rCan f 5 Dog (plus rCan 1,2,3)

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Code: e226
Latin name: Canis familiaris
Source material: rCan f 5 is a CCD-free recombinant protein

Dog allergen components

  • rCan f 1 e101
  • rCan f 2 e102
  • rCan f 5 e226

Native allergens

nCan f 3 - Dog serum albumin e221


The dog is a relative of the wolf, the jackal, and the fox; all belong to the family Canidae. Two characteristics distinguish the dog from other canids: its worldwide distribution in close association with humans, and its huge variety as a result of adaptation and breeding for specific purposes. Over the centuries dogs have acquired the body types and dispositions to pursue and retrieve game, and to be draught animals, guides (e.g. for the blind), guards, companions, and so on. 

Dogs are found in almost every human environment. Some dogs are feral, but not in such large numbers as cats are.

As with cat, major dog allergens can be found in hair, dander, pelt, saliva and serum, and are considered epithelial allergens; unlike with cat, however, dog urine and faeces do not have any significant allergenic activity. (1, 2, 3, 4, 5) The concentration of allergens varies between and within breeds. (2, 6) Although allergen differences occur according to the source of the allergen (e.g. epithelium or saliva), no breed-specific allergens occur. (7, 8) This is contrary to reports of much earlier studies. (9, 10)

Dog allergens are ubiquitous in the environment. For example, they may be found on automobile seats in concentrations well above the thresholds for both sensitisation and symptoms, regardless of the presence of a pet in the home. (11) Dog allergens are also prevalent on walls, smooth floors, and finished furniture in homes with and without pets, (12) as well as on furnishings and textiles in classrooms. (13, 14) The concentration of dog (Can f 1) allergen may be even higher in dust collected in schools than in that collected in homes. (15) High dog allergen levels can be found in households without a pet if the former occupants had a pet, or if dogs often visit the building. (16)

Upholstered chairs in hospitals constitute a significant reservoir of cat and dog allergens, and inhalation of airborne allergens by patients attending their hospital appointments may exacerbate asthma in those highly allergic to cats or dogs. (17)

The association between pet exposure and asthma or allergic sensitisation can be very confusing, and many conflicting findings have been published. (18) Recent studies can be used to support nearly any viewpoint on the issue: Dog exposure decreases (19, 20) or has no effect (21) on the risk of sensitisation; asthma is negatively (21) or positively (22) associated with dog exposure. What makes certainty impossible is that dog (and cat) allergens are ubiquitous in human society and may affect sensitisation in predisposed individuals, regardless of pet ownership. (18, 23, 24)

Nevertheless, dog dander clearly represents an important source of inhalant allergens, and many studies report that dog may frequently induce symptoms in sensitised individuals. (1, 25, 26, 27) 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. (28, 29, 30) Furthermore, occupational allergy to dog allergens may occur in animal workers, animal pelt workers, and laboratory workers. (31)

Early studies reported that over 28 dog antigens were detected, 11 of which were found in dog serum. IgE antibody in the sera of dog-sensitive patients was reported to bind to 21 of these antigens to varying degrees. (3,)  (4)

The following allergens have been characterised:

  • Can f 1, a lipocalin. (2, 32 ,33, 34, 35, 36, 37)
  • Can f 2, a lipocalin. (2, 32, 33, 35, 37)
  • Can f 3, dog serum albumin. (28, 35, 38)
  • Can f 4, an 18 kDa protein, an odorant binding protein. (33, 35, 39)
  • Can f 5, also known as prostatic kallikrein, an arginine esterase. (35, 40, 41, 42, 43)

Two serum proteins, alpha-1-antitrypsin and IgG, have been identified as minor allergens. (8)

  • Can f 1 was originally named Ag13 and was found to be identical to Ag8. (2) Can f 1 is a 22 to 25 kDa protein found in hair, dander and saliva, but not in serum, and is a lipocalin family member. (32)

    The amount of dog allergens produced appears to have wide variability among dog breeds. Hair length or hormonal status does not influence the production of Can f 1 (except that males produce more than females), whereas seborrhoea strongly influences the presence of Can f 1 on hair. (2) Older animals produce more dander than younger ones, because their skin is drier. Also, 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 only 3 to 4 days.
     
  • Can f 2, a 19 kDa protein found in dander and saliva, and previously known as Can d 2, is a lipocalin family member and has homology with mouse urinary protein (MUP). (32, 44) In the majority of studies, it is shown to be a minor allergen.
     
  • Can f 3, dog serum albumin, a 69 kDa protein, is found in dander, epithelia, saliva, and serum. (37) It has also been found in salivary glands (parotid and submandibular) and liver. (45) Dog albumin represents an important allergen for up to 35% of patients who are allergic to dogs. (28)
     
  • Can f 4 is an allergen found in dog dander.
     
  • Can f 5, prostatic kallikrein, is found in dog urine, and a closely related or identical protein in dog dander. (39)

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. (46) However, several studies report that actual common allergens are responsible for the cross-reactivity, and that these allergens appear to be serum albumin and lipocalin. Furthermore, in a study of 36 cat-allergic patients, in 25% of Fel d 1-reactive patients more than 50% inhibition of IgE reactivity to dog allergens was achieved with recombinant Fel d 1. A Fel d 1 cross-reactive 20 kDa allergen was detected in dander extracts of several different dog breeds, which may be responsible for double positivity to cat and dog in serology. However, the clinical relevance of this cross-sensitisation was not clinically evaluated. (47)

Importantly, dog-allergic individuals are sensitised to a heterogeneous range of dog allergens. For example, in a study of such individuals, 52% were shown to be sensitised to Can f 1, about 33% to Can f 2, 60% to an 18 kDa protein, 44% to a 40 kDa protein, and 48% to a 70 kDa protein (probably serum albumin, now known as Can f 3). (33)

A second study (evaluating Can f 5) illustrates the heterogeneity of allergen sensitisation, in which recombinant Can f 5 was shown to bind IgE antibodies from 26 (70%) of 37 sera of subjects with dog allergy, 14 of which reacted to none of Can f 1, Can f 2, or Can f 3. (39) Of 37 sera of subjects with dog allergy, 26 (70%) showed IgE reactivity to recombinant Can f 5, and 18 (49%) to rCan f 1. Both rCan f 2 and nCan f 3 appeared as minor allergens among the subjects studied, binding IgE antibody from only 8 (22%) and 6 (16%) respectively. Fourteen (38%) of the 37 sera reacted to rCan f 5 alone. (39) Only 2 of the 37 sera tested showed no IgE reactivity to any of the 4 dog allergens tested.

Recombinant allergens (which are genetically engineered isoforms resembling allergen molecules from known allergen extracts) have immunoglobulin E (IgE) antibody binding comparable to that of natural allergens, and generally show excellent reactivity in in vitro and in vivo diagnostic tests. (48 )To date, many different recombinant allergens of various pollens, moulds, mites, and foods (as well as allergens of latex and bee venom) have been cloned, sequenced, and expressed.

Recombinant allergens have a wide variety of uses, from the diagnosis and management of allergic patients, to the development of immunotherapy, to the standardisation of allergy test products as tools in molecular allergology. Recombinant allergens are particularly useful for investigations of allergies manifesting wide cross-reactivity.


rCan f 1

Allergen

rCan f 1. (32, 33, 37, 49)

Allergen source material

An E. coli strain carrying cloned cDNA encoding Canis familiaris allergen Can f 1. 

Common names

Ag 13.

Biological function

Can f 1 is a lipocalin.

Mw
22-25 kDa.

Allergen description

Can f 1 (originally designated Can d 1) is a lipocalin. Can f 1 is a major allergen and the most important dog allergen, and dog dander and saliva have a high Can f 1 content (though serum has none). The protein is produced in the canine Von Ebner’s glands, which are small salivary glands opening in the lingual epithelium. This protein ranges in size from 21 kDa to 25 kDa. (50, 51) Can f 1 has demonstrated greater heat resistance than mite allergens after 60 minutes at 140°C. (16) The protein is also relatively stable in house dust. (26)

Major respiratory allergens of dogs, mice, rats, horses and cows belong to the lipocalin group of proteins. The amino acid sequence identity between lipocalins is often less than 20%, but they contain between 1 and 3 structurally conserved regions, and their 3-dimensional structures are similar. Lipocalins share certain biological functions, predominantly related to the transport of small hydrophobic molecules such as vitamins and pheromones.

Immune reactivity to lipocalin allergens is not well understood. In Bos d 5, the IgE-binding epitopes are spread along the molecule, whereas in Bos d 2, the C terminus appears to contain the human B cell epitopes. Bos d 5 contains several murine T-cell epitopes. To explain these observations, it has been proposed that the allergenicity of lipocalins may be a consequence of molecular mimicry between lipocalin allergens and endogenous lipocalins at the T-cell level. (51)

Can d 1 and Can d 2 are found in the sera of approximately 74% of dog-allergic individuals. (44) More than 90% of dog-allergic patients have been shown to have specific IgE directed to Can f 1 alone. (2, 32, 52, 53) In another study, sera from 96% of patients with dog allergy demonstrated specific IgE to Can f 1 and Can f 2. Can f 1 was preferentially detected in dander 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. (1, 25) However, not all studies have found a high prevalence of IgE reactivity in dog-allergic patients; one study reported that, according to ELISA determination, 52% of dog-allergic patients recognised recombinant Can f 1. (33) The authors postulated that this may have been due to their selection of patients, but it has not been determined whether certain populations are less frequently sensitised to Can f 1.

Recombinant Can f 1 and Can f 2 are immunologically concordant with natural Can f 1 in serum- and skin-specific IgE analysis. The concordance is slightly lower with recombinant Can f 2. Fifty-two percent of dog-allergic patients reacted against Can f 1, and about a third of the patients reacted to Can f 2. (33)

As the important allergens in commercial dog extracts can vary extensively, and as natural preparations may be contaminated with Mite allergens, potentially causing false-positive skin-specific IgE test results, recombinant Can f 1 and recombinant Can f 2 have a role to play in assessing allergy to dog. (54)

Can f 1 and 2 are two important and useful tools identified so far, but further components are needed for diagnosing dog allergy. (33)


rCan f 2

Allergen
rCan f 2. (32, 33, 37, 48) 

Allergen source material
An E. coli strain carrying a cloned cDNA encoding Canis familiaris allergen Can f 2. 

Common names

None. 

Biological function

Can f 2 is a lipocalin. 

Mw

19 kDa. 

Allergen description

Can f 2, previously known as Can d 2, is a protein with a molecular weight of 19 kDa (44) or 27 kDa. (4) It is a lipocalin and has homology with mouse urinary protein (MUP). (2) It was found to react with IgE antibodies of 66% of dog-allergic patients, and to bind 23% of the IgE antibodies directed against dog dander extract, both of which findings confirm its role as a minor allergen. (2) Recombinant Can f 2 has a slightly lower concordance compared to natural Can f 2, with about a third of dog-allergic patients found to be sensitised to this recombinant allergen. (33) Can f 1 and Can f 2 share epitopes. (49)

A study evaluated the recombinant Dog allergens Can f 1 and Can f 2 in clinically diagnosed dog-allergic patients and in healthy, non-atopic dog owners. These allergens were compared to commercial dog epithelial extract, and it was found that patients' IgE reactivity to natural Can f 1 and to the recombinant allergen were perfectly concordant, but the concordance was slightly lower with recombinant Can f 2. About one-third of the patients reacted to Can f 2. The study concluded that the recombinant allergens can be used reliably to identify Can f 1 and Can f 2-sensitised individuals, but that on their own the 2 allergens were insufficient as reagents for diagnosing dog allergy. (33)


nCan f 3 - Dog serum albumin e221 

Allergen

nCan f 3. (3, 8, 10, 28, 37, 35, 53, 55, 56, 57, 58) 

Allergen source material

Native dog serum albumin 

Common names

Dog serum albumin, DSA. 

Biological function

Can f 3 is a serum albumin. 

Mw

69-70 kDa. 

Allergen description

Can f 3, also known as Dog Serum Albumin (DSA), is a protein with a molecular weight of 69-70 kDa. It is a serum albumin. It is found in dog serum, saliva, dander, hair and epithelia, and it is also synthesised in the dog salivary gland and dog liver. (37) Dog serum albumin has been reported to be a particularly abundant allergen in dog epithelia extracts. (55) Dog and cat serum albumins are also allergens very commonly present in house dust. (44) A recombinant Can f 3 has been produced. (37)

Sensitisation to dog serum albumin has previously been documented as varying from around 35-48%, although early studies reported even lower frequencies. (5, 28, 33, 59) The importance and frequency of sensitisation to DSA also varies in different populations. (3)

In a study, 51 patients with a clinical history of dog allergy were evaluated for skin-specific IgE for 8 individual, standardised dog breed allergen preparations, and for 1 mixed-breed allergen preparation, dog serum albumin, and histamine hydrochloride. The sensitivity rate shown by skin-prick test was 67% to 88% for the various dog breed allergen preparations, but only 18% for DSA. (10)

The deduced amino acid sequence of DSA was shown to be highly homologous to the sequences of albumins from both other animals and humans, which explained the perceived extensive cross-reactivity among albumins, and was corroborated by the demonstration of the presence of similar epitopes on dog, cat, and human albumin. (37) In immunoblot inhibition studies and histamine release tests, it was demonstrated that patients who react to Dog albumin exhibit IgE reactivity with purified albumins from cat, mouse, chicken, and rat. The deduced amino acid sequence of DSA was found to have significant sequence homology with albumins from human (82.6%), pig (81.8%), beef (77.3%), sheep (78.8%), mouse (75.8%), and rat (76.2%). (28)

Cross-reactivity between DSA and albumins from other animals was demonstrated in other studies. In a study aimed at 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 the presence of skin- and serum-specific IgE. Twenty-two percent of patients were found to have specific IgE to cat albumin, and 41% of these patients were also sensitised to dog and horse. Of this group, 21% had IgE to all 3 albumins and 17% to 2. However, inhibition studies demonstrated variable degrees of inhibition, suggesting that albumins from these 3 animals share some epitopes that account for the cross-reactivity observed in around a third of patients sensitised to cat, dog and horse, but that more than 50% of specific IgE that cross-reacts between these 3 animals is directed to allergens other than albumin. (60)

Similarly, in a study evaluating the degree and significance of IgE-cross-reactivity to various albumins in 200 patients allergic to animals, it was found that approximately 30% of those allergic to animal hair/dander extracts reacted to albumins from various animals. Although a high degree of sequence homology existed between different animal albumins, a remarkable variability of IgE cross-reactivity was observed, indicating that some patients were sensitised preferentially against certain albumins. Most of the patients allergic to albumins reacted to dog, cat, and horse albumin, which also bound a high percentage of albumin-specific IgE. Recombinant dog albumin fragment, representing 265 amino acids of the mature protein, bound IgE from all 15 patients allergic to albumin who were tested. (61)

An association between allergy to epithelia and allergy to mammalian meat has also been reported, and most authors ascribed this to serum albumin as the responsible cross-reacting allergen. For example, a 28-year-old asthmatic male cook sensitised to dog epithelium was reported who developed wheezing and contact urticaria when handling raw beef in an occupational setting. Skin-specific IgE was found to raw and cooked beef and raw lamb, and to cat and dog. Dog serum-specific IgE was positive. The secondary cross-reactivity was attributed to Bovine Serum Albumin (BSA). (62)

Furthermore, patients with persistent milk allergy and specific IgE to BSA were reported to be at greater risk of rhinoconjunctivitis and asthma because of cross-reactivity with serum albumin present in animal dander. In a study evaluating the cross-reactivity between the serum albumin of various mammals in milk, meat, and epithelia, sera from all but 1 patient recognised serum albumin in cow’s milk, in meat from beef, lamb, deer, and pork, and in epithelia from dog, cat, and cow. Some patients were sensitised only to serum albumin in meat and epithelia. Patients allergic to only dander recognised other proteins in epithelia, but not serum albumin. The authors concluded that serum albumin is an important allergen in cow’s milk, meat, and epithelia allergy. The authors proposed that sensitisation first occurs by contact with serum albumin in cow's milk and that patients develop sensitisation to serum albumin present on animal epithelia, even without direct contact with animals. The authors cautioned that patients with both BSA and cow's milk allergy must avoid raw meats and furry pets. (63)

Although studies have demonstrated a high degree of homology among serum albumins from various mammals, epitope diversity results in different clinical expressions of cross-reactivity. This is particularly well described in pork-cat cross-reactivity, where cross-reactivity has been demonstrated between pork meat and cat epithelia as a result of serum albumin, but not with dog. (64, 65)

Dog serum albumin may be used for diagnostic purposes to identify patients who are cross-sensitised to many animal species, and may perhaps be used for specific immunotherapy for sensitised individuals. (37)


rCan f 5 

Allergen

rCan f 5. (39) 

Allergen source material

A Pichia pastoris strain carrying a cloned cDNA encoding Canis familiaris allergen Can f 5. 

Common names

Prostatic kallikrein, also known as urinary kallikrein or arginine esterase. 

Biological function

Can f 5 is an arginine esterase. 

Mw

28 kDa 

Allergen description

Can f 5, also known as prostatic kallikrein, is a protein with a molecular weight of 28 kDa. The unreduced 28 kDa band appears to be made up of an 18 and a 10 kDa protein. It is an arginine esterase found in dog urine, with a similar or identical protein in dander. (39) A recombinant Can f 5 displaying immunologic and biochemical properties similar to those of the natural protein has been produced. (39)

Prostatic kallikrein has been described as an androgen-regulated protein expressed in the prostate (Chapdelaine 1988 ref. 26113 7), (66) suggesting an occurrence restricted to male animals. Castrated male dogs have been found to have drastically reduced production of prostatic kallikrein. (66) Can f 5 was characterised utilising urine collected from an adult, intact male dog. (39)

This suggests that subjects with dog allergy (depending on their specific sensitisation profile) might be differently sensitive to male and female dogs – in particular for patients sensitised exclusively to Can f 5, as were one-third of the subjects in this particular study. (39) And as male dog castration practice may vary between countries and regions, the importance of allergy to Can f 5 may differ accordingly. Importantly, commercially-available dog dander comprises material from a pool of male and female dogs of different breeds. (39) A simple experiment could not detect Can f 5 from the dander of a female dog, although Can f 1 was readily detected. (39) The authors speculated as to how prostatic kallikrein becomes deposited on dog hair or dander, and whether prostatic kallikrein is consistently absent from the hair and dander of female dogs.

Can f 5 is shown to be a major allergen. Recombinant Can f 5 was shown to bind IgE antibodies from 26 (70%) of 37 sera of subjects with Dog allergy, 14 of which reacted to none of Can f 1, Can f 2, or Can f 3. (39)

Of 37 sera of subjects with Dog allergy, 26 (70%) showed IgE reactivity to recombinant Can f 5, and 18 (49%) to rCan f 1. Both rCan f 2 and nCan f 3 appeared as minor allergens among the subjects studied, binding IgE antibody from only 8 (22%) and 6 (16%) respectively. Fourteen (38%) of the 37 sera reacted to rCan f 5 alone. (39) Only 2 of the 37 sera tested showed no IgE reactivity to any of the 4 dog allergens tested.

On average, in all rCan f 5-reactive sera, the level of IgE-antibody binding to rCan f 5 amounted to 54% of that to dog dander. The corresponding relative levels of IgE antibody binding to rCan f 1, rCan f 2, and nCan f 3 were 45%, 25%, and 47% respectively among sera specifically reactive to those allergens. (39)

Dog prostatic kallikrein (Can f 5) shares structural similarity (55% to 60% sequence identity) with human prostate-specific antigen (PSA). (39) PSA which is present in seminal plasma has been shown to be a key culprit in IgE-mediated vaginal reactions to semen. (67, 68) The binding of PSA to IgE antibody from a patient with allergic reactions to human semen has been demonstrated. (67) Similar results were reported: four PSA-reactive sera were identified and used in IgE inhibition experiments; IgE antibody binding to PSA was extensively inhibited by the dog allergen in 2 of the 4 sera (88% and 98% respectively), whereas partial inhibition (60%) was obtained in 1 serum and no inhibition occurred in 1 serum. Control experiments demonstrated that the IgE inhibition activity of recombinant Can f 5 was immunologic and specific. (39)

It is therefore possible that infertility in humans may be as a result of IgE-mediated reactions to Can f 5. (39)

Although dog prostatic kallikrein shows an intermediate level of sequence conservation (53% to 59% sequence identity) with other members of the same protein family from different species (cow, horse, rat, rabbit, mouse, and guinea pig), a certain degree of cross-reactivity may exist; but the extent of the clinical relevance has not yet been evaluated. (39)

Can f 5 may be used for component-resolved diagnostic purposes for dog allergy, and possibly to identify patients who are cross-sensitised to PSA and experiencing allergic vaginal reactions to human semen and complications caused by that condition, and perhaps may be used for specific immunotherapy for sensitised individuals. (37)

Compiled by Dr Harris Steinman, harris@allergyadvisor.com 

References

  1. Spitzauer S, Rumpold H, Ebner C, Schweiger C, Valenta R, Gabl F, Anrather J, Breitenbach M, Scheiner O, Kraft D. Allergen profiles of dog hair and dander, body fluids and tissues as defined by immunoblotting. Int Arch Allergy Appl Immunol 1991;94(1-4):346-8.
  2. De Groot H, Goei KGH, van Swieten P, Aalberse RC. Affinity purification of a major and a minor allergen from dog extract: serologic activity of affinity-purified Can f I and of Can f I-depleted extract. J Allergy Clin Immunol 1991;87:1056-65.
  3. Ford AW, Alterman L, Kemeny DM. The allergens of dog. I. Identification using crossed radio-immunoelectrophoresis. Clin Exp Allergy 1989;19:183-90.
  4. Ford AW, Kemeny DM. The allergens of dog. II. Identification and partial purification of a major dander allergen. Clin Exp Allergy 1992;22(8):793-803.
  5. Brehm K, Plock K, Doepp M, Baier H. Antigenicity of serum albumin in allergy against cat or dog epithelium (significance of the radioallergosorbens test in the diagnosis of allergies). [German] Dtsch Med Wochenschr. 1975;100(10):472-6.
  6. Ramadour M, Guetat M, Guetat J, El Biaze M, Magnan A, Vervloet D. Dog factor differences in Can f 1 allergen production. Allergy 2005;60(8):1060-4.
  7. Wüthrich B, Guerin B, Hewitt BE. Cross allergenicity between extracts of hair from different dog breeds and cat fur. Clin Allergy 1985;15(2):87-93.
  8. Blands J, Løwenstein H, Weeke B. Characterization of extract of dog hair and dandruff from six different dog breeds by quantitative immunoelectrophoresis. Identification of allergens by crossed radioimmunoelectrophoresis (CRIE). Acta Allergologica 1977;32:147-69.
  9. Moore BS, Hyde JS. Breed-specific dog hypersensitivity in humans. J Allergy Clin Immunol 1980;66(3):198-203.
  10.  Lindgren S, Belin L, Dreborg S, Einarsson R, Pahlman I. Breed-specific dog-dandruff allergens. J Allergy Clin Immunol 1988;82(2):196-204.
  11. Neal JS, Arlian LG, Morgan MS. Relationship among house-dust mites, Der 1, Fel d 1, and Can f 1 on clothing and automobile seats with respect to densities in houses. Ann Allergy Asthma Immunol 2002;88(4):410-5.
  12. Arlian LG, Neal JS, Morgan MS, Rapp CM, Clobes AL. Distribution and removal of cat, dog and mite allergens on smooth surfaces in homes with and without pets. Ann Allergy Asthma Immunol 2001;87(4):296-302.
  13. Smedje G, Norback D. Irritants and allergens at school in relation to furnishings and cleaning. Indoor Air 2001;11(2):127-33.
  14. Dybendal T, Vik H, Elsayed S. Dust from carpeted and smooth floors. II. Antigenic and allergenic content of dust vacuumed from carpeted and smooth floors in schools under routine cleaning schedules. Allergy 1989;44:401-11.
  15.  Lonnkvist K, Hallden G, Dahlen SE, Enander I, van Hage-Hamsten M, Kumlin M, Hedlin G. Markers of inflammation and bronchial reactivity in children with asthma, exposed to animal dander in school dust. Pediatr Allergy Immunol 1999;10(1):45-52.
  16.  Custovic A, Simpson B, Simpson A, Hallam C, Craven M, Woodcock A. Relationship between mite, cat, and dog allergens in reservoir dust and ambient air. Allergy 1999;54(6):612-6.
  17. Custovic A, Fletcher A, Pickering CA, Francis HC, Green R, Smith A, Chapman M, Woodcock A. Domestic allergens in public places III: house dust mite, cat, dog and cockroach allergens in British hospitals. Clin Exp Allergy 1998;28(1):53-9.
  18. Almqvist C, van Hage-Hamsten M. Cat and dog allergens - can intervention studies solve their inscrutable riddle? Clin Exp Allergy 2003;33(9):1167-70.
  19. Ownby DR, Johnson CC, Peterson EL. Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age. JAMA 2002;288:963-72.
  20. Almqvist C, Egmar AC, Hedlin G, Lundqvist M, Nordvall SL, Pershagen G, Svartengren M, van Hage-Hamsten M, Wickman M. Direct and indirect exposure to pets - risk of sensitization and asthma at 4 years in a birth cohort. Clin Exp Allergy 2003;33(9):1190-7.
  21.  Remes ST, Castro-Rodriguez JA, Holberg CJ, Martinez FD, Wright AL. Dog exposure in infancy decreases the subsequent risk of frequent wheeze but not of atopy. J Allergy Clin Immunol 2001;108:509-15.
  22. McConnell R, Berhane K, Gilliland F, Islam T, Gauderman WJ, London SJ, Avol E, Rappaport EB, Margolis HG, Peters JM. Indoor risk factors for asthma in a prospective study of adolescents. Epidemiology 2002;13:288-95.
  23. Almqvist C, Larsson PH, Egmar AC, Hedren M, Malmberg P, Wickman M. School as a risk environment for children allergic to cats and a site for transfer of cat allergen to homes. J Allergy Clin Immunol 1999;103:1012-7.
  24. Ritz BR, Hoelscher B, Frye C, Meyer I, Hemrich J. Allergic sensitization owing to 'second-hand' cat exposure in schools. Allergy 2002;57:357-61.
  25.  Phipatanakul W. Animal allergens and their control. Curr Allergy Asthma Rep 2001;1(5):461-5.
  26.  Schou C, Svendsen VG, Lowenstein H. Purification and characterization of the major dog allergen, Can f I. Clin Exp Allergy 1991;21:321-8.
  27. Boutin Y, Hebert H, Vrancken ER, Mourad W. Allergenicity and cross reactivity of cat and dog allergenic extracts. Clin Allergy 1988;18(3):287-93.
  28. Spitzauer S, Schweiger C, Sperr WR, Pandjaitan B, Valent P, Mühl S, Ebner C, Scheiner O, Kraft D, Rumpold H, et al. Molecular characterization of dog albumin as a cross-reactive allergen. J Allergy Clin Immunol 1994;93(3):614-27.
  29. Haahtela T, Jaakonmaki I. Relationship of allergen specific IgE antibodies, skin prick tests and allergic disorders in unselected adolescents. Allergy 1981;36:251-6.
  30. Schou C. Defining allergens of mammalian origin. Clin Exp Allergy 1993,23:7-14.
  31. Aoyama K, Ueda A, Manda F, Matsushita T, Ueda T, Yamauchi C. Allergy to laboratory animals: an epidemiological study. Br J Ind Med 1992;49(1):41-7.
  32. Konieczny A, Morgenstern JP, Bizinkauskas CB, Lilley CH, Brauer AW, Bond JF, Aalberse RC, Wallner BP, Kasaian MT. 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(4):577-86.
  33. Saarelainen S, Taivainen A, Rytkonen-Nissinen M, Auriola S, Immonen A, Mantyjarvi R, Rautiainen J, Kinnunen T, Virtanen T. Assessment of recombinant dog allergens Can f 1 and Can f 2 for the diagnosis of dog allergy. Clin Exp Allergy 2004;34(10):1576-82.
  34. Immonen A, Farci S, Taivainen A, Partanen J, Pouvelle-Moratille S, Narvanen A, Kinnunen T, Saarelainen S, Rytkonen-Nissinen M, Maillere B, Virtanen T. T cell epitope-containing peptides of the major dog allergen Can f 1 as candidates for allergen immunotherapy. J Immunol 2005;175(6):3614-20.
  35. International Union of Immunological Societies Allergen Nomenclature: IUIS official list http://www.allergen.org/. 2011.
  36.  Heutelbeck AR, Schulz T, Bergmann KC, Hallier E. Environmental exposure to allergens of different dog breeds and relevance in allergological diagnostics. J Toxicol Environ Health A 2008;71(11-12):751-8.
  37. Kamata Y, Miyanomae A, Nakayama E, Miyanomae T, Tajima T, Nishimura K, Tada T, Hoshi H. Characterization of dog allergens Can f 1 and Can f 2. 2. A comparison of Can f 1 with Can f 2 regarding their biochemical and immunological properties. Int Arch Allergy Immunol 2007;142(4):301-8.
  38. Pandjaitan B, Swoboda I, Brandejsky-Pichler F, Rumpold H, Valenta R, Spitzauer S. Escherichia coli expression and purification of recombinant dog albumin, a cross-reactive animal allergen. J Allergy Clin Immunol 2000;105(2 Pt 1):279-85.
  39. Mattsson L, Lundgren T, Olsson P, Sundberg M, Lidholm J. Molecular and immunological characterization of Can f 4: a dog dander allergen cross-reactive with a 23 kDa odorant-binding protein in cow dander. Clin Exp Allergy 2010;40(8):1276-87.
  40. Mattsson L, Lundgren T, Everberg H, Larsson H, Lidholm J. Prostatic kallikrein: A new major dog allergen. J Allergy Clin Immunol 2009;123(2):362-8.
  41. Chapdelaine P, Gauthier E, Ho-Kim MA, Bissonnette L, Tremblay RR, Dubé JY. Characterization and expression of the prostatic arginine esterase gene, a canine glandular kallikrein. DNA Cell Biol 1991;10(1):49-59.
  42.  Chapdelaine P, Ho-Kim MA, Tremblay RR, Dubé JY. Nucleotide sequence of the androgen-dependent arginine esterase mRNA of canine prostate. FEBS Lett 1988;232(1):187-92.
  43. Lazure C, Leduc R, Seidah NG, Chrétien M, Dubé JY, Chapdelaine P, Frenette G, Paquin R, Tremblay RR. The major androgen-dependent protease in dog prostate belongs to the kallikrein family: confirmation by partial amino acid sequencing. FEBS Lett 1984;175(1):1-7.
  44. Ichikawa K, Vailes LD, Pomes A, Chapman MD. Molecular cloning, expression and modelling of cat allergen, cystatin (Fel d 3), a cysteine protease inhibitor. Clin Exp Allergy 2001;31(8):1279-86.
  45. Spitzauer S, Schweiger C, Anrather J, Ebner C, Scheiner O, Kraft D, Rumpold H. Characterisation of dog allergens by means of immunoblotting. Int Arch Allergy Immunol 1993;100(1):60-7.
  46. Spitzauer S, Pandjaitan B, Muhl S, Ebner C, Kraft D, Valenta R, Rumpold H. Major cat and dog allergens share IgE epitopes. J Allergy Clin Immunol 1997;99(1 Pt 1):100-6.
  47. Reininger R, Varga EM, Zach M, Balic N, Lindemeier AD, Swoboda I, Grönlund H, van Hage M, Rumpold H, Valenta R, Spitzauer S. Detection of an allergen in dog dander that cross-reacts with the major cat allergen, Fel d 1. Clin Exp Allergy 2007;37(1):116-24.
  48. Niederberger V, Stubner P, Spitzauer S, Kraft D, Valenta R, Ehrenberger K, Horak F. Skin test results but not serology reflect immediate type respiratory sensitivity: a study performed with recombinant allergen molecules. J Invest Dermatol 2001;117(4):848-51.
  49. Kamata Y, Miyanomae A, Nakayama E, Miyanomae T, Tajima T, Hoshi H. Characterization of dog allergens Can f 1 and Can f 2. 1. Preparation of their recombinant proteins and antibodies. Int Arch Allergy Immunol 2007;142(4):291-300.
  50. Mantyjarvi R, Rautiainen J, Virtanen T. Lipocalins as allergens. Biochim Biophys Acta 2000;1482(1-2):308-17.
  51. Virtanen T, Zeiler T, Mäntyjärvi R. Important animal allergens are lipocalin proteins: why are they allergenic? Int Arch Allergy Immunol 1999;120:247-58.
  52. Larson JN, Ford A, Gjesing B, Levy D, Petrunov B, Silvestri L. The collaborative study of the international standard of dog, Canis Domesticus, hair/dander extract. J Allergy Clin Immunol 1988;82:318-25.
  53. Spitzauer S, Schweiger C, Anrather J, Ebner C, Scheiner O, Kraft D. Characterization of dog allergens by means of immunoblotting. Int Arch Allergy Immunol 1993;100:60-7.
  54. Van der Veen MJ, Mulder M, Witteman AM, van Ree R, Aalberse RC, Jansen HM, van der Zee JS. False-positive skin prick test responses to commercially available dog dander extracts caused by contamination with house dust mite (Dermatophagoides pteronyssinus) allergens. J Allergy Clin Immunol 1996;98(6 Pt 1):1028-34.
  55. Yman L, Brandt R, Ponterius G. Serum albumin--an important allergen in dog epithelia extracts. Int Arch Allergy Appl Immunol 1973;44(3):358-68.
  56. Goubran Botros H, Gregoire C, Rabillon J, David B, Dandeu JP. Cross-antigenicity of horse serum albumin with dog and cat albumins: study of three short peptides with significant inhibitory activity towards specific human IgE and IgG antibodies. Immunology 1996;88(3):340-7.
  57. Blanc A, Donnay C, Metz-Favre C, de Blay F, Pauli G. Sensibilisation concomitante au chat et au chien : cosensibilisation ou allergènes croisants ? / Concomitant sensitization to cat and dog: Cosensitization or cross-reacting allergens? Revue Francaise D Allergologie 2007;47(5):375-6.
  58. McLean AC, Glovsky MM, Hoffman DR, Ghekiere LM. Identification of allergens in dog dander extract. I. Clinical and immunological aspects of allergenicity activity. Ann Allergy 1980;45(4):199-204.
  59. Vanto T, Viander M, Schwartz B. Dog serum albumin as an allergen. IgE, IgG and lymphocyte responses in dog dander-sensitive asthmatic children. Int Arch Allergy Appl Immunol 1982;69(4):311-5.
  60. Cabañas R, López-Serrano MC, Carreira J, Ventas P, Polo F, Caballero MT, Contreras J, Barranco P, Moreno-Ancillo A. Importance of albumin in cross-reactivity among cat, dog and horse allergens. J Investig Allergol Clin Immunol 2000;10(2):71-7.
  61. Spitzauer S, Pandjaitan B, Söregi G, Mühl S, Ebner C, Kraft D, Valenta R, Rumpold H. IgE cross-reactivities against albumins in patients allergic to animals. J Allergy Clin Immunol 1995;96(6 Pt 1):951-9.
  62. San-Juan S, Lezaun A, Caballero ML, Moneo I. Occupational allergy to raw beef due to cross-reactivity with dog epithelium. Allergy 2005;60(6):839-40.
  63. Vicente-Serrano J, Caballero ML, Rodriguez-Perez R, Carretero P, Perez R, Blanco JG, Juste S, Moneo I. Sensitization to serum albumins in children allergic to cow's milk and epithelia. Pediatr Allergy Immunol 2007;18(6):503-7.
  64. Donnay C, Barderas R, Kopferschmitt-Kubler MC, Pauli G, Blay F. Sensitization to pig albumin and gamma-globulin responsible for occupational respiratory allergy 2006;61(1):143-4.
  65.  Drouet M, Boutet S, Lauret MG, Chène J, Bonneau JC, Le Sellin J, Hassoun S, Gay G, Sabbah A. The pork-cat syndrome or crossed allergy between pork meat and cat epithelia (1) [French]. Allerg Immunol (Paris) 1994;26(5):166-8,171-2.
  66. Chapdelaine P, Potvin C, Ho-Kim MA, Larouche L, Bellemare G, Tremblay RT, Dubé JY. Androgen regulation of canine prostatic arginine esterase mRNA using cloned cDNA. Mol Cell Endocrinol 1988;56(1-2):63-70.
  67. Basagana M, Bartolome B, Pastor C, Torres F, Alonso R, Vivanco F, Cistero-Bahima A. Allergy to human seminal fluid: cross-reactivity with dog dander. J Allergy Clin Immunol 2008;121(1):233-9.
  68. Weidinger S, Mayerhofer A, Raemsch R, Ring J, Kohn FM. Prostate-specific antigen as allergen in human seminal plasma allergy. J Allergy Clin Immunol 2006;117(1):213-5.

 

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