Dog dander

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Dog serum albumin e221

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Code: e5
Latin name: Canis familiaris
Source material: Dander
Family: Canidae
Common names: Dog, Domestic Dog, Hound
Direct or indirect contact with animal allergens frequently causes sensitisation.
 
Animal allergens are major components of house dust.
 
Because of the close interrelationships of
  • Dog dander e5
  • Dog serum albumin e221

this single document will cover all of these allergens. The basic differences, to be described more fully further below, are the following:

Dog serum albumin is a protein mainly present in the serum. One exposure route is through saliva but  Dog serum albumin is also present in a fair amount in the skin (epithelium).
 
Dander is the material shed by the Dog into the environment through hair and “dandruff”. Dander is the “end product” and by far the most common source of Dog allergens and contains the highest proportion of dog specific allergens. It has naturally figured very prominently in clinical research, but  both allergen sources are important for an understanding of Dog allergy.

Allergen Exposure

Geographical distribution
The Dog, a relative of the Wolf, the Jackal, and the Fox, was one of the earliest domesticated animal, living in human communities as early as 12 000 years ago. Dogs remain pack animals and regard themselves as the lowest-ranking members of a human household. They are therefore very pliant in their behaviour and have been put to a great many uses, including herding, hunting, guarding, and pulling loads. More than 800 breeds have been developed according to human needs and preferences. Dogs are found in almost every human environment. In the industrialised world, they are nearly always companion animals, and because of their friendliness often live indoors and are frequently handled. There are around 68 000 000 owned Dogs in the United States alone.
 
Environment
Dogs are regularly found in households and on farms, but also in a feral state in cities and rural environments (though not in such large numbers as Cats). In the latter, they may form packs and become a danger to herd animals. Unvaccinated Dogs are also major spreaders of rabies.

Dog allergens have been found in serum, dander, pelt, hair and saliva, with the latter 4 being the most important, whereas Dog urine and faeces do not have any significant allergenic activity (1-3, 38, 44). (Extracts prepared from Dog liver, serum, salivary glands, and keratinocytes contain fewer IgE binding components (4).) Although allergen differences occur according to the origin of the allergen (e.g., epithelium or saliva), no breed-specific allergens occur (5, 6, 34, 38, 39). (This is contrary to much earlier studies (7, 8).) But the concentration of allergens varies within breeds and among them (44).
 
Animal dander is extremely light-weight and tiny in size (approx. 2.5 microns; 1 micron = 1/25 000 inch) and can stay airborne for hours. Dog and Cat serum albumin are very common allergens present in house dust, whereas Horse serum albumin is present only in the near vicinity of the animal (9). But it is important to note that allergen levels in air do not always correlate with those found in dust (10). Older animals produce more dander than younger ones, because their skin is drier. The epidermal turnover is more rapid in Dog breeds that are prone to the various forms of dry and oily seborrhoea. Instead of the normal 21-day cycle, the epidermal turnover time of seborrhoeic Dogs is 3 to 4 days. Dog epithelia IgE antibody concentration has been reported to show a seasonal variation although this might also be due to seasonal variation in testing  routines (11).
 
Levels of Dog allergen in houses with Dogs may reach high levels, usually over 10,000 ng Can f 1, the major dog allergen, allergen/g dust (12). Explained from another angle, exposure to Cat or Dog allergen airborne in homes with an animal can be up to 100 times higher than exposure to mite allergen (13, 14). Levels in homes without Dogs are generally 10 to 100 times lower but can still be detected.
 
Occasionally, high Dog allergen levels can be found in households without a pet, if the former occupants of the same household have had a pet, or if Dogs often visit the building (14). Similar findings have been reported from other studies. High levels of Can f 1 (> 10,000 ng) were found in dust in all but 1 of 50 homes with Dogs and in 8 of 50 homes without Dogs (28).
 
Airborne Can f 1 levels varied greatly among the homes with Dogs (range: 0.3 to 99 ng/m3). Approximately 50% of Can f 1 was shown to be carried on large particles, > 10 µm in diameter, and similarly to Cat allergen, approximately 20% was carried on particles < 4.7 µm in diameter. Airborne Can f 1 carried on small particles may remain airborne for long periods of time, unlike Dust mite allergen, which is carried on larger particles that fall rapidly to the ground after a disturbance (28).
 
In houses with Dog allergen, the highest concentration appears to occur on the living-room floor, on furniture, and in bedrooms. Dog allergens are however also prevalent on walls, smooth floors, and finished furniture in homes with and without pets (15). 
 
Washing the Dog achieves a modest reduction in the level of airborne Can f 1 in homes with a Dog. The Dog needs to be washed at least twice a week to maintain the reduction in recoverable Can f 1 from its hair (16).
 
Importantly, synthetic pillows have been reported to contain significantly more pet allergens than feather pillows, supporting the view that tightly woven encasements surrounding feather pillows act as a barrier against pet allergens (17).
 
Dog allergens can be detected not only in houses where Dogs are kept as pets, but also in other places such as schools and day-care centres where Dogs are not present on a regular basis (18-23). The allergens appear to be transported on clothes and may be present in relatively high concentrations (24). Furnishings and textiles in the classroom act as significant reservoirs of irritants and allergens and have an impact on the indoor air quality at school (25).
 
Concentrations of Can f 1 may be greater in dust collected in schools than in homes (26). In Sweden schools have been reported to be a major site of exposure to Cat and Dog allergens (27). In Swedish day-care centres, Dog allergen were shown to be present but usually at lower levels than in schools. In schools, the allergen levels ranged from 1700ng to 28200ng(Can f 1)/g dust on the chairs and 56 to 506ng/g on floors (19). Lower levels in day-care centres were explained by the fact that their floors were cleaned daily by wet sweeping (22).
 
Furthermore, it has been shown that upholstered seats in public places constitute a reservoir for the accumulation of Dog allergen, and a source of exposure to Can f 1 inside public buildings and on public transport (29). In a study of Helsinki City Transport buses, trams, and underground trains, which carry 687,000 passengers on a weekday, the median concentration of Can f 1 in dust from seats and floors in the vehicles was determined to be 2,400ng per g of dust (range 20 to 8,500 ng/g). Although these levels are not very high, they are high enough to cause symptoms in sensitive persons (30).
 
Even most automobile seats have been shown to have levels of Dog and Cat allergen that were well above the threshold levels considered to be risk factors for both sensitisation and symptoms, regardless of the presence of a pet in the home. The presence of live and dead mites and mite, Cat, and Dog allergens in automobiles and on clothing suggests that both are means of dispersal of mites and of mite and pet allergens (31).
 
Upholstered chairs in hospitals constitute a significant reservoir of Cat and Dog allergen, and inhalation of airborne allergen by patients attending their hospital appointments may exacerbate asthma in those highly allergic to Cats or Dogs (32).
 
In facilities used for Dog shows, the Dog allergen prevalence may be exceptionally high, up to 2,100,000ng Can f 1/g dust (33).
 
Unexpected exposure
Dog allergen particles can spread huge distances by many means, so that they can be found in practically any environment not specially sterilised. (See under Environment for examples.)
 
Allergens
As noted above, Dog allergens have early been detected in serum, dander, pelt, hair and saliva, with the latter 4 being the most important, whereas Dog urine and faeces seems to be less allergenic (1-3, 38, 44). (Extracts prepared from Dog liver, serum, salivary glands, and keratinocytes contain fewer IgE binding components (4).) Although allergen differences occur according to the origin of the allergen (e.g. dander, epithelium or saliva), no breed-specific allergens occur (5, 6, 34, 38, 39). (This is contrary to much earlier studies (7, 8).) But the concentration of allergens varies within breeds and among them (44).
 
Animal dander is not the hair or fur of the animal, but the particles, comprising mainly old skin scales, that are constantly shed. However, the term “dander” is not well defined (34). Dog hair and dander are complex mixtures of components (35). However, clean pure hair does not contain allergens. Early studies reported that 2 allergens were present in dander: a Dog-specific one and another cross-reacting with Cat epithelium. Both were present in the dander of dachshund, Airedale terrier, poodle and boxer (36). Since these early studies, over 24 antigens have been isolated from Dog dander extract, at least 7 of which are of allergenic importance. Some of these allergens have been identified as serum components such as albumin and gamma-globulin (37-39). The most important and specific allergen is the lipocalin Can f1.
 
Table 1
Dog allergens
 

Name

MW (kDa)

Main source

Function

Can f1

25

Dander, saliva

Lipocalin

Can f2

27

Dander, saliva

Lipocalin

Can f3

69

Serum, dander, epithelia, saliva, salivary gland, liver

Albumin

Can f4

18

Dander

 

 
In Dog hair/dander extracts, 2 IgE-antibody-binding components with molecular masses of 23 kDa and 19 kDa have been isolated. These were designated Can d 1 and Can d 2, respectively, and were found in sera of approximately 74% of Dog-allergic individuals (39). These have since been renamed Can f 1 and Can f 2.
 
In another study, sera from 96% of patients with Dog allergy demonstrated specific IgE to these allergens. Can f 1 was preferentially detected in the (dander) extract and saliva, but not in skin, salivary gland, serum and liver extracts. Can f 2 was strongly expressed in skin, but not in dander, serum and liver (40, 41).  
 
Can f 1 is a major allergen and the most important Dog allergen, and Dog dander and saliva have a high content of it (38, 42-44). The protein is produced in the canine Von Ebner’s glands, which are small lingual salivary glands opening in the lingual epithelium. This protein actually ranges from 21 kDa to 25 kDa and is found in dander and saliva, but not in serum, and is a lipocalin (45, 46). Dog urine and faeces contain very little of this allergen (44, 47). More than 90% of Dog-allergic patients have been shown to have specific IgE directed to this allergen (42, 44) (48-49). Can f 1 was originally named Ag13 and found to be identical to Ag8 (44).
 
It was also, as mentioned above, previously known as Can d 1. Can f 1 has demonstrated greater heat resistance than mite allergens after 60 min at 140 degrees C (50). The protein is also relatively stable in house dust (49).
 
Can f 2, previously known as Can d 2, a protein with a molecular weight of 19 kDa (39) or 27 kDa (47) is found in dander and saliva (39, 47). It is a lipocalin and has homology with Mouse urinary protein (MUP) (44, 48, 51). Human IgE binding studies have confirmed the relevance of this allergen. It was found to react with IgE antibodies of 66% of Dog-allergic patients, and to bind 23% of the IgE antibodiesdirected against Dog dander extract, confirming its role as a minor allergen (44).
 
Can f 3, Dog serum albumin, a 69 kDa protein, is found in dander, hair, epithelia, saliva, and serum (52, 53). It has also been found in salivary glands (parotid and submandibular) and liver (39). In one study, up to 90% of Dog-specific IgE antibodies were directed to Dog albumin in sensitised patients (4). This is in contrast with a study that reported that in 203 asthmatic children studied with regard to Dog serum albumin allergenicity, significant skin-specific IgE antibodies to Dog serum albumin were detected in only 9 of the 80 subjects who had significant skin-specific IgE to Dog dander and hair (54). Similarly, in 70 Dog-allergic subjects, serum-specific IgE to Dog serum albumin was found in approximately 40% (39). Dog serum albumin has also been reported to be an abundant allergen in Dog epithelia extracts (55). In 49 subjects hypersensitive to Cats and/or Dogs, serum albumin elicited intracutaneous reactions in most, but gave positive nasal provocation and RAST results in only a few and was, therefore, reported to be of limited clinical importance (1). Other studies have reported this allergen to be a minor allergen (39, 56).
 
Can f 4 is an allergen found in Dog dander.
 
Two serum proteins, alpha-1-antitrypsin and IgG, have been identified as minor allergens (2).
 
A distinct 19 kDa protein allergen has also been described (57).

Potential Cross-Reactivity

An extensive cross-reactivity among the different breeds of Dog could be expected.
 
Frequently, clinical observation has noted that many patients allergic to Cats are also allergic to Dogs. Many studies suggest evidence for cross-reactivity between some Cat and Dog allergens: in an early RAST inhibition study, significant cross-reactivity was observed between Cat hair and Dog dander, but saliva and urine were shown to be more species-specific (58). 
 
Among 109 patients with animal allergy, allergens of similar molecular weight were detected in sera from 68 patients with both Cat and Dog allergy. Common as well as species-specific IgE epitopes of the major Cat and Dog allergens could be demonstrated by IgE inhibition studies. The authors concluded that shared IgE epitopes of the major Cat and Dog allergens may provide an explanation for the clinical observation that allergies to Cats and Dogs are frequently associated (59). 
 
However, several studies report an actual common allergen or allergens as responsible for the cross-reactivity, and these allergens appear to be serum albumin and lipocalin.
 
In a study reporting that Dog dander-specific IgE antibodies were inhibited by Cat epithelium allergens, 2 allergens were detected - one closely related to the major Cat epithelium allergen, the other Dog-specific. Both were present in the dander of dachshund, Airedale terrier, poodle and boxer (36). Other studies have concurred, and attributed the cross-reactivity to a 69 kDa protein common to both (60). This protein was probably what is recognised today as serum albumin.
 
Albumins occur at high concentrations in animal hair/dander extracts and represent important cross-reactive allergens for up to 35% of patients with animal allergy (4) (58). Although, being a minor allergen i.e. present in a low percentage of patients, sera from patients who are sensitised against albumins often contain a high percentage of albumin-specific IgE. Cat and Dog albumins are minor cross-reacting allergens that share a high degree of homology and cause sensitisation in 14% - 23% and 35% of Cat and Dog allergic patients respectively, and this may help explain the Cat-Dog cross-reactivity phenomenon (4, 58). Significant sequence homologies of greater than 75% were found with albumins from different species: human, Pig, Cattle, Sheep, Mouse and Rat. The presence of common IgE-reactive epitopes among the major Cat and Dog allergens explains why many patients with animal allergies react to Cat and Dog hair/dander extracts (58).
 
In IgE immunoblot inhibition studies and histamine release tests, it has been demonstrated that patients who react to Dog albumin exhibit IgE reactivity with purified albumins from Cat, Mouse, Chicken, and Rat. The proportion of Dog-specific IgE directed against Dog albumin was determined for patients allergic to Dog albumin, and it was found to range from 70% to 90%. The deduced amino acid sequence of this protein was compared with the Swiss-Prot library, and significant sequence homologies were found with albumins from different species (human: 82.6%, Pig: 81.8%, Cattle: 77.3%, Sheep: 78.8%, Mouse: 75.8%, and Rat: 76.2%) (4).
 
Individuals clinically allergic to Horse could be sensitised to Horse serum albumin. These anti-horse albumin  antibodies may cross react with Dog serum albumin as well as other serum albumins from different origins (9). In a study assessing the importance of albumin as a cross-reactive allergen in patients sensitised to Cat, Dog and horse, 117 patients sensitised to Cat were tested for IgE reactivity using skin-specific IgE determination and RAST assays with Cat, Dog and Horse hair/dander extracts and their purified albumin extracts. Twenty-two percent of patients exhibited specific IgE to Cat albumin; 41% of patients sensitised to Cat were also sensitised to Dog and Horse. Of these patients, 21% had IgE antibodies to 3 albumins and 17% to 2. IgE binding to Horse extract was inhibited to 30% by its homologous albumin, and IgE binding to Cat and Dog extracts almost to 15% by their respective albumins. The study concluded that albumins from these 3 animals share some epitopes that account for the cross-reactivity observed in around one third of patients sensitised to Cat, Dog and Horse. However, more than 50% of specific IgE that cross-reacted among these 3 animals was directed to allergens other than albumin (61). Other studies have investigated Horse-Dog cross-reactivity and concluded that there was extensive but variable degrees of cross-reactivity between serum albumins, including human albumin (53).
 
Cross-reactivity has been described between Pork and Cat epithelia and attributed to serum albumin. In that report, the authors described anaphylaxis in an individual following consumption of wild boar meat (62).
 
Major respiratory allergens of Dogs, Mice, Rats, Horses and Cows belong to the lipocalin group of proteins. The sequence identity of lipocalins is often less than 20%, but they contain between 1 and 3 structurally conserved regions, and their 3-dimensional structures are similar (46). The Cat allergen cystatin (Fel d 3), a cysteine protease inhibitor, was shown to have the cysteine protease inhibitor motif also partially conserved in the Dog allergen sequences Can f 1 and Can f 2, which are lipocalins (51).
 
Allergens with the same molecular weight have been determined in Mink, Blue Fox, Silver Fox, Raccoon, Dog, and Fitchew fur and urine extracts. Common IgE-binding epitopes, probably common allergens (especially the 62-67 kDa bands), have been suggested. IgE binding to the allergenic bands of these fur animal extracts was also observed in immunoblotting studies when Dog- and Cat-specific IgE-positive sera were used, and further inhibition studies of Dog-positive sera with fur animal extracts and fur-positive sera with Dog extract confirmed cross-reactivity of these IgE antibodies (63).

Clinical Experience

IgE-mediated reactions
The association between pet exposure and asthma or sensitisation can be very confusing, and many conflicting findings have been published (64). Recent studies can be used to support just about any viewpoint on the issue: Dog exposure decreases (65, 66), or has no effect (67) on the risk of sensitisation; asthma is negatively (67) or positively (68)  associated with Dog exposure. Furthermore, Dog (and Cat) allergen is ubiquitous in human society and may affect sensitisation in predisposed individuals regardless of pet ownership (64, 69, 70). It has been suggested that exposure before birth or in early childhood is crucial in the process of sensitisation (71). In studies where early-life exposure to pets, or lifestyle factors associated with exposure to pets, were reported to reduce the risk of developing atopy-related diseases in early childhood, these findings may also be explained by selection for keeping pets (72).
 
Nevertheless, Dog dander clearly represents an important source of inhalant allergens, and many studies report that Dog may frequently induce symptoms in sensitised individuals (40, 41, 49, 60). Symptoms include asthma, allergic rhinitis and allergic conjunctivitis. Thirty to 35% of atopic individuals display type I allergic symptoms on exposure to Cat and/or Dog allergens (4, 73, 74).
 
Fifteen percent of Finnish adolescents were reported to be sensitised to Dogs (75). In Los Alamos, New Mexico, 67% of asthmatic children were sensitised to Dog allergens (76). Specific IgE to Dog has been reported detected in up to 67% of asthmatic children (76), and among children with asthma, 40% were shown to have skin-specific IgE to Dog dander even though they had no direct contact with Dogs (75).
 
Importantly, symptoms can be caused by indirect exposure to Dog dander in schools, at work, and on public transport. Dog allergen can be transferred on a pet owner’s clothes and cause symptoms in an allergic person sitting nearby. In sensitised subjects, repeated exposure to allergens also contributes to subclinical inflammation, hyperresponsiveness, and general worsening of asthma (77, 78).
 
Also importantly, Dog-allergic people may also be allergic to Cat: Cat allergen-specific serum IgE antibodies were detected in 71% of a group of 38 Dog dander-sensitive patients (36). Asthmatics sensitised to Cat and Dog have been shown to often also be sensitised to many other allergens (79).
 
Dermatitis following exposure to Dog allergens has been reported (80).
 
Occupational allergy to Dog allergens may also occur in animal workers, animal pelt workers, and laboratory workers. In a large epidemiological study of 5,000 laboratory workers, symptoms were reported in 26% exposed to Mice, 25% to Rats, 31% to Guinea Pigs, 30% to Rabbits, 26% to Hamsters, 25% to Dogs, 30% to Cats and 24% to Monkeys (81).
 
Interestingly, in Swedish farming households, in spite of the abundance of Can f 1, farmers were sensitised to Dogs only to a low degree (82).
 
Hand dermatitis in veterinarians has been reported (83).
 
Contamination of commercially available Dog dander skin-specific IgE preparations with the major allergens (Der p 1 and Der p 2) of the House Dust mite (D. pteronyssinus) has occurred, resulting in false-positive responses (84), showing the importance of using pure allergen source materials.
 
The effect of Dog avoidance on Dog dander-specific IgE antibody levels was studied from sera obtained from 24 subjects. Steadily high and even rising levels were observed in cases when a strict avoidance of Dogs was reported by the patient (85).
 
Compiled by Dr Harris Steinman, harris@zingsolutions.com

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As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.