Common allergens in Hong Kong
General concept
Most allergens are small proteins or glycoproteins (5-100 kDa). For an aeroallergen to be clinically significant, it must be buoyant in the air, be present in significant amount, and be able to induce an IgE-mediated response. Small allergen particle will be carried by the wind and to be deposited within the respiratory mucosa and conjunctiva. Large particles, in comparison, settle more quickly except in high winds. Size of various allergen types are as follows:
Allergen | Size in diameter |
Tree, grass and weed pollens | 20–60 μm |
Fungal spores | 3–30 μm |
Mite particles | 1–10 μm |
The upper airway filters the larger allergens, with particles smaller than 7 μm depositing in the airways and those smaller than 3 μm settle on the distal alveoli. The conjunctivae and upper airways receive the largest amount of airborne allergens.
In addition to size, allergenicity is also influenced by
- How the allergen is broken down
- How fast that various allergens are released
- The biochemical function of the allergens
- The intrinsic allergenicity of the protein
- Enzymatic properties of allergens, such as dust mite proteases, may facilitate an allergic response
Each aeroallergen may contain one or more allergenic proteins that can initiate an allergic response. Proteins that bind to ≥ 50% of the IgE-enriched sera from sensitized patients are called major allergens. The proteins that bind to < 50% are termed minor allergens. The allergen was described based on the first three letters of the genus and the first letter of the species (in italics) and then by a Roman numeral to indicate the allergen in the chronological order of purification. For example, a major allergen from house dust mite Dermatophagoides pteronyssinus is designated Der p1.
Remarkably, only a small number of proteins of the plant and animal proteome are known as allergens. Therefore, allergens have been clustered according to their common structural, biochemical and functional features to less than 2% of all known protein families. These clusters allow evaluating the risk of cross-reactivity.
Other factors that determine the allergenicity of proteins include:
- the amount and duration of exposure to the immune system
- environmental conditions including microbial exposure
- immune-modulating components of allergenic sources facilitating Th2 immune responses
- the intrinsic effects of proteins on the innate and adaptive immune system.
Common allergens relevant in Hong Kong
Dust mites (D. pteronyssinus, D. farinae, Blomia tropicalis)
There are many substances in household dust which can cause allergies in humans, including animal dander, insect parts (especially from cockroaches), mold spores and pollen. The most common allergenic components of house dust, however, are from dust mites.
Common dust mites belong to the family Polyglyphidae of the order Acarina, which itself belongs to the class Arachnidae. The main family of mites associated with human atopic diseases is Pyroglyphidae, Thirteen species of Pyroglyphidae are contained in house dust, where they co-habit with storage mites of other families, i.e. Acaridae and Glycyphagidae.
Dust mites are generally tiny globular creatures related to ticks, chiggers, and spiders, with clear to creamy white color and with hairy legs and body. Their size is about 0.5 mm long and are visible only with the aid of a microscope. Food sources of mites include skin scales or fungi that grow on them. Growth of Pyroglyphidae is limited by predation by other mites, and excessive fungal growth inhibits growth of cultured mites.
There are two common species of dust mite in Hong Kong, the North American house dust mite, Dermatophagoides farinae, and the European house dust mite, Dermatophagoides pteronyssinus. Their genera name contains a clue to these mites‘ favorite food: in Greek derma = skin and phagein = eat.
Table below shows biological characteristics of the two house dust mites
Dermatophagoides pteronyssinus | Dermatophagoides farinae |
It has a worldwide distribution but is more abundant in Europe than in America. It prefers more humid climates than D. farinae does. The duration of the life cycle from egg to adult is 31 days and the female lives approximately 70 days, but these periods depend on the temperature and humidity of the environment. It lays about 80 -120 eggs over a 45-day period. | It is also found worldwide but is more abundant in North America than in Europe. It seems to prefer more continental and barren climates than D. pteronyssinus does. The duration of the life cycle from egg to adult is 35 days, and the female also lives approximately 70 days. D. farinae lays eggs over a 30- day period, producing about an egg a day. |
House dust mites live in bedding, upholstered furniture, and carpets, thrive in summer and die in winter. The optimum living conditions are temperatures of 25 – 30°C and a relative humidity of 65 – 80%. They therefore reproduce faster in summer, but continue to thrive even in the coldest months. Dust provides a detrital habitat with 3 key macromolecules derived from organic debris: keratin (human skin scales), cellulose (textile fibers), and chitin (fungal hyphae and mite cuticles). The availability of these substances affects the success of the mite, with keratin, the primary food source, being most important. However, the HDM diet also extends to fibers, bacteria, pollen, fungal mycelia, and the spores of micro- organisms. During digestion, disassociated digestive cells from the gut wall bind to ingested food en route through the lumen. These cells contain allergenic digestive enzymes that are excreted in the fecal pellets.
Another dust mite common in Hong Kong is Blomia tropicalis (Bt). It is a notable mite species in many parts of the world, and the most common and most important mite species in tropical countries like Singapore or Hainan Island and Chongqing city in mainland China. While the allergens from Dp and Df cross react extensively, Bt represents another type of mite which has very minimal cross reactivity to the Dp and Df. Therefore, in order to have precise clinical diagnosis and hence effective causative treatment with allergen immunotherapy, patients in Hong Kong should be tested for the three mites with SPT, ALFA or serum specific IgE test.
Mite allergens are present in mite bodies, secrete, and excreta; fecal particles contain the greatest proportion of mite allergens. They can be detected in many areas of the home, including beds, carpets, upholstered furniture, and clothing, leather-covered couches and wood furniture. Beds are the ideal habitat for mites, since they provide the ideal temperature, food, and moisture for their proliferation. The allergens they produce may accumulate deep inside mattresses, pillows, and carpets, especially when they are old.
It was found that a concentration threshold of 2μg Der p 1 per gram of dust increased the risk of sensitization (which corresponds approximately to 100 mites/g of dust) and BHR (J Allergy Clin Immunol 1989; 83: 416–427), whereas, exposure to 10μg Der p 1 per gram of dust is associated with an increased risk of exacerbations of asthma. However, it must be emphasized that these are just statistical thresholds. Personal exposure to HDM allergens is combined with other risk factors for asthma development.
Important components of mite allergens
Species | Allergen | Biochemical | Category |
D. pteronyssinus | Der p1 | Cycteine protease | Major |
Der p2 | ML Lipid binding | Major | |
Der p23 | Peritrophin | Major | |
Der p4 | Amylase | Mid tier | |
Der p5 | Unknown | Mid tier | |
Der p7 | LPS/BPI family | Mid tier | |
Der p21 | Der p5 – related | Mid tier | |
D. farina | Der f1 | Cysteine protease | Major |
Der f2 | ML Lipid binding | Major | |
Other | Not investigated | No investigated | |
B. tropicalis | Blo t5 | Unknown | Major |
Blo t21 | Blo t5 – related | Major | |
Blo t7 | LPS/BPI family | Mid tier | |
- Mites allergens which have IgE-binding titres expected to make significant contributions to the total anti-house dust mite titres.
- LPS/BPI: lipopolysaccharide binding/bacterial permeability increasing protein
Avoidance measure of dust mites:
According to recommendation by WAO (World Allergy Organization), there are three main measures that need and can be taken to avoid house dust mites:
- Reduce accumulation of dust in general
- Separate the patient from the dust
- Decrease mites and/or their secretions
In practice, the following priority measures and long-term modifications should be made:
Priority Avoidance Measures:
- Encase mattress and all pillows in allergen-proof covers. It is recommended to use those made of vinyl or 6μm micro denier, or covers which are fabric backed with vinyl or urethane membrane.
- Wash bed linens weekly in hot water, at least 55°C (130°F), and damp wipe mattress covers weekly.
- Encase box spring in vinyl or plastic covers.
- Reduce clutter/toys/other collections throughout the house, but especially in the bedroom.
- Minimize visits to friends and relatives with feathered or furry pets.
- Vacuum or dust weekly. Make sure to wear a mask and leave area for 20 minutes after cleaning.
- Use a vacuum cleaner that incorporates a double-thickness bag and HEPA filter leak little allergen.
- Place stuffed animals in freezer overnight at least once a week, or wash in hot water weekly. Either method will kill the dust mites which may have infested the child’s toys.
- Hang comforters or bedspreads outside in dry, wintery weather.
- Clean or replace heat/air conditioner filter as per manufacturer’s instructions.
Long-term Modifications:
- Reduce indoor relative humidity (RH) with air conditioning or the use of a dehumidifier. 30%-45%RH is considered optimal.
- Humidity can also be controlled by increasing ventilation if outdoor conditions are cold and/or dry.
- Replace carpet with solid surface flooring, like wood, vinyl, linoleum or tile.
- Replace upholstered furniture with leather, vinyl, wood or plastic.
- Replace drapery with shades or blinds which are easier to maintain or with washable curtains.
Cockroach
Cockroach allergy is especially important for the development of asthma in inner cities among lower socioeconomic groups. Certain proteins in cockroach feces and saliva can be found in house dust. They can trigger mild-to-moderate symptoms include sneezing and rhinorrhea, skin reactions (mild dermatitis), and eye irritation, with difficulty in breathing and possible anaphylactic episodes occurring in more severely allergic individuals.
All cockroach species are adept crawlers. Species differ in capacity of flight, morphology (size, color), response to light, geographic location, and domestic habitat. The two most common species associated with allergic disease in Hong Kong are the American (Periplaneta americana), which is 34–53 mm long, reddish brown, and capable of flight and German (Blattella germanica) cockroaches, which is 16mm long, brown, nocturnal, incapable of flight, and strictly domestic.
Cockroach allergy can result from initial sensitization to allergens mostly through inhalation, but also by ingestion or transdermal exposure due to abrasion or injection. Potential sources of relevant cockroach allergens in the environment include whole bodies, cast skins, secretions, egg casings, and/or fecal material. It was found that patient exposed to 8 U/g of dust for either Bla g 1 or Bla g 2, equivalent to 80 and 320 ng/g for Bla g 2, would increase the risk of asthma (J Allergy Clin Immunol 2001; 107: 48–54; Thorax 1999; 54: 675–680). In US, 10% of living rooms were above this point (Environ Health Perspect 2006; 114: 522–526).
Airborne cockroach allergens are associated primarily with amorphous and larger particles (10 μm) (which settle after disturbance) than are particles from animals like cats and dogs. Early clinical studies provided evidence that cross-reactivity occurs among homologous allergens from American, German, Madagascar, Asian, and Oriental cockroaches (Clin Allergy Immunol 2008; 21: 183–200.) There is also extra-species cross reactivity (“pan allergy”) with a number of other arthropods such as crustaceans (shrimp, crab, and lobster), insects (silver fish), arachnids (dust mites) and mollusks (oysters, mussels, scallops, clams). Since both exposure and allergy to cockroach are not uncommon in Hong Kong, patients with asthma or rhinitis should be routinely evaluated for this type of allergy.
Major and relevant minor Cockroach Allergens
Allergenic molecule | Biochemical name | Prevalence of allergen-specific IgE among pt. (%) |
Blattella germanica | ||
Bla g 1 | Midgut microvilli protein-homolog | 20-50 |
Bla g 2 | Unusual aspartic protease | 40-70 |
Bla g3 | Arylphorin/hemocyanin | |
Bla g 4 | Lipocalin | 17-60 |
Bla g5 | Glutathione S-transferase | 35-73 |
Bla g 6 | Troponin C | 14 |
Bla g 7 | Tropomyosin | 18 |
Bla g 8 | Myosin light chain | 14 |
Bla g 11 | Alpha-amylase | |
Periplaneta americana | ||
Per a 1 | Midgut microvilli protein-homolog | 30-50, 100 |
Per a 2 | Aspartic protease-like | |
Per a 3 | Arylphorin/hemocyanin | 26-95 |
Per a 6 | Troponin C | 17 |
Per a 7 | Tropomyosin | 13-54 |
Per a 9 | Arginine kinase | 80-100 |
Per a 10 | Serine protease | 80 |
Cockroach Control Measures
- Physical Measures
- Reduce access to food
- Store food in sealed containers
- Eliminate sources of organic debris
- Reduce access to water
- Repair leaking faucets
- Wrap pipes to prevent condensation
- Eliminate damp areas beneath sinks
- Repair damp, damaged wood
- Improve ventilation by eliminating clutter beneath sinks
- Eliminate hiding places and access points
- Caulk and seal cracks and crevices in foundations
- Caulk around water pipes’ entry into house and beneath sinks
- Eliminate clutter within household (e.g., remove all newspaper and magazine storage areas)
- Reduce access to food
- Chemical Measures
- Aerosol sprays of organophosphates like chlorpyrifos
- Pyrethrum or pyrethroids
- Boric acid powders and baits
- Orange guard (D-limonene)
- Bait stations
- Hydramethylnon (Combat®)
- Abamectin (Roach Ender®)
- Fipronil (Maxforce® Roach Bait Station)
- Roach FreeTM System (food source with boric acid)
- Aerosol sprays of organophosphates like chlorpyrifos
Baits with other active ingredients (sulfluramid, xanthins, oxypurinol)
Household pets
Household pets are the most common source of allergic reactions to animals. Many people think that pet allergy is provoked by the fur of cats and dogs. Researchers have found, however, that the major allergens are proteins in the saliva. These proteins stick to the fur when the animal licks itself. Urine is also a source of allergy-causing proteins, as is the skin. When the substance carrying the proteins dries, the proteins can then float into the air. Cats may be more likely than dogs to cause allergic reactions because they lick themselves more, may be held more, and they spend more time in the house, close to humans.
Allergies to animals can take two years or more to develop and may not decrease until six months or more after ending contact with the animal. Carpet and furniture are a reservoir for pet allergens, and the allergens can remain in them for 4 to 6 weeks. In addition, these allergens can stay in household air for months after the animal has been removed. Therefore, it is recommended that people with an animal allergy should check with the landlord or previous owner to find out if furry pets lived on the premises.
Cat allergen
Exposure to cat allergens in schools may lead to asthma exacerbations in cat-sensitized students. In classrooms with a high number of cat-owners, allergen levels measured are considered to be high enough to induce sensitization to cat (Allergy 2002;57:357-361).
Cat produces 7–8 different proteins. However, there is only one major allergen, Fel d 1. It is the only cat allergen which can induce specific IgE production in a high percentage of cat-sensitized patients (about 85–95%) (Clin Allergy 1976;6:419–428). It is also responsible for 80%–90% of the IgE-binding capacity of cat allergen extracts. (J Allerg Clin Immunol 1999; 104: 1223–30). The removal of Fel d 1 from a dander extract decreases the histamine releasing capacity of the preparation 200- to 300-fold. The physiological function of Fel d 1 is unknown. Some studies suggest that this protein may play a role in the protection of epithelia, in pheromonal regulation or in inter-cat communication.
Fel d 1 is found in hair roots and sebaceous glands, in dander, saliva, and lacrimal fluid, and in high concentrations in anal glands. A single cat is able to produce 3–7 μg/day. The quantitatively most important sources of the allergen are the sebaceous, salivary and perianal glands, whereas the skin and the fur are the principal reservoirs. Since Fel d 1 production is under testosterone control, males produce higher quantities than female. Fel d 1 is a heat stable protein. Expose it at 140°C for 60 min results in only 30% denaturation of the molecule.
It has also been demonstrated that cat albumin may determine IgE responses in about 20% of subjects sensitized to cat, but only a few patients are sensitive only to this allergen. Recently, a new allergen was identified; it is called cystatin (Fel d 3) and is a member of the cysteine protease inhibitory family. Fel d 3 is able to induce IgE responses in about 10% of patients with cat allergy (Int Arch Allergy Immunol 2001;124:55–56).
An important characteristic of cat dander particles is that these can ‘stick’ to all available surfaces such as walls, furniture and clothing, with consequent distribution of cat allergens in indoor environments which should be theoretically ‘cat free’ (houses, schools, means of transport and different public buildings). This indirect exposure to cat allergens in cat-free environments may also be of sufficient magnitude to cause airway sensitization and/or triggering of asthma exacerbation in already sensitized patients (J Allergy Clin Immunol 1993;91: 1067–1074).
Several recent studies have suggested that early exposure of children to allergens derived from domestic animals (especially cats) might induce a lower degree of allergic sensitization to these proteins. These results have been confirmed also among pre-teenage children (Am J
Respir Crit Care Med 2002;166:696–702). Other studies have shown that children raised in a house with 2 or more dogs or cats in the first year of life have not only less allergic sensitization to the allergens of these animals but also less sensitization to other common allergens (JAMA 2002;288:963–972). Platts-Mills et al. demonstrated that a high level of exposure to cat allergens in children is associated with a lower risk of sensitization to cats (Lancet 2001;357:752–756.). This is in contrast to mites that increasing exposure to mites was associated with increased prevalence of sensitization to mite allergens.
Measure to minimize exposure to cat allergens
Removal of cat(s) from the house
- After removal, it is necessary to vacuum clean and wash all surfaces (including walls) on which Fel d 1 may have accumulated
- Carpets and upholstery must be cleaned and bedding must be
- washed
If patients choose to keep the cat at home
- Use a vacuum cleaner equipped with a HEPA filter1 and double thickness bags in order to remove pet allergens from reservoirs
- Remove carpeting from all environments and replace with linoleum or wood flooring
- Wash bedding in water weekly
- Cats should be washed twice weekly to obtain a significant reduction of Fel d 1 shedding
- Cat beds must also be washed
- Cat must be kept outdoors as much as possible and must not enter bedrooms and living rooms
- The indoor environment must be naturally ventilated
- Washing (water or dry cleaning) the clothes of cat owners and avoiding the use of allergen-contaminated clothes outdoors prevent the dispersal of Fel d 1
Dog allergen
Dog allergy is a public health burden, highly associated with both asthma and allergic rhinitis. Dog allergens are present in dog hair/ dander extract. It has been shown that the origin of dog allergens is not the skin, but the saliva. Dog allergen proteins stick to the hair/skin when grooming and then spread into the house dust via dog hair and dander.
Characteristics of various dog allergens
Allergen | Biochemical name | MW (kDa) | Primary site to find | % of patient sensitized | Reference |
Can f 1 | lipocalin | 23-25 | Saliva/danders | 50 – 70% | 1, 2, 3, 4 |
Can f 2 | lipocalin | 19 | Saliva/danders | 25 – 40% | 2, 3, 4 |
Can f 3 | serum albumin | 69 | Saliva | 35% | 5 |
Can f 4 | lipocalin | 18 | Saliva/danders | 35 – 60% | 3, 6 |
Can f 5 | kallikrein | 28 | Urine | 70% | 7 |
Can f 6 | lipocalin | 27-29 | Danders | 38 – 61% | 8, 9 |
- Schou C, Svendsen U, Løwenstein H. Purification and characterization of the major dog allergen, Can f I. Clin Exp Allergy 1991; 21: 321–8.
- Konieczny A, Morgenstern JP, Bizinkauskas CB, et al. The major dog allergens, Can f 1 and Can f 2, are salivary lipocalin proteins: cloning and immunological characterization of the recombinant forms. Immunology 1997; 92: 577–86.
- Saarelainen S, Taivainen A, Rytkönen-Nissinen M, et al. Assessment of recombinant dog allergens Can f 1 and Can f 2 for the diagnosis of dog allergy. Clin Exp Allergy 2004; 34: 1576–82.
- Madhurantakam C, Nilsson O, Uchtenhagen H, et al. Crystal structure of the dog lipocalin allergen Can f 2: implications for cross-reactivity to the cat allergen Fel d 4. J Mol Biol 2010; 401: 68–83.
- Spitzauer S, Schweiger C, Sperr W, et al. Molecular characterization of dog albumin as a cross-reactive allergen. J Allergy Clin Immunol 1994; 93: 614–27.
- Mattsson L, Lundgren T, Olsson P, et al. Molecular and immunological characterization of Can f 4: a dog dander allergen cross-reactive with a 23 kDa odorant-binding protein in cow Clin Exp Allergy 2010; 40: 1276–87.
- Mattsson L, Lundgren T, Everberg H, et al. Prostatic kallikrein: a new major dog allergen. J Allergy Clin Immunol 2009; 123: 362–8.
- Nilsson OB, Binnmyr J, Zoltowska A, et al. Characterization of the dog lipocalin allergen Can f 6: the role in cross-reactivity with cat and horse. Allergy 2012; 67: 751–7.
- Hilger C, Swiontek K, Arumugam K, et al. Identification of a new major dog allergen highly cross-reactive with Fel d 4 in a population of cat-and dog-sensitized patients. J Allerg Clin Immunol 2012; 129: 1149–1151.e2.
Common allergens in dog
Fungi
Fungi broadly divided into two groups based on their structure and include the unicellular yeasts, and the multicellular fungi that produce hyphae and spores. Although allergen-producing yeasts have been identified (e.g. Candida species, Malassezia species), most of the clinically important allergen-producing species are multi-cellular.
Multicellular fungi in Ascomycota and Basidiomycota phyla produce spores that are often found in very large quantities in the air. The size of spores vary between species, ranging from 1 to >100 μm. However, in general, most of the clinically important species produce spores in the range 7–12 μm.
Theoretically, fungal allergens should be more clinically significant because spores containing them are the most abundant airborne particles (e.g. >5,000 spores/m3) and are small enough to penetrate deep into the respiratory tree. This is in contrast to pollen grains. Meteorological studies reveal that atmospheric conditions such as wind speed, temperature, and humidity influence the release of spores.
Spore concentrations required to provoke symptoms will depend on the species (e.g. 50–100/m3 for Alternaria and 3,000/m3 for Cladosporium).
In a small number of people, symptoms of mold allergy may be brought on or worsened by eating certain foods such as cheeses processed with fungi. Occasionally, mushrooms, dried fruits, and foods containing yeast, soy sauce, or vinegar will produce allergy symptoms.
Molds can be found wherever there is moisture, oxygen, and a source of the few other chemicals they need. In the fall, they grow on rotting logs and fallen leaves, especially in moist, shady areas. In gardens or parks, they can be found in compost piles and on certain grasses and weeds. Some molds attach to grains such as wheat, oats, barley, and corn, which makes farms, grain bins, and silos likely places to find mold. Hot spots of mold growth in the home include damp basements and closets, bathrooms (especially shower stalls), places where fresh food is stored, refrigerator drip trays, house plants, air conditioners, humidifiers, garbage pails, mattresses, upholstered furniture, and old foam rubber pillows.
In general, Alternaria and Cladosporium (Hormodendrum) are the molds most commonly found both indoors and outdoors. Aspergillus, Penicillium, Helminthosporium, Epicoccum, Fusarium, Mucor, Rhizopus, and Aureobasidium (Pullularia) are common as well. Nevertheless, there is no relationship, however, between a respiratory allergy to the mold Penicillium and an allergy to the drug penicillin, which is made from mold.