Typ:
Whole Allergen
Allergengesamtextrakt
Whole Allergen
Mustard
Ingestion
Brassicaceae
Sinapis alba or Brassica juncea or Brassica nigra
Brassica/Sinapis spp.
Yellow/white mustard, brown mustard, black mustard, red mustard, Chinese mustard, Indian mustard, Asiatic mustard, oriental mustard, leaf mustard, sarepta mustard, wild mustard, gai-choi
Mustard is the most important spice crop available globally, that belongs to the family Brassicaceae. Mainly, three species of this family are used in food industry: white (Sinapsis alba), brown (Brassica juncea) or black (Brassica nigra) mustard. Mustard is widely used in Indian, French, German and Irish cuisines, as well as for medicinal purposes. This plant is native to Asia, especially China, but has now spread throughout Asia, Japan, Africa and Europe. The prevalence of mustard allergy is common in Europe, where the consumption is comparatively higher, particularly in France.
Oral ingestion of mustard can lead to allergic reactions, such as oral allergy syndrome and anaphylaxis, allergic rhinitis, asthma and atopic dermatitis. Four of the proteins from white mustard, named, Sin a 1, Sin a 2, Sin a 3 and Sin a 4, and only one protein from brown mustard, Bra j 1, have been identified as having allergenic potential.
Cross reactivity between mustard and mugwort pollens is widely reported as the mugwort-mustard allergy. Besides mugwort, it also shows cross reactivity with nuts, legumes, corn, peach (Rosaceae fruits), cabbage, cauliflower and broccoli (Brassicaceae vegetables).
Globally, mustard plant is considered as the most essential spice crop available, which belongs to the genus Sinapis and Brassica of the Brassicaceae family (1). This family includes a number of other plants, such as turnip, rape, cabbage, etc. (2). It is an annual, perennial or biennial, woody cultivated herb, generally 1-3 m tall. The mustard leaves are alternate, petiolate, non-stipulated with reticulate venation. It has branched taproots with erect, cylindrical, and smooth branched stem. The plant possesses bright yellow hermaphrodite flowers, with the stalk of the four flowers having a cross-like arrangement. The fruits of the mustard plant have narrow siliqua with tiny, globose and exalbuminous seeds. The plant is considered mature when the seedpods become yellow, dark and rattle in the pods while being shaken (1).
Mustard has got its own historical and cultural importance, besides its use in several cuisines. It is considered as one of the oldest spices available, as it has been described in Ancient Sumerian, Sanskrit, Egyptian and Chinese texts or writings since thousands of years. It has also been used by the Greeks and Romans for medicinal purposes. The current English name “mustard” has been derived from Latin “mustum-ardens”, meaning “burning-must” (must: mixing of seed powder with unfermented grape juice and ardens: to burn).
Mustards are particularly popular for their unique characteristics, like pungent and hot taste. Mustard powder can be mixed with vinegar or other seasonings to prepare several condiments. Also, white, black and brown mustards are mixed in certain blends to create specific aromas or flavors (1). Presently, mustard is used in Indian, German, French and Irish cuisines. The mustard leaves and seeds are widely used in large varieties of food items and are sometimes also present as a hidden ingredient in many foods, such as sauces, salad dressings, salad greens and processed foods (3, 4). Besides food, it also has medicinal, pharmaceutical, and industrial applications (5).
Mustard is usually a cool climate crop and it is well-cultivated in tropical and temperate zones (1, 6), with temperatures ranging from 5-27℃ (1, 6). The most suitable soil pH for it is neutral pH 7 (1, 6), however, it can also grow in the pH between 4.2 and 8.3 (1). A wide range of soil conditions, varying from sandy loam to clay loam is suitable for mustard growth, although it grows best on light sandy loam soils, that are well-aerated with limited rainfall (1, 6). The annual rainfall required for the growth of mustard is between 0.3 to 4.2 m (1, 6).
Three species of mustard belonging to the family Brassicaceae are widely used in the food industry (4, 7):
1. White or yellow mustard (Brassica alba [synonyms: S. alba, B. hirta]).
2. Black mustard (B. nigra [synonym: S. nigra, B. sinapioides]) – A Eurasian variety and an important oil source.
3. Brown mustard (B. juncea [synonym: B. integrifolia]) – Also named as oriental mustard, Indian mustard, Asiatic mustard, Chinese mustard, leaf mustard and Sarepta mustard. This species is used as a common spice, herbal food, and as a source of oil.
Sinapis and Brassica are closely related genus with some identifiable differences. The plants of Sinapis genera have light green leaves with clawed fruits, while the plants of Brassica genera have greyish-green leaves with smooth-surfaced fruits (1).
Taxonomic tree of Mustard tree (3,8) | ||||
---|---|---|---|---|
Domain | Eukaryota | |||
Kingdom | Plantae | |||
Phylum | Spermatophyta | |||
Subphylum | Angiospermae | |||
Class | Dicotyledonae | |||
Order | Capparidales | |||
Family | Brassicaceae | |||
Genus | Sinapis | Brassica | Brassica | |
Species | Sinapis alba | Brassica juncea | Brassica nigra |
Ingestion of mustard seeds in various forms in food can lead to immunoglobulin E (IgE)-mediated allergic reactions (4). Mustard seed allergens Sin a 1 and Sin a 3 are regarded as true food allergens that are capable of inducing primary sensitization and provoking severe allergic reactions (9).
The prevalence rates of mustard allergy appear to vary worldwide due to different eating habits. It is commonly found in Europe, where the consumption is comparatively higher than the rest of the world, particularly in France, accounting for 1-7% of food allergy being estimated through various studies (10). It is considered the fourth most common food allergen in France (4).
In a prospective study conducted in France on 544 hypersensitive children, 9% reported mustard food allergy (11). In another French prospective study conducted on 30 subjects sensitized to mustard, allergic reactions were reported in 23.3% of subjects in double-blind or single-blind oral food challenge (2). Mustard was the cause of food allergy in 4% of children with atopic dermatitis, based on a study conducted in France (12).
Mustard is also increasingly being used in Spanish cuisine, however, only a few case reports of contact dermatitis, urticaria, and anaphylaxis have been reported. No extensive prevalence studies have been published so far (4, 13). In a study conducted on 49 patients mono-sensitized to lipid-transfer proteins (LTP) in Italy, 4% of patients were found to be sensitive to mustard (14).
Furthermore, mustard is also widely used in India, however, limited data is available regarding its allergy. In a prospective study conducted in India on 78 allergic rhinitis patients, mustard showed positive SPT in 78.2% of the patients (15). Another study conducted in India reported 11 food-allergic patients showing elevated specific IgE to mustard (n=138) (16).
Although the prevalence of mustard allergy in Canada is less known, its severity is reported to be high, with reports of serious reactions like anaphylaxis, after consuming a small quantity of mustard (17).
Allergy to mugwort could pose a risk of mustard allergy, due to the high prevalence of mugwort-mustard allergy syndrome. Also, patients allergic to mustard should avoid all the other members of the Brassicaceae family (18).
According to a prospective study performed on 35 children with positive SPT to mustard, allergy to mustard was found to begin early in life, however, its clinical symptoms in children were not as severe as in adults. The most common clinical symptom found was atopic dermatitis, while severe allergic reactions like anaphylaxis were not seen in children (18).
Mustard plant is native to China and other parts of Asia. Its use has become prominent as a common spice and has spread throughout Asia, Africa and Europe. The three varieties of mustard (white, brown and black) have become an important spice crop for commercial cultivation, and the largest exporters for these crops are Canada, India, Austria, Holland, England, Germany, France, Italy, Western United States and Northern Africa (1). Canada is considered as the second-largest producer of mustard seed worldwide, and the first largest exporter, with around 57% of the global market share (5).
Black mustard is commonly used as table mustard. Brown mustard, also known as Indian or oriental mustard, is used for mustard greens and seeds in various preparation as well as for cooking oils in Asia. White mustard display hairy seedpods and are commonly used in America (yellow mustard) as table mustard and as greens in salad (1).
Mustard is considered a priority food allergen and it is regulated by countries such as Canada, the Gulf Cooperation Council (Saudi Arabia, United Arab Emirates, Kuwait, Bahrain, Oman, Qatar and Yemen), and the European Union (5).
Oral ingestion of mustard through food items is the primary route of exposure to allergy (4,19).
Inhalation could be the secondary route of allergen exposure. This was demonstrated by a study conducted on 35 atopic hypersensitive patients to mustard, where respiratory tract symptoms were found to precede onset of food allergy in 29 patients, indicating primary sensitization through inhalant or respiratory route (18).
Oral allergy syndrome (47.4%) was found to be the most frequent symptom in a prospective study conducted on 38 mustard-hypersensitive patients, followed by urticaria or angioedema in 42.1% and systemic anaphylaxis in 10.5%, with one incidence of mustard-dependent exercise-induced anaphylaxis (18).
Severe skin reactions such as urticaria and angioedema have also been reported due to the ingestion of mustard, in forms like sauce or dips. Furthermore, it is considered as one of the most common spices that causes IgE-induced severe anaphylaxis (19). Certain case reports exist, showing mustard-induced skin allergies, that may manifest as contact dermatitis, eczema, pruritic lesions, urticaria or angioedema. This may be due to the presence of a volatile agent in mustard oil, known as allyl isothiocyanate, responsible for the particular pungent odor (4).
The clinical manifestations of mustard allergy, observed in a study conducted on 49 mustard-allergic children in France, included skin reactions (urticaria, angioedema) in 21 patients (42.8%), gastrointestinal reactions in 1 patient (2%) and conjunctivitis in 2 patients (4%). The oral allergy syndrome and anaphylaxis were also reported in 2% of children (11). In another prospective study conducted on 29 mustard-allergic patients in Spain, skin reactions like angioedema and general urticaria were reported in 55.2% and 34.5% patients, respectively. Furthermore, 17.2% of patients reported gastric symptoms, 27.6% reported oral allergy syndrome, 37.9% reported respiratory symptoms, like dyspnea, 13.8% reported conjunctivitis and 48% of patients reported anaphylaxis (13).
Mustard-induced anaphylaxis has been reported for the last 20 years. Several cases have been identified in France, Spain, Germany and the USA, where anaphylactic reactions to mustard have been reported after ingestion of food-containing mustard (4, 20). In a study conducted in France, mustard was the cause of anaphylactic reactions in 3% of patients with severe reactions to food (n=60) (21).
In a prospective study conducted on 29 mustard-allergic individuals in Spain, allergic rhinitis was reported in 10.3% of patients (13). In another prospective study involving 35 atopic patients with mustard hypersensitivity in Spain, allergic rhinitis was reported in 33 patients (94.2% ) (18).
In a prospective study conducted in France, the prevalence of asthma was reported to be 4% in mustard-allergic children (2 out of 49 children) (11). In another prospective study involving 35 atopic mustard-hypersensitive patients in Spain, 22 patients reported bronchial asthma (62.8%) (18).
Atopic dermatitis was found to be commonly reported in patients with mustard allergy. In a prospective study conducted in France, the prevalence of atopic dermatitis was reported to be 42.8% in mustard-allergic children (21 out of 49 children) (11). In a prospective study involving 35 atopic mustard-hypersensitive patients in Spain, atopic dermatitis as well as respiratory symptoms were observed in 4 patients (11.4%) (18).
Two case studies (case 1: female aged 48 years and case 2: male aged 25 years) with allergic contact dermatitis were identified (India and China), with reports of positive patch test to mustard (19).
The World Health Organization (WHO) and International Union of Immunological Societies’ Allergen Nomenclature Subcommittee (IUIS) have registered four allergenic components, i.e., Sin a 1 (2S albumin), Sin a 2 (11S globulin), Sin a 3 (LTP) and Sin a 4 (Profilin) for white/yellow mustard (S. alba), while only one allergen has been identified from brown/Indian/oriental mustard (B. juncea): Bra j 1 (2S albumin) (4, 22).
Allergen | Isoallergen | Biochemical name | Molecular weight (kDa) | Allergenicity |
---|---|---|---|---|
Sinapis alba (White/Yellow mustard) | ||||
Sin a 1 | Sin a 1.0101 | 2S albumin | 14 | Major and most prevalent allergen. 100% of mustard-sensitive patients showed IgE binding to Sin a 1 on immunoblot (n=11) (4, 22). 78.1% patients tested positive for SPT (n=32), while 73.5% patient’s sera showed positive IgE on ELISA (n=34) (23). |
Sin a 2 | Sin a 2.0101 | 11S legumin like protein | 51 | Major allergen. 44% of mustard-allergic patients were reported positive in ELISA (n=39) (4, 22). 59.3% patients tested positive for SPT (n=32), while 47% patient’s sera showed positive IgE on ELISA (n=34) (23). |
Sin a 3 | Sin a 3.0101 | Non-specific LTP type I | 12.3 | Minor allergen. 41.1% of patient’s sera had positive IgE to recombinant (r) Sin a 3 on ELISA (n=34) (23). |
Sin a 4 | Sin a 4.0101 | Profilin | 13-14 | Minor allergen. 23.5% of patient’s sera had positive IgE to recombinant (r) Sin a 4 on ELISA (n=34) (23). |
Brassica juncea (Indian or oriental mustard) | ||||
Bra j 1 | Bra j 1.0101 | 2S albumin seed storage protein | 14 | Closely related to Sin a 1. 64% mustard-sensitive patients showed IgE binding to synthetic peptide of large chain of Bra j 1 (n=11) (4, 22). |
kDa: kilodaltons, IgE: Immunoglobulin E, SPT: Skin prick test; LTP: Lipid transfer protein; ELISA: Enzyme-linked immunosorbent assay.
From S. alba variety, eight isoforms of Sin a 1 have been identified via deoxyribonucleic acid cloning and sequencing techniques (Sin a 1.0101, Sin a 1.0102, Sin a 1.0103, Sin a 1.0104. Sin a 1.0105, Sin a 1.0106, Sin a 1.0107 and Sin a 1.0108) (24), while from the B. juncea variety, a new IgE-binding mustard protein has been identified, as oleosin (oil-body protein) and enolase enzyme. However, biological and structural characterization of this newly recognized allergen is still pending (5).
In a study conducted on 34 mustard allergic patients, Sin a 1 allergen was recognized as a true potential marker of sensitization to mustard, while Sin a 2 was found to be associated with severe symptoms, after ingestion of mustard (4, 23).
It has been shown that steps such as thermal processing/enzymatic digestion are not enough for suppressing the allergenicity of mustard seed allergens. However, extrusion process (preconditioning [35℃] and flaking, steam heating [80-125℃ for 15-20 min], mechanical pressing, solvent extraction and finally de-solventising [103-107℃]) can suppress the allergenicity by the way of removing the potential allergens from mustard oil (4, 25).
Cross-reactivity between aeroallergens, like pollens and mustard, is widely reported (18). Association between mustard and mugwort (Artemisia vulgaris) pollen was found to be significant (p<0.001) in studies conducted on patients with mustard hypersensitivity (13, 18).
The mugwort-mustard allergy is a term coined to describe this association of mugwort pollinosis, with food allergy from the Brassicaceae family members like white and Indian mustard, and others such as cabbage, broccoli and cauliflower. The cross-reactive allergen components, responsible, are not yet confirmed, but possible ones include LTPs (Art v 3, Sin a 3), profilins (Art v 4, Sin a 4) and Art v 60 kDa (26, 27).
Mustard as a hidden allergen is found to have potential cross-reactivity with allergens of nuts, legumes, corn and Rosaceae fruits, especially peach (4, 28, 29). In a prospective study conducted on 38 Spanish mustard-allergic patients, all were found sensitized to other members of the Brassicaceae family (cabbage, cauliflower and broccoli), while 97.4% were sensitized to nuts (excluding almond and peanut), 94.7% to legumes, 78.9% to corn and 89.5% to Rosaceae fruits, suggesting cross-reactivity among them (4, 18). Additionally, cross-sensitization was observed to be significant (Pearson correlation=0.006) among mustard and peach, in an observational cohort study involving 35 peach-allergic patients (30).
A review suggested that no clinical cross-reactivity at either inhalation or food allergy level exists between rapeseed and mustard, although cross-sensitization may be present (28). However, Sin a 1 showed marked cross-reactivity with rapeseed allergen Bn III at IgE antibody level. Furthermore, 2S albumin from sunflower seed was found to be cross-reactive with 2S albumin of mustard (4).
Sensitization to foods from the Rosaceae family and pollens may be attributed to Sin a 3 and Sin a 4 (23). A study revealed that 11S globulins from tree nuts, such as pistachio, almond, hazelnut and walnut shared IgG epitopes with Sin a 2 and reduced its IgE binding ability. A similar effect was not observed with peanut (31). Further, no cross-reactivity was observed between Sin a 1 and proteins of the Brassicaceae family, with similar genetic homology (28).
Sequence similarity of mustard LTP Sin a 3 is reported to be 65% with LTP from cabbage (Bra o 3) and 50-55% with LTP from peach (Pru p 3), apple (Mal d 3), cherry (Pru a v 3) and hazelnut (Cor a 8), as well as with pathogenesis-related PR-10 protein (Fra a 3). Moreover, the sequence similarity of mustard profilin Sin a 4 has been shown to be around 80% with profilin from melon (Cuc m 2) and peach (Pru p 4), and also some similarity with profilins from chenopod (Che a 2) and birch (Bet v 2) (4).
Author: Turacoz Healthcare Solutions
Reviewer: Dr. Fabio Iachetti
Last reviewed: December 2020