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w6 Mugwort

Mugwort
Code w6
Family Asteraceae (Compositae)
Source Material Pollen
Latin Name Artemisia vulgaris
Common Name Mugwort, Chrysanthemum Weed, Common Wormwood
Categories Weed Pollens

Summary

Mugwort (Artemisia vulgaris), belonging to the family Asteraceae or Compositae, is a perennial root stalk weed that grows along the roadsides, in waste area and infests nursey crops. It is found troublesome in about 25 crops in 56 countries. Mugwort is distributed widely across Europe, Canada, United States and parts of Asia. Mugwort is usually wind-pollinated and inhalation of the pollen grains (spheroidal in shape) is responsible for its allergic reactions. The prevalence of its allergy has been found in several parts of Europe as well as parts of Asia, especially China and Korea. Mugwort pollens are known to trigger type 1 allergic reactions like allergic rhinitis, conjunctivitis and asthma. Besides this, mugwort is also linked with plant-derived food allergies (pollen-food-allergy syndrome). It is clinically manifested as oral allergy syndrome, angioedema, urticaria or even anaphylaxis. The mugwort proteins, namely Art v 1, Art v 2, Art v 3, Art v 4, Art v 5 and Art v 6 have been identified as having allergenic potential. Mugwort and ragweed pollens show high level of cross-reactivity since they are related weeds. Further, mugwort also cross-reacts with many food allergies leading to pollen-food allergy syndrome like mugwort-celery-spice, mugwort-fennel, mugwort-mustard, mugwort-peach, mugwort-sunflower syndrome etc.

Allergen

Nature

Artemisia vulgaris (mugwort) is a perennial weed that grows by giving rise to lateral shoots and adventitious roots. The stem is 70-150 cm tall, erect, ribbed, branched, and reddish. Mugwort is characterized by broad dark green leaves that are smooth on the upper side and bear densely matted, white, wooly hair on the lower side (1-3). The leaves are stalked alternately with lobes arranged on either side of a central axis (pinnate). The axis bears flowers in groups, varying from reddish brown to yellowish in color (1). The flowering season of mugwort varies between May and October, depending on the geographical location (4-6).

Differences in morphological and physiological characteristics of mugwort have been reported in different geographical regions. In the Himalayan region, the diploids grow as small herbs; the tetraploids with a shrubby base and a herbaceous apex while the hexaploids form large shrubs. Also, there is a significant variation in the size and shape of leaves from one mugwort plant to another, which is usually not seen in other similar species (3).

In many parts of Asia, mugwort is regarded as an edible herb (7, 8). In China, mugwort has medicinal uses owing to its antioxidant, anti-inflammatory, anticancer, hypolipidemic, antimicrobial, and antidiabetic properties (8).

Taxonomy

Mugwort belongs to Asteraceae family of plants (7). It is often confused with other species of Artemisia (A. absinthium, A. annua, A. ludoviciana and A. tridentata) as well as ragweed (Ambrosia artemisiifolia L.) and cultivated chrysanthemum (Chrysanthemum spp.)  because of the high resemblance between them. However, it can be distinguished from them by the presence of silvery-white wooly hairs only on the lower surface of its leaves (9).

Taxonomic tree of  Mugwort  (10,11)  
Domain Eukaryota
Kingdom Plantae
Phylum Spermatophyta
Subphylum Angiospermae
Class Dicotyledonae 
Family Asteraceae
Genus Artemisia
Species Artemisia vulgaris

 

Tissue

The pollen grain of mugwort is spheroidal in shape (sometimes slightly elongated or flattened). Their diameter varies between 20-23 μm. The grains have three grooves, the intended furrows measuring approximately 10μm and pores measuring 5.0 μm. A thick outer covering (1μm, 2.4μm at equator and 1.6μm at the poles) of the pollen grain gives it a scalloped form. The surface is covered with very short, blunt spines (0.5μm in length) that are nearly 1μm apart from one another. The inner layer of the pollen grain lacks the sculptured characteristic of the outer layer with a thickness of approximately 1μm (6).

Epidemiology

Worldwide distribution

Mugwort is one of the most significant members of the Asteraceae or Compositae family (12). In Europe, pollen from mugwort is among the principal causes of allergy and sensitization rates among suspected allergy patients have been shown to vary between 15 % (Northern Europe) and 10 % (Southern Europe) (13).

In Germany, mugwort is one of the most significant weeds causing pollinosis (14). In a prospective study conducted in Northern Spain, 36% of 72 patients having IgE-mediated allergic reactions to plant foods were found to be mugwort pollen sensitized (15).  In a cohort of 29 rhino-conjunctivitis patients in Strasbourg, France, 55.2% were sensitized to mugwort pollen extracts (16). In a cross-sectional study in Southern Italy, 16.7% of 350 adolescents (14 to 18 years) with respiratory allergy in the form of asthma and/or rhinitis, were sensitized to mugwort (17). Further, in a prospective follow-up study on 401 Italian children with a history of seasonal allergic rhino-conjunctivitis (SAR), sensitization to mugwort was found to be significantly reduced (p=0.009) from 27.2% at baseline (2009-2011) to 20.7% (2015-2017) (18).

In China, mugwort pollen is among the leading causes of rhino-conjunctivitis and asthma during late summers and autumn (19, 20). In another Chinese study, 402 patients with seasonal pollinosis (allergic rhinitis, bronchial asthma, or allergic conjunctivitis) were categorized into three groups: Spring, Autumn, and Combined Season group. Mugwort was the major allergic source in 94% (n=63) of the Autumn Symptom group and in 85% (n=302) of the Combined Season group (22). Mugwort pollinosis is also common in Korea (23).

Risk factors

The pollination season for mugwort is primarily between the end of summer and the beginning of autumn when patients sensitized to mugwort experience allergic reactions, especially in Europe and China (7, 19, 20).

Environmental Characteristics

Living environment

Mugwort is a perennial rootstalk weed that spreads rapidly (9) and mostly prefers moist soil (3). It can tolerate an extensive range of temperatures ranging from cold Northern Himalayan areas to South America's warm temperate regions (2).

In the Eastern parts of the United States and Canada, mugwort grows along the sides of the roads, urban landscapes, in waste areas, and infests nursery crops (2, 3). 

Worldwide distribution

Mugwort was a native to Russia but now widely distributed across Europe, North and South America, parts of Asia, and even Australia (2-4, 7). It survives in the temperate, humid regions of the Northern hemisphere and the Mediterranean basin (5).

It is also commonly found in Eastern Canada and the United States. This weed is commonly reported to affect 25 crops in 56 countries. Mugwort is not found in only two continents: Africa and Antarctica (3). However, it has been recently reported in Libya, a country in North Africa (2).

Route of Exposure

Main

Mugwort is wind-pollinated and inhalation of the pollen grains or pollen grain fractions is the main route of exposure. Pollen grains from mugwort enter the body through the upper respiratory tract, the mucosa of oral cavity and the eyes (24).

Detection

Pollen is among the leading causes of allergic conjunctivitis, allergic rhinitis (AR), and bronchial asthma (22). Mugwort pollens are known to trigger type 1 allergic reactions like allergic rhinitis, conjunctivitis, and asthma  (25-28). In Europe, pollen from mugwort is among the principal causes of allergy. The sensitization rates among suspected allergy patients for AR varies between 15 % (Northern Europe) and 10 % (Southern Europe) (12).

Apart from specific symptoms (like rhino-conjunctivitis and asthma), pollen allergies also cause sleep disorders, fatigue, depression, and impaired cognition in allergic patients. These symptoms increase during pollen season and decrease the quality of life in allergic patients (29, 30).

Allergic rhinitis

Allergic rhinitis was reported in 95% (n=240) and conjunctivitis in 53% (n=126) of patients with a positive history or specific IgE tests to mugwort in a study in China. (21). Among 401 Italian children (mean age- 10.4 ± 3.4 years at baseline) with a history of seasonal allergic rhino conjunctivitis (SAR), AR was found in all (100%) of them at baseline and 93.3% (n=374) patients (mean age- 16.2 ± 3.6 years) at follow-up. Out of these, 27.2% were found to be allergic to mugwort at baseline, which decreased to 20.7% at follow-up. The patients also presented with oral itching with or without lip and/or tongue angioedema [Oral allergy syndrome (OAS)] after food ingestion, at baseline. At follow-up, food‐related allergic symptoms, particularly urticaria/angioedema and gastrointestinal symptoms were found to be increased (18). Out of 402 adult Chinese AR patients (mean age of 30.4 ±14.1 years), mugwort was found to be the primary allergic source affecting 94% (n=63) patients in the autumn season and 85% (n=302) patients in both spring and autumn season. Pollen-related food allergy was seen in 30% (n=119) of the study population; fruits were the most common food items triggering pollen-related food allergy (22).

Asthma

Exposure to mugwort pollen triggers asthma in mugwort sensitized patients (26). Out of a total of 240 Chinese patients allergic to Artemisia pollen who had either positive history or specific IgE tests to mugwort, 43% (104) patients exhibited allergic asthma. Patients with allergic asthma presented with a history of dyspnea, wheezing, and/or episodes of cough. The most commonly identified allergen was Art v 1 (53-93%), followed by Art v 3 9-66%) and Art v 2 (9-48%). It was suggested that sensitization to three or more allergens of mugwort caused a greater risk for allergic asthma (21).

Atopic Dermatitis

In the Chinese population, atopic eczema was observed in 19% (45) patients out of a total of 240 patients who had either positive history or specific IgE tests to mugwort. Patients presented skin rash with red, raised itchy bumps (21).

Other diseases

Pollen-food allergy syndrome

Plant-derived food allergies are frequently linked with pollen allergens, which act as prima­ry sensitizers (31). Pollen-food-allergy syndrome (PFAS) is also reported in mugwort-sensitive patients but less than birch pollen-sensitized individuals (32, 33). These allergic reactions in addition to mugwort-pollen allergy are expressed as oral allergy syndrome (OAS), angioedema, urticaria, and/or anaphylaxis (19, 34). Lipid Transfer Proteins (LTPs) are found responsible for mugwort-PFAS that is reported in China as well as Korea (19, 35).

The mugwort association with several food items has been reported like mugwort-celery-spice, celery-mugwort-birch-spice, mugwort-fennel, mugwort-peach, mugwort-mustard and mugwort-chamomile syndrome (6, 34). The association of mugwort has also been observed with apple, mango, peanut, and hazelnuts (19). However, the incidence, clinical symptoms, and sensitization profiles of these food allergies might vary from one region to another (19).

In China, mugwort is the primary allergen associated with LTP-related PFAS (19). A study involving 148 mugwort pollinosis patients reported food allergies in 72% of patients. The clinical manifestations included OAS (68%, n=73), urticaria (51%, n=55), respiratory symptoms (37%, n=40), gastrointestinal symptoms (35%, n=37), hypotension (11%, n=12) and even anaphylaxis (48%, n=51). Further, the most common food responsible for allergic reactions in 107 PFAS patients were peaches (64%) followed by apples (24%), mangos (20%), peanuts (16%) and hazelnuts (14%) (19). Further, in another study in China conducted on 119 PFAS patients, mugwort allergy was found in 31/33 patients with food-induced anaphylaxis (22). Further another study in China reported peach allergy to be co-existing in 55% of 69 mugwort pollen-allergic patients (20).

Molecular Aspects

Allergenic molecules

Till date, six allergenic molecules have been identified and characterized and published officially by World Health Organization/International Union of Immunological Studies (WHO/IUIS) Allergen Nomenclature Sub-Committee for mugwort. The table below provides detailed information on each of the allergenic protein (32, 36):

Allergen Biochemical Name  Molecular Weight (kDa) Allergenicity
Art v 1 Defensin-like protein linked to polyproline-rich region 24-28
  • Major mugwort pollen allergen (37).
  • Sensitization prevalence of more than 95% in mugwort-allergic patients (32, 38).
  • Specific IgE reactivity on ELISA assay was found in 79% (nArt v 1) and 39% (rArt v 1) of 100 mugwort-allergic European children (4).
  • Sensitization of 53-93% was found in 240 mugwort-allergic Chinese patients (21).
  • Shows some cross-reactivity with Amb a 4 (ragweed) (37).
Art v 2 Pathogenesis-related protein PR-1

35

  • Sensitization prevalence of 57.9% and 63.2% in skin prick and enzyme-allergosorbent assays was found respectively (32).
  • Sensitization of 9-48% was found in 240 mugwort-allergic Chinese patients (21). 
Art v 3 Non-specific lipid transfer protein type 1

12

  • Sensitization predominantly high (70%) in the Mediterranean regions (32).
  • Sensitization of 9-66% was found 240 mugwort-allergic Chinese patients (21).
  • Variable presence in different mugwort-pollen-allergic patients (32).
  • Shows some cross-reactivity and 50% sequence identity with Pru p 3 (peach allergen) (39).
Art v 4 Profilin 14
  • Specific IgE-binding on dot-blots was found in 26% of 246 mugwort and ragweed allergic European patients (40).
  • Reactivity on ELISA immunoblots was found in 26% of 26 mugwort sensitized patients’ sera (age: 8-72 years) (41) while 34% of 100 pediatric mugwort-allergic patients (4).
  • Amb a 8 (ragweed) reported sequence identity of 89% (41).
  • Involved in pollen-food-allergy syndrome like celery-mugwort-spice, mugwort-peach, and mugwort-mustard syndrome. (34). 
Art v 5 Polcalcin

9

  • Type of calcium-binding protein (CBP) (40)
  • Approximately 10% of 45 and 25-30% of 42 mugwort and ragweed allergic patients from Austria and Italy respectively showed IgE-reactivity (40).
  • Reactivity on ELISA immunoblots was found in 23% of 26 mugwort-allergic European patients’ sera (41).
  • Homologous to Amb a 9 (ragweed) and Bet v 4 (birch) with a sequence identity of 82% (40) and 68% respectively (32).
Art v 6 Pectate lyase 42
  • Minor allergen (37).
  • Reactivity on ELISA immunoblots was found in 26% of 26 mugwort-allergic European patients’ sera (41).
  • Sequence identity with Amb a 1 (ragweed) was found to be 65% (32).

kDa: kilodaltons, IgE: Immunoglobulin E, ELISA: Enzyme-linked immunosorbent assay

Another 60 kDa acidic glycoprotein allergen is reported but is not listed in IUIS allergen nomenclature. The sensitization prevalence of this Art v 60kDa allergen was found approximately 70% in mugwort-allergic patients (32).

Biomarkers of severity

Specific IgE activity to Art v 1 is indicative of sensitization to mugwort, especially in China(21). Art v 3 serves as a molecular biomarker for diagnosing pollen-related allergy to food in patients with season-specific pollen allergies (22).

Cross-reactivity

Mugwort exhibits widespread cross-reactivity with other Asteraceae (Compositae) family members (ragweed, sunflower seeds, other Artemisia species) due to the presence of pan-allergens like profilin (Art v 4) and calcium-binding proteins (Art v 5) in addition to defensin protein (Art v 1)(5, 7, 12). Mugwort and ragweed (Ambrosia artemisiifolia) are highly cross-reactive due to the presence of common allergenic structures on their pollens This cross-reactivity may be attributed to profilin and calcium-binding allergens (5). Art v 1 (defensin), Art v 6 (pectate lyase) and Art v 4 (profilin) show considerable cross-reactivity with their homologous proteins in ragweed i.e., Amb a 4, Amb a 1 and Amb a 8 respectively (34, 37, 42).

Furthermore, cross-reactive non-specific LTPs, profilins, carbohydrate determinants, and high molecular weight allergens of mugwort may be responsible for the numerous mugwort-food allergy connotations (6). Various allergens were identified for PFAS like celery-mugwort-spice (Art v 4 with Api g 4 of celery and Dau c 4 of carrot), mugwort-fennel (Art v 60kDa with Foe v 5 of fennel), mugwort-mustard (Art v 3 with Sin a 3 of mustard, Art v 4 with Sin a 4 of mustard) and mugwort-peach (Art v 3 with Pru p 3 and Art v 4 with Pru p 4) (34).

The mugwort-pollen profilin (Art v 4) was also found cross-reactive with lychee (Litchi chinensis) profilin (Lit c 1). Mugwort-chamomile cross-reactivity was also reported and possible cross-reactive allergen identified was Art v 1 (34) Moreover, sunflower allergy in patients sensitized to mugwort is caused by cross-reactivity between defensin molecules, Art v 1 with Hel a 4 in addition to LTP, Art v 3 with Hel a 3 (12, 34).

Compiled By

Author: Turacoz Healthcare Solutions

Reviewer: Dr. Fabio Iachetti

 

Last reviewed: December 2020

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