w6 Mugwort

Allergens within Weed Pollens

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  • Latin name: Artemisia vulgaris
  • Family: Asteraceae (Compositae)
  • Common names: Mugwort, Chrysanthemum Weed
  • Source material: Pollen
A weed species producing pollen, which often induces hayfever, asthma and conjunctivitis in sensitised individuals.

Allergen Exposure

Geographical distribution
Mugwort is native to Europe and Asia, but is now also found throughout the eastern US. It is rare, however, anywhere in the extreme north and south.
 
The plant is an aggressive, coarse perennial that spreads by persistent rhizomes. It generally reaches a metre or more in height, and has a rather untidy and unattractive appearance. The stem is downy, woody, grooved, and has a slight red tinge. The alternate, pinnate, deeply lobed leaves, 6 to 12 cm long and 3 to 9 cm wide, have a pleasant smell when bruised. The foliage resembles that of cultivated Chrysanthemum, but can be distinguished by the heavy covering of white/light-gray woolly hairs on the lower leaf surface. Juvenile Mugwort can be confused with Ragweed, but the latter has more finely cut leaves. Mugwort also has a basal rosette of leaves that survives most winters.
 
Small, greenish-yellow to red-brown flower heads appear from summer to mid-autumn in clusters at the top of the plant, and produce tiny, inconspicuous yellowish-green flowers. The flowers are hermaphrodite (have both male and female organs) and are pollinated by wind.
 
The fruit is an achene that encloses the seed; however, viable seeds are rarely produced in North America. Seedlings are rarely encountered in the northeastern US. In the southeastern US, where seeds are spread by floods, seedlings are more common.
 
Environment
Mugwort is most common on rubbish heaps, roadsides, sites of demolished buildings in towns, and a variety of other disturbed situations. It is a problem weed in turf grass, nurseries, and natural areas; but is rarely encountered in cultivated fields. But once introduced to a landscape, Mugwort is difficult to control, spreading by cultivation acivities and encroaching on adjacent areas via rhizomes. It has been grown as an ornamental and a medicinal herb.
 
Allergens
  • Art v 1, a 47 kDa protein (1)
  • Art v 2, a 34 - 38 kDa glycoprotein (2, 3) 
  • Art v 3, a 10 kD lipid transfer protein (7)
Art v 1 binds to at least 70% of the sera of individuals allergic to Mugwort pollen (1).
Art v 2 was shown to be antigenically identical with the allergen formerly isolated by Nilsen et al. and denoted Ag7 (4). Art v 2 bound IgE from 5 (33%) of 15 sera from patients with clinical allergy against Mugwort pollen and from 13 (52%) of 25 sera from patients selected only on the basis of a RAST-class 4 against Mugwort pollen (3).
 
In addition to the characterised allergens, Mugwort has been shown to contain many other allergens that will require further elaboration. Caballero et al. demonstrated that Mugwort pollen contained 9 allergens ranging from <16 to 65 kDa in size(5). Nilsen et al. isolated 15 components with molecular weights of 12 kDa -100 kDa, which bound IgE from sera from 16 Mugwort allergic patients. A 22 kDa component bound IgE from at least 94% of the sera tested. Five other components of 12, 17, 29, 39 and 42 kDa bound IgE from 75-94% of the patient sera. Ag 12 was shown to be a 22 kDa protein, and Ag 13 a 61 kDa protein (6).
 
Art v 3, a Lipid Transfer Protein, 9,7 kDa in size, and with a 43-50% sequence identity with the equivalent allergens of Apple, Peach and Chestnut, has been isolated (7).
 
A Profilin has also been isolated (8). 

Potential Cross-Reactivity

An extensive cross-reactivity among the different individual species of the genus could be expected, as well as to a large degree among members of the family Asteraceae (Compositae) (9-10). This has been confirmed by in vitro and in vivo studies. Strong in vitro cross-reactivity was demonstrated between nine Artemisia species: A. frigida, A. annua, A. biennis, A. filifolia, A. tridentata, A. californica, A. gnaphalodes, A. ludoviciana, and A. vulgaris. Electrophoretic studies showed a great deal of similarity in the bands among the 9 species, and nitrocellulose blots showed similar IgE binding patterns (11). Cross-reactivity was demonstrated between Sunflower and other Asteraceae (Compositae) pollens (Mugwort, Marguerite, Dandelion, Golden Rod, Short Ragweed, and Chrysanthemum). Mugwort pollen exhibited the greatest degree of allergenic homology with Sunflower pollen, whereas at the other end of the spectrum, Short Ragweed showed fewer cross-reactive epitopes (12-13). Cross-reactivity has also been shown between Camomile-tea extract and pollen from Matricaria chamomilla (Camomile), Ambrosia trifida (Giant Ragweed), and Artemisia vulgaris (Mugwort) (14-16). Studies have also demonstrated allergen similarity between Lettuce (Lactuca sativa) and Mugwort, both members of the same family (17).
 
The association between Mugwort and Ragweed pollens will require further studies for exact clarification; an earlier study indicated that there was no cross-antigenicity between Mugwort and Ragweed pollens (18). By contrast, it has been reported that despite the rare occurrence of Ragweed in Middle Europe, a surprisingly high number of patients allergic to Mugwort, a frequently encountered weed, displayed IgE reactivity against Ragweed pollen allergens. By using recombinant Birch profilin and specific antisera for IgE inhibition experiments, profilin was identified as one of the cross-reactive components in Mugwort and Ragweed pollen. In addition to profilin, Mugwort and Ragweed pollen contain a number of cross-reactive allergens, among them the major Mugwort allergen Art v 1. Cross-reactive IgE antibodies can lead to clinically significant allergic reactions (19).

Furthermore, Mugwort, Ragweed, and Timothy grass pollen share IgE epitopes with glycoprotein Latex allergens, which confirms the probable cross-allergenicity between Mugwort and Ragweed, and the presence of common epitopes might in part explain clinical symptoms in patients allergic to pollen on contact with Latex (20).
 
Extensive cross-sensitisation has been reported between pollen from flower plants of this family and pollen of the Amaryllidaceae family (Alstroemeria and Narcissus). The authors suggest that Mugwort can be used as a screening test for possible flower allergy (13).
 
Cross-reactivity between Celery and Birch pollen occurs to a greater extent in Central Europe than Southern Europe, where cross-reactivity between Celery and Mugwort predominates (21). Cross-reactivity has also been demonstrated to be common between Mugwort, Celery, Carrot and spices from the Apiaceae family (Anise, Fennel, Coriander and Cumin extracts) (Celery-Carrot-Mugwort-Spice syndrome) (22-24).   
 
No panallergen has yet been identified for the Celery/Mugwort/Carrot/Spice association although various panallergens may be involved in some associations (25). Three groups of proteins have been identified as responsible for cross-reactivity between Celery and Birch pollen and were shown to be homologues of Bet v 1 and Birch profilin (Bet v 2). Although two of these groups of allergens (profilin and the 46 to 60 kDa proteins) were also present in Mugwort pollen, they were not solely responsible for the cross-reactivity between Celery and Mugwort (8, 26-27).  
 
Leitner et al. concluded that IgE cross-reactivity in the Mugwort-Birch-Celery-Spice syndrome to the spices Pepper and Paprika was not caused by homologues of Bet v 1 and profilin (28).
 
IgE binding to all 3 structures in Celeriac extract (Celery) was inhibited by Birch pollen extract, whereas Mugwort pollen extract could only inhibit IgE reactivity to Celery allergens, Api g 4 and common carbohydrate determinants (CCD) (29). Cross-reactivity has also been demonstrated between Mango, Mugwort pollen, Birch pollen, Celery and Carrot by EAST inhibition and immunoblot inhibition studies. The authors suggest that these are due to Bet v 1 and Art v 1, the major allergens of Birch and Mugwort pollen, respectively (30).
 
Additionally, an association between Mugwort pollinosis and sensitisation to Celery, Carrot, Spices, Nuts, Mustard and Leguminoseae vegetables has been reported (31). The existence of common antigenic epitopes in Pistachio and Mugwort pollen was demonstrated in a Mugwort-allergic patient (32).
 
Profilin will result in varying degrees of cross-reactivity between Mugwort and other pollen and food containing this panallergen. Profilin is found in Apple, Celery, Carrot and pollen from Birch, Bermuda grass (Cynodon dactylon), Johnson grass (Sorghum halopense), Meadow grass (Poa pratensis), and Short Ragweed (Ambrosia elatior) (33-36). Mugwort also cross-reacts with Poppy seed extract due to cross-reacting homologues of pollen allergens including Bet v 1 and profilin (37). Mugwort also cross-reacts with Kiwi, probably as a result of the profilin panallergen (38).
 
The Lipid Transfer Protein from Artemisia pollen could be expected to cross-react with LTPs from other plants. LTP from Mugwort and from Chestnut seed showed 43-50% sequence identity with the equivalent allergens of Apple and Peach in the first 30 N-terminal residues. A similar degree of sequence identity (50%) was found between the Artemisia and Chestnut proteins. Both isolated LTPs bound specific IgE of sera from Rosaceae fruit-allergic patients (7).
 
Bet v 4, a calcium-binding protein from Birch pollen, was able to drastically reduce IgE binding to proteins of similar molecular weight in pollen extracts from distantly related plant species (e.g. Timothy grass, Mugwort, Lily), but not in extracts from plant-derived foodstuffs (39).
 
Annual Mercury (Mercurialis annua) pollen sensitisation is prominent in several areas of Spain. A significant but low-antigenic cross-reactivity between Mercurialis annua and Olive tree (Olea europaea), Ash tree (Fraxinus elatior), Castor bean (Ricinus communis), Saltwort (Salsola kali), Wall Pellitory (Parietaria judaica) and Mugwort was demonstrated by several in vitro techniques (40).
 
A monoclonal antibody raised against the high molecular-weight major Mugwort pollen allergen Art v 1 cross-reacted with moieties of comparable molecular weights in Birch and Timothy grass pollen, as well as in Apple and Celery extracts indicating the presence of Art v 1 homologues in the other species (41). 
 
IgE binding to Ginkgo pollen was inhibited by more than 80% by Mugwort (and Oak, Ryegrass, and Ragweed). The panallergen Bet v 2 (profiling) does not appear to be responsible (42). 
 
A high inhibition of IgE binding of Olive pollen extract was exhibited by Birch, Mugwort, Pine, and Cypress pollens, suggesting that these extracts contain proteins which share common epitopes and thus can be recognized by Olive-allergic patients (43).
 
CAP inhibition experiments demonstrated that Tobacco, Mugwort pollen, and Tomato extracts inhibited the binding of IgE antibodies from a tobacco-allergic patient's serum to solid-phase tobacco leaf. Tobacco (Solanaceae family) is often used as a contact insecticide in gardens (44).
 
In a pool of 28 individual sera with specific IgE to Mugwort pollen and Hazelnut, RAST to Hazelnut was inhibited up to 63% by Mugwort pollen, but the Mugwort pollen Specific IgE binding was only inhibited up to 36% by Hazelnut. In the SDS-PAGE immunoblotting inhibition Hazelnut partially inhibited all the Mugwort pollen bands, except that with 19kDa, whereas Mugwort pollen produced a nearly total inhibition of all the Hazelnut allergens. In the isoelectrofocusing immunoblotting inhibition Hazelnut produced a partial inhibition of all the bands of Mugwort pollen and Mugwort pollen partially inhibited all the allergenic bands of Hazelnut (5).

Clinical Experience

IgE mediated reactions
Mugwort sensitisation and allergy has been reported widely. Mugwort pollen is a major cause of asthma, allergic rhinitis, and allergic conjunctivitis. Exposure to Mugwort pollen contributes to the causation or exacerbation of the Oral Allergy Syndrome, eczema, urticaria; and anaphylaxis where pollen has contaminated a food, e.g., honey (15, 32, 45-47). 
 
Approximately 25% of Mugwort-allergic patients have reported subsequent hypersensitivity to a variety of foods: (in decreasing order) Honey, Sunflower seeds, Camomile, Pistachio, Hazelnut, Lettuce, Beer, Almond, Peanut, other nuts, Carrot, and Apple (32).
 
The measurement of specific IgE in blood has been reported to be a very useful test for determining sensitisation to Mugwort for epidemiologic studies of inhalant allergic diseases and for mass screening programs (48).
 
Mugwort is an important cause of sensitisation and allergy in Germany (49). A total of 1235 children aged 5-6 years from two West and five East German locations were examined by specific IgE tests to a panel of inhaled and oral allergens. Twenty-three percent exhibited at least one positive reaction, and the prevalence of sensitisation to Mugwort pollen was found to be 4.5% (50). Exacerbation of eczema after contact with Mugwort pollen was reported by 10% of patients with sensitisation (47).
 
Mugwort has also been reported as an emerging aeroallergen in Italy, with sensitisation prevalence increasing (51-52). In a study of respiratory allergens in atopic asthmatic children in the Chieti-Pescara area, 17% of 507 patients were positive on specific IgE determination to Mugwort (53). Similar findings were reported in another study. Pollen allergy to Parietaria was found to be present in 82.02% of pollen-allergic patients, followed by Gramineae (32.12%), Olea (23.11%), and Mugwort (17.08%). The authors point out that pollinosis differs in northern Italy, the northern Mediterranean area, and the southern coast of France, where allergic sensitisation to Poaceae is the most important (54).
 
The prevalence of sensitisation to Mugwort has also increased in France (55). In the north of France, where no Ragweed grows, Mugwort was reported to be the third most important cause for pollinosis in children after grasses and Plantago. Specific IgE determination in 184 children with allergic symptoms during summer was positive in 21%. Of these, 2 were less than 5 years in age. None of this group were food-allergic (56).
 
In the central part of Switzerland, pollinosis is mainly caused by pollens of Birch, Alder, Hazel, and Ash trees, and by pollen of grasses and Mugwort. The pollen levels were reported to be highly dependent on geographic and climatic conditions and therefore to vary considerably between different regions in Switzerland (57-58). In 229 predominantly adult patients who demonstrated an immediate-type allergy to one or more specific foods at the Allergy Unit, Zurich University Hospital, 53.3% were also affected by pollinosis. Cross-reactivity between food allergy and Birch or Mugwort pollen was demonstrated by many patients (59).
 
A study conducted in Murcia, in Spain, reported that 3 consecutive pollen seasons of Artemisia occur each year, related to three different species (A. campestris, A. herba-alba and A. barrelieri), and that winter blooming of Artemisia could explain the incidence of subsequent pollinosis in the Murcia area. The Artemisia species are highly cross-reactive: hence, this study is relevant from the perspective of cross-reactivity to Mugwort (60). In Salamanca, Mugwort was detected in aerobiological studies, although not found to be one of the most abundant taxa (61). In contrast, Artemisia pollen levels recorded in the Iberian Peninsula were the highest recorded in Spain (62).
 
Mugwort pollen is an important aeroallergen in Poland (45, 63). In an examination of the records of 8,576 patients with upper airway allergy, hypersensitivity to weed pollen allergens was found in 12.5%. The most prevalent sensitisation was to Wormwood (86.2%), followed by Mugwort (82.9%) (64).  In another study, of 446 patients with pollinosis, 42% were sensitised to Mugwort. In 71% of these, the clinical symptoms appeared only after the age of 20. In half of these patients, the clinical symptoms were not only seasonal but also perennial. Approximately 25% of this group were affected by allergic skin reactions. Eighty percent of Mugwort-sensitised patients were also sensitised to pollen from other Compositae plants (65). 
 
In south Hungary, of 642 patients with seasonal allergic rhinitis, 261 underwent specific IgE tests for common allergens, demonstrating that sensitisation had occurred to Poaceae in 84%, Secale in 63%, Ragweed in 63%, and Mugwort in 33% (66).
 
Mugwort pollen sensitisation has also been reported from Sweden and Finland (67-68). In a Swedish study, involving specific IgE tests performed on 7099 adult patients with asthma and/or rhinitis, the proportion of positive tests for Mugwort demonstrated that during a 12-year period, from 1981 to 1992, sensitisation to Mugwort showed a decrease, as compared to other pollen allergens (67).
 
In central Turkey, 24% of 100 patients with allergic rhinitis and/or asthma were reported to be sensitised to Mugwort (69). A second study of 1149 patients diagnosed with asthma from five major cities (Ankara, Izmir, Samsun, Elazig, and Adana), reported that the spectrum of allergen sensitisation included House Dust Mite, pollens, Cockroach, pet animals, and molds in decreasing order of frequency. Phleum pratense (Timothy) and Artemisia vulgaris (Mugwort) were the most common pollens in all regions (70).
 
Mugwort sensitisation has also been reported from Japan (71-72). In Hokkaido, positive specific IgE in 379 subjects to Artemisia was recorded in 16.9% (73). In 107 patients with nasal allergies in Sapporo, specific IgE was positive for Timothy grass in 22.4%, in 14.0% for Birch and in 12.1% for Mugwort (74).
 
Mugwort and Ragweed pollens have been considered to be important respiratory allergens in Korea. These two pollens are abundant in the air of Seoul from August through October (18).
 
Mugwort is a common weed and an important source of allergens on the subtropical island of Tenerife, in the Canary Islands. It pollinates mainly from July to September, although, due to some local climatic conditions, it may flower throughout the year. Cross-reactivity with Hazelnut, Kiwi, Birch, several Compositae (Ambrosia, Chrysanthemum, Matricaria, Solidago) and grass allergens has been suggested (15, 75-76). 
 
Two patients sensitised to Mugwort pollen who experienced severe systemic reactions (anaphylaxis and generalized urticaria/angioedema) due to ingesting honey and royal jelly containing this pollen were reported (77). Anaphylaxis was reported in a 32-year-old atopic patient following the ingestion of a pollen compound prepared at an herbalist's. A few minutes after ingestion, generalized pruritus, diffuse erythema, facial oedema, cough, hoarseness and dysphonia occurred. Analysis of the compound recorded the presence of Taraxacum officinalis (15%), Artemisia vulgaris (5%) and Salix alba (15%) pollens (78).
 
Other reactions
Artemisia vulgaris is widely used in the Philippines for its anti-inflammatory properties (79).

Compiled by Dr Harris Steinman, harris@zingsolutions.com

References:

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