w233 Art v 3

Summary

Art v 3 is a nonspecific lipid transfer protein (nsLTP) from mugwort (Artemisia vulgaris) pollen, cross-reactive with food and pollen homologues, including Pru p 3 from peach. Art v 3 sensitization is associated with increased prevalence of severe respiratory symptoms in patients with A. vulgaris pollinosis patients, and with nsLTP allergy and food-induced reactions with or without A. vulgaris pollinosis.

Epidemiology

Worldwide distribution

A. vulgaris pollen is a major cause of weed pollinosis in Europe, North America, and China  [1-3]. Among the six A. vulgaris allergens present in the IUIS/WHO database, Art v 3 is a nsLTP sharing partial cross-reactivity with Pru p 3 [1, 4].

Art v 3 sensitization is observed in association to sensitization or allergy to nsLTP and/or to A. vulgaris pollen [5, 6]. First considered an allergen typical of Mediterranean areas, Art v 3 has since been convincingly demonstrated as part of the nsLTP syndrome irrespective of the geographical area [7].

Art v 3 was described as an A. vulgaris pollen nsLTP binding IgE from Mediterranean peach and apple allergic patients, with partial cross-reactivity to other food and pollen nsLTP [8]. Art v 3 prevalence was reported at 34.4% in Mediterranean peach allergic patients with A. vulgaris sensitization [6] and at 100% in Chinese patients allergic to peach and mugwort [3]. In Mediterranean mugwort-allergic patients without fruit allergy, Art v 3 sensitization was initially reported as lacking [5], however, it was subsequently demonstrated in a substantial number of such patients, 40% [6] or even 83% [9]. A prevalence of 38.7% (12/31) was reported in Chinese patients with A. vulgaris pollinosis but not affected by peach or other plant food allergy [3], however, figures vary according to the clinical presentation of A. vulgaris pollinosis [10].

Outside the Mediterranean area, Art v 3 sensitization was reported in 100% of Chinese patients with A. vulgaris pollinosis and peach allergy [3], in 60% of UK patients with proven nsLTP allergy [11], in 34% of Belgian pollen or food allergic patients [12], and in only 4.6% of pollen-sensitized Czech patients with physician-diagnosed allergy or atopy [13]. Levels of Art v 3 IgE were correlated to those of Pru p 3 IgE in nsLTP allergic or sensitized patients from China, the United Kingdom, and Belgium [11, 12, 14].

In Art v 3 sensitized subjects, concomitant sensitization to the defensin Art v 1 confirms genuine sensitization to A. vulgaris pollen, while the lack of detectable Art v 1 sensitization, supplanted by sensitization to nsLTPs, suggests cross-sensitization from nsLTPs, such as Pru p 3 [7, 13].

Overall, Art v 3 prevalence varies according to the study population, with a usual range of 22% to 70% [1].

Art v 3 as a monosensitization among a large panel of food and pollen allergens was not observed in a Central European cohort [13]. Art v 3 IgE can be detected in patients with negative skin prick tests to A. vulgaris extract [6]. 

Environmental Characteristics

Source and tissue

Art v 3 is mainly present in A. vulgaris pollen [8], associated with the cell wall, with small amounts also detectable in the cytoplasm [15].

Risk factors

The main risk factor for developing sensitization to Art v 3 is exposure to A. vulgaris pollen  [4, 6] Cross-reactivity from other nsLTP is also possible [7, 11, 13].

Clinical Relevance

Detailed information regarding A. vulgaris pollinosis, which manifests itself mainly as allergic rhinitis, rhinoconjunctivitis and asthma, is available in the whole allergen section. 

Disease severity and prediction

In patients with doctor-diagnosed A. vulgaris pollinosis, asthma was associated with higher prevalence and higher levels of Art v 3 IgE [10]. Nasal provocation test with A. vulgaris extract induced rhinitis symptoms in Art v 3 monosensitized patients, thus confirming the clinical relevance of Art v 3 IgE in pollinosis [16].

In patients with plant food allergy, Art v 3 sensitization is a marker of nsLTP allergy [7] and as such, it is associated with more severe symptoms upon reaction to culprit foods [14].

Conversely, Art v 3 sensitization in patients without reactions to food has not been firmly established as a marker of A. vulgaris pollinosis, due to conflicting reports [7] and also because the pollination season of A. vulgaris usually overlaps with that of other, cross-reactive weeds [2].

In Chinese and Spanish patients with A. vulgaris pollinosis, Art v 3 sensitization has been proposed to arise as a result of exposure to extremely high levels of airborne pollen, secondarily resulting in nsLTP-related plant food allergy [3, 9, 14].

Cross-reactive molecules

Art v 3 shares clinically relevant cross-reactivity with other pollen and food nsLTPs such as Pru p 3 [7], and is now considered as an allergen associated to nsLTP syndrome. 

Molecular Aspects

Biochemistry

Art v 3 has a molecular weight of 12 kDa [4] and belongs to the nsLTP panallergen family of monomeric, non-glycosylated proteins with a globular conformation comprising four alpha helices stabilized by four disulfide bonds, conferring resistance to heating and acidic pH [1, 17]

Isoforms, epitopes, antibodies

As of December 30th, 2021, four isoallergens of Art v 3 have been included in the World Health Organization (WHO) and International Union of Immunological Societies (IUIS) Allergen Nomenclature [4].

Cross-reactivity due to structural similarity

Art v 3 shares clinically relevant cross-reactivity with Pru p 3 and other food and pollen nsLTPs [7]. At the molecular level, structural alignment of Art v3 and other nsLTPs showed higher similarity than sequence alignment, with similar folding, conserved disulfide bonds and a similar ligand-binding hydrophobic cavity [17]. 

Diagnostic Relevance

Marker allergen for complex sensitization profiles to A. vulgaris pollen

Patients with A. vulgaris pollinosis living in areas with high exposure to this pollen exhibit more complex sensitization profiles, including more frequent Art v 3 sensitization, which is associated with an increased prevalence of asthma [10]. 

Marker allergen for nsLTP panallergen sensitization

As soon as Art v 3 was identified, it was associated with an increased prevalence of plant food reactions [8]. Subsequent studies showed that Art v 3 sensitization is present in nsLTP allergic patients with or without A. vulgaris pollinosis or even pollen exposure [7]. Art v 3 may act as the primary sensitizer in patients with A. vulgaris pollinosis following exposure to very high levels of airborne mugwort pollen, leading to nsLTP allergy categorization as a pollen-food syndrome [7, 10, 14]. However, the causal link between A. vulgaris pollinosis and nsLTP allergy manifested as plant food allergy is a matter of debate in most geographical regions [7].

Besides Art v 3, plant food reactions associated with A. vulgaris sensitization may involve other cross-reactive allergens, e.g. defensin [18], hence requiring careful investigation.

Cross-Reactivity

Art v 3 displays clinically relevant cross-reactivity with other pollen and food nsLTPs [7, 17], except from Parietaria judaica (wall pellitory) [9]. Homology between Art v 3 and its pollen homologues from Artemisia species other than A. vulgaris make it suitable for investigating subjects sensitized to different Artemisia pollen [19]. 

Exposure

The main route of exposure is through inhalation of A. vulgaris pollen, especially at high levels of exposure [1, 4, 10]. An alternative mechanism has been suggested via Pru p 3 sensitization, independent of pollen inhalation [7].

Compiled By

Author: Joana Vitte

Reviewer: Dr. Christian  Fischer

Last reviewed:February 2022