 Nov 11 ]. Available from: http://www.allergen.org/search.php?allergenname=&allergensource=Artemisia+vulgaris&TaxSource=&TaxOrder=&foodallerg=all&bioname=.
  15. Schmid-Grendelmeier P, Holzmann D, Himly M, Weichel M, Tresch S, Ruckert B, et al. Native Art v 1 and recombinant Art v 1 are able to induce humoral and T cell-mediated in vitro and in vivo responses in mugwort allergy. J Allergy Clin Immunol. 2003;111(6):1328-36.
  16. Jahn-Schmid B, Fischer GF, Bohle B, Fae I, Gadermaier G, Dedic A, et al. Antigen presentation of the immunodominant T-cell epitope of the major mugwort pollen allergen, Art v 1, is associated with the expression of HLA-DRB1 *01. J Allergy Clin Immunol. 2005;115(2):399-404.
  17. Leonard R, Wopfner N, Pabst M, Stadlmann J, Petersen BO, Duus JO, et al. A new allergen from ragweed (Ambrosia artemisiifolia) with homology to art v 1 from mugwort. J Biol Chem. 2010;285(35):27192-200.
  18. Wopfner N, Gadermaier G, Egger M, Asero R, Ebner C, Jahn-Schmid B, et al. The spectrum of allergens in ragweed and mugwort pollen. Int Arch Allergy Immunol. 2005;138(4):337-46.
  19. Popescu FD. Cross-reactivity between aeroallergens and food allergens. World J Methodol. 2015;5(2):31-50.
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  21. Jahn-Schmid B, Kelemen P, Himly M, Bohle B, Fischer G, Ferreira F, et al. The T cell response to Art v 1, the major mugwort pollen allergen, is dominated by one epitope. J Immunol. 2002;169(10):6005-11.
  22. Knapp B, Fischer G, Van Hemelen D, Fae I, Maillere B, Ebner C, et al. Association of HLA-DR1 with the allergic response to the major mugwort pollen allergen: molecular background. BMC Immunol. 2012;13:43.
  23. Gruber P, Gadermaier G, Bauer R, Weiss R, Wagner S, Leonard R, et al. Role of the polypeptide backbone and post-translational modifications in cross-reactivity of Art v 1, the major mugwort pollen allergen. Biol Chem. 2009;390(5-6):445-51.