clear search
Search
Recent searches Clear History
Fale conosco
Allergen Encyclopedia
Table of Contents

Alérgeno completo

e5 Dog dander

e5 Dog dander Scientific Information

Tipo:

Whole Allergen

Nome para exibição:

Dog dander

Route of Exposure:

Inhalation

Family:

Canidae

Species:

C.lupus

Latin Name:

Canis familiaris

Other Names:

Domestic Dog, Hound

Summary

Dogs have a global distribution and all dogs produce allergens. Allergic sensitization to dogs is considered to be a risk factor for asthma and rhinitis, and has increased significantly over recent decades for both children and adults. Dog allergen particles are tiny so they easily become airborne, disperse effectively, and can enter small bronchioles to reach lower airways. Dog hair and dander extracts contain many antigens, any of which can bind to IgE antibodies and trigger respiratory symptoms in sensitized individuals. Many of these compounds also cross-react with other mammalian allergens, which poses extended diagnostic and therapeutic challenges. Evaluating dog sensitization can be challenging, but the introduction of molecular-based diagnostics has been an important step forwards in the accurate diagnosis of dog allergy.

 

Allergen

Taxonomy

Canis familiaris is a sub-species of Canis lupus (family Canidae of the order Carnivora), and commonly known as dog or domestic dog (1).

Taxonomic tree of Dog 
Domain Eukaryota
Kingdom Animalia
Phylum Chordata
Subphylum Vertebrata
Class Mammalia
Order Carnivora
Family Canidae
Genus Canis
Species C. familiaris

 

Epidemiology

Worldwide distribution

A 2016 survey of more than 27,000 internet users from 22 countries reported that one-third (33%) of people have a dog living in their home (2). Allergy to dogs has been recognized for many years (3), but the prevalence of dog sensitization varies geographically due to cultural differences, environmental factors and pet ownership (4). In a large pan-European study of adults referred to allergy testing clinics, approximately 27% (range, 16.1–56.0%) were sensitized to dogs (5). In Korea, 20.4% of adults assessed for various allergic diseases were sensitized to dogs, and direct exposure to dogs was an independent risk factor for sensitization to dog allergens (6).

Allergic sensitization to dog dander was reported by nearly one in ten (9.7%) German children aged 3–17 years (7), and the prevalence of sensitization increased with the age of the child (7, 8). Two large population-based surveys have demonstrated how sensitization to dog allergens has increased significantly over time for both children (Brazil: 8.1% in 2004 to 40.3% in 2016; p<0.001) (9) and adults (Sweden: 13% in 1994 to 25% in 2009; p<0.001) (10), which may be due to the hygiene hypothesis, changes in the manufacturing of agricultural products, and increased urban living with sedentary indoor lifestyle behaviors (9, 10). Of note, adults are more likely than children to be mono-sensitized to animal allergen components (11, 12).

These recent surges in sensitization are of concern because allergic sensitization to dogs may be a risk factor for asthma and rhinitis (3, 9, 13). Regardless of dog ownership, a Japanese study reported that more children with asthma were sensitized to dog allergens before they developed respiratory symptoms than non-asthma children (13).

Environmental Characteristics

Worldwide distribution

Dogs have a global distribution and an estimated total population size of 700 million (14). Dogs have evolved a close relationship with humans and can be found as owned pets in households or as free-roaming strays in urban and rural environments (14). Concentrations of dog allergens are highest in indoor environments where these animals are kept, but can also be detected in other indoor or public places where dogs have never been kept because of passive transfer (3, 4).

Living environment

Dogs release allergens through secretions and on tiny particles of skin scales (dander) between 2–5 microns in size (1 micron = 1/25,000 inch) which are commonly found in household dust (4, 15, 16). These particles easily become airborne under normal ventilation so can disperse effectively, and their tiny size enables them to enter small bronchioles and reach lower airways to trigger respiratory symptoms in sensitized individuals (3, 4, 16, 17). Dog hair and dander extracts are complex mixtures of components with more than 28 antigens, any of which can bind to IgE antibodies with varying frequency and intensity in dog-sensitive patients (18).

All dogs produce allergens, however, there are differences between breeds and between individuals within breeds (17, 19-21). Certain breeds are more susceptible to eczema and oily seborrhea, while older dogs have drier skin and produce more dander than younger dogs (22). Seasonal variation can also affect the levels of dog IgE antibodies (22).

All homes with dogs have high levels of dog allergens (23, 24). In private homes, dog allergens have been measured at 1 to >10 micrograms per gram of dust (4, 16), and airborne Can f 1 can range from 0.3 to 99 nanograms per cubic meter of air (16). Levels in homes without dogs maybe 10–100 times lower, but are still detectable and can affect sensitized individuals (4, 16, 23, 24). The threshold level for sensitization to Can f 1 is >2 micrograms per gram, while the threshold level associated with asthma symptoms in sensitized individuals is >10 micrograms per gram (25). 

In both homes with and without pets, the highest levels of pet allergens in dust reservoirs and air are found in the living room and bedroom (16, 23, 24). Carpets and upholstery are major reservoirs for dog allergens, however, detectable levels are also present on bare floors and smooth surfaces such as walls and furniture (16, 26).

School

Apart from the home, school is the most important indoor environment for children (25, 27). Many studies have detected dog allergens in schools at levels exceeding those needed to induce sensitization (27-30). However, levels of dog allergens can vary extensively both within and between schools, depending on factors including the presence of open shelving with settled dust, the extent of carpeted or upholstered areas, and the number of pet owners visiting the school (4, 25, 27, 29).

Classroom fittings, particularly chairs, can act as both direct and indirect sources of different particles and compounds, and the concentration of animal dander allergens in school dust frequently exceeds the amount measured in homes with no furred pets (25, 27, 28, 30). This means that children with asthma and other allergic diseases can be exposed to dog allergens at school even if they have no dogs at home (29, 30). The main source of animal allergens brought into the school setting is the clothing of pet owners (31). It is possible to reduce the levels of animal allergens if students change into school uniforms which are stored and washed at school (31). A Swedish national position paper on asthma and allergies at school recommended that furred animals including dogs should not be allowed on school premises at any time, in order to decrease the allergen levels in favor of pet allergic pupils (32).

Other topics

Significant exposure to domestic allergens can occur outside homes (33). The particles that carry dog allergens are sticky (3), and passive transfer on clothing or human hair can easily transport them to places such as schools, offices, hospitals, automobiles, public transport, and other places where dogs are not usually present (25, 29, 34-36). In these areas, furnishings, textiles such as curtains, upholstery and dust can act as significant reservoirs of allergens and impact indoor air quality (27, 33, 35, 36) in levels which may be higher than those in homes without a dog (34). While levels of allergens may be relatively low in environments outside the home, this exposure could be important for sensitized individuals who do not have a pet at home (29, 35, 36).

For example, upholstered chairs in hospitals constitute a significant reservoir of dog allergen particles, which if inhaled by patients attending appointments could exacerbate asthma (33). Additionally, a public transport study in Helsinki found just over half (53%) of passengers with allergy or asthma had been inconvenienced by symptoms during travel, even though only 0.13% of passengers travelled with a pet (36). 

Detection

Environmental source

The dog allergens (Canis familiaris allergens, e.g. Can f 1, Can f 2, Can f 4, and Can f 6) are ubiquitous and found in dog hair, dander and saliva, (3, 53). Can f 3 is also present in serum and Can f 5 in non-neutered male urine (17).

Can f 1 levels are not affected by the number of dogs in the home, but are significantly related to the amount of time a dog is kept indoors (54). Dog gender and breed may affect shedding of allergens and endotoxins into the environment (49). For instance, Can f 5 is only present in significant quantities in intact male dogs (17), which may help explain why children exposed to female dogs have a lower risk of asthma compared to those exposed to male dogs (49). While certain breeds may be marketed as “hypoallergenic” due to reduced shedding or a compact coat, two separate studies failed to show any difference in allergen shedding between dog breed groups (50, 51). 

Clinical Relevance

Asthma and allergic rhinitis

Sensitization to dog allergen in early life is a strong predictor of the development of childhood asthma (37). Furthermore, the probability of remission of childhood asthma in later adolescence is reduced if the individual is sensitized to furry animals such as dogs (38). Contact with an allergen source can cause not only immediate symptoms but also a prolonged period of bronchial hyperreactivity which can last for several weeks (28).

In the UK, dog-sensitized children aged three years who were exposed to high levels of dog allergen had significantly poorer lung function compared to sensitized children who were not exposed (p=0.005) (39). A large population-based survey in the US similarly reported an increased prevalence of asthma and emergency care visits among dog-sensitized individuals exposed to elevated levels of allergens, and attributed 44.2% of asthma attacks to high levels of dog allergen in the bedroom (37). Projection of these results to the entire US population indicated more than one million increased asthma attacks per year for dog-sensitive and exposed individuals (37).

Other topics

Interestingly, approximately half (51%) of patients with severe asthma in Germany, who were previously considered nonatopic on the basis of non-standardized allergy testing, demonstrated allergic sensitization when tested against an extended panel of aeroallergens including dog dander (40).

Diagnostics Sensitization

Skin prick tests

Diagnosis of dog allergy can be difficult: many patients are misclassified due to self-reporting and even structured allergy history assessments can produce high levels (i.e. 27%) of false-positive rates for dog allergy (41). Serum IgE to dog epithelium has a poor correlation to skin testing with only 52.2% agreement and a correlation coefficient r=0.37 (42). Academic studies utilizing component resolved diagnostics have reported only 64% of sensitized adults have IgE reactive to Can f 1, while only one-third (32%) of those individuals are mono-sensitized to Can f 1 (22, 43). This suggests clinicians relying on these tests may be falsely assuming these patients are not dog-sensitized (22).

Evaluating dog sensitization is significantly more challenging and complex than it is for cats, and there remains a great difficulty in using skin prick tests (SPT) for detecting dog-allergic patients (22). Commercially-available dog extracts used in skin testing are composed of multiple proteins which vary by up to 1,000-fold in potency (22). The amounts of identified allergens in each extract are unclear as crude dog extracts are not standardized, and considerable variation in SPT results can also depend on the source of the extract used (e.g. liver, serum, salivary gland or keratinocyte) (20, 22, 44). This extensive variation in the allergen composition of commercial SPT solutions results in a patient-dependent ability to activate basophils (20). Contamination of the extract by non-dog allergens can cause false positives during testing, which also severely limits the utility of crude dog extracts in SPT to accurately identify sensitized individuals (22). 

Prevention and Therapy

Prevention strategies

The effect of dog ownership on the development of asthma is inconclusive. Overall, dog ownership at an early age has either been demonstrated to reduce the risk of asthma at a later age (45), or increase the risk of asthma and wheezing (e.g. systematic reviews by (46) and (47)). However, ownership of two or more dogs during the first year of life has been specifically associated with reduced risks of atopy, seroatopy and asthma in children by the time they reached six or seven years of age, versus children who were exposed to no dogs or just one dog (48, 49). The true picture of the relationship between risk and dog ownership is complicated by differences in study design and selection bias, as well as age-related heterogeneity (46, 47).

While certain breeds may be marketed as “hypoallergenic” due to reduced shedding or a compact coat, studies have failed to show any difference in allergen shedding between dog breed groups (50, 51). Washing a dog at least twice a week significantly reduces recoverable Can f 1 in hair and dander samples, and moderately reduces airborne Can f 1 (52). Effective cleaning of floors and seats, as well as the use of uncovered versus covered seats, has been shown to lower the levels of animal allergens in public environments (26, 27, 33, 34, 36).

Molecular Aspects

Allergenic molecules

Main Allergen  Component Function 
Dog Dander Can f 1 Lipocalin
Can f 2 Lipocalin
Can f 3 Serum Albumin
Can f 4 Lipocalin
Can f 5 Arginine esterase, prostatic kallikrein
Can f 6 Lipocalin
Can f 7 Epididymal Secretory Protein E1, or Nielmann Pick type C2 protein

Four of the seven currently-identified dog allergens are lipocalins (Can f 1, Can f 2, Can f 4 and Can f 6) (3). Approximately half of dog-allergic individuals have IgE directly exclusively to Can f 1 (55, 56), and between 20–33% have IgE antibodies to Can f 2 (3). All dog-sensitized patients with reactivity to Can f 2 also react to Can f 1 (3, 57). However, the overall IgE reactivity of natural Can f 4 depends strongly on the integrity of the allergen’s physical conformation, with various studies reporting between 30% to over 80% of dog-sensitized subjects reacting to Can f 4 (3, 58). Can f 6 is considered a major dog dander allergen for both children and adults (59-61), and a key lipocalin driving disease among dog-allergic individuals (62, 63).

Can f 3 is a serum albumin protein which is very common in house dust (15), and important for up to 35% of patients allergic to dogs (64). Can f 5 is a prostatic kallikrein produced by male dogs (43, 65), and the most common dog component to cause sensitization in adults (11) and children (66). In two separate studies of dog-allergic adults, approximately 70% demonstrated IgE reactivity to Can f 5 while just over one-third (37%) reacted to Can f 5 alone (65, 67). Mono-sensitization to Can f 5 suggests that some dog-allergic individuals react specifically to male, not female, dogs (65, 68, 69).

Cross-reactivity

Co-sensitization between dog, cat and horse is frequently observed (3). Cross-reactivity between Can f 1 and Fel d 7 (a lipocalin allergy found in cats) is likely as the proteins share 62% sequence identity (3). Can f 2 has homology with the allergen mouse urinary protein (MUP) (55), but shows limited patient-dependent cross-reactivity (22%) with Fel d 4 (3). Can f 4 displays 38% sequence identity to bovine and porcine odorant-binding proteins, and between 25–29% identity to several known mammalian allergens including Equ c 1, Mus m 1, Rat n 1, and Fel d 4 (70). Despite belonging to the same lipocalin protein family, Can f 4 shows only about 25% sequence identity to Can f 1 and Can f 2 (70). Can f 6 has shown extensive cross-reactivity with both horse and cat lipocalins (59, 63) and may contribute with these homologous allergens to multi-sensitization and symptoms in individuals allergic to mammals (61).

Mono-sensitization to Can f 3 appears to be very rare (71), and this albumin has high sequence homology with albumins from many other mammals including human, pig, cattle, cat, sheep, mouse and rat (64, 72, 73). Can f 5 cross-reacts with prostate-specific antigen (PSA) of human seminal plasma (HSP), which can be significant for patients with anaphylactic HSP allergies (74-77). 

Compiled By

Author: RubyDuke Communications

Reviewer: Dr. Magnus Borres

 

Last reviewed: December 2020

 

References
  1. ITIS. Canis lupus familiaris Linnaeus 1758 2020 [cited 2020 November]. Available from: https://www.itis.gov/servlet/SingleRpt/SingleRpt?search_topic=TSN&search_value=726821#null.
  2. Knowledge Gf. Man's best friend: global pet ownership and feeding trends 2016 [cited 2020 November]. Available from: https://www.gfk.com/insights/mans-best-friend-global-pet-ownership-and-feeding-trends.
  3. Konradsen JR, Fujisawa T, van Hage M, Hedlin G, Hilger C, Kleine-Tebbe J, et al. Allergy to furry animals: New insights, diagnostic approaches, and challenges. J Allergy Clin Immunol. 2015;135(3):616-25.
  4. Liccardi G, Triggiani M, Piccolo A, Salzillo A, Parente R, Manzi F, et al. Sensitization to Common and Uncommon Pets or Other Furry Animals: Which May Be Common Mechanisms? Transl Med UniSa. 2016;14:9-14.
  5. Heinzerling LM, Burbach GJ, Edenharter G, Bachert C, Bindslev-Jensen C, Bonini S, et al. GA(2)LEN skin test study I: GA(2)LEN harmonization of skin prick testing: novel sensitization patterns for inhalant allergens in Europe. Allergy. 2009;64(10):1498-506.
  6. Park YB, Mo EK, Lee JY, Kim JH, Kim CH, Hyun IG, et al. Association between pet ownership and the sensitization to pet allergens in adults with various allergic diseases. Allergy Asthma Immunol Res. 2013;5(5):295-300.
  7. Schmitz R, Ellert U, Kalcklösch M, Dahm S, Thamm M. Patterns of sensitization to inhalant and food allergens - findings from the German Health Interview and Examination Survey for Children and Adolescents. Int Arch Allergy Immunol. 2013;162(3):263-70.
  8. Wickman M, Asarnoj A, Tillander H, Andersson N, Bergström A, Kull I, et al. Childhood-to-adolescence evolution of IgE antibodies to pollens and plant foods in the BAMSE cohort. J Allergy Clin Immunol. 2014;133(2):580-2.
  9. Aranda CS, Cocco RR, Pierotti FF, Mallozi MC, Franco JM, Porto A, et al. Increased sensitization to several allergens over a 12-year period in Brazilian children. Pediatr Allergy Immunol. 2018;29(3):321-4.
  10. Warm K, Lindberg A, Lundbäck B, Rönmark E. Increase in sensitization to common airborne allergens among adults - two population-based studies 15 years apart. Allergy Asthma Clin Immunol. 2013;9(1):20.
  11. Suzuki S, Nwaru BI, Ekerljung L, Sjölander S, Mincheva R, Rönmark EP, et al. Characterization of sensitization to furry animal allergen components in an adult population. Clin Exp Allergy. 2019;49(4):495-505.
  12. Bjerg A, Winberg A, Berthold M, Mattsson L, Borres MP, Rönmark E. A population-based study of animal component sensitization, asthma, and rhinitis in schoolchildren. Pediatr Allergy Immunol. 2015;26(6):557-63.
  13. Nagao M, Borres MP, Sugimoto M, Petersson CJ, Nakayama S, Kuwabara Y, et al. Sensitization to secretoglobin and lipocalins in a group of young children with risk of developing respiratory allergy. Clin Mol Allergy. 2017;15:4.
  14. Smith LM, Hartmann S, Munteanu AM, Dalla Villa P, Quinnell RJ, Collins LM. The Effectiveness of Dog Population Management: A Systematic Review. Animals (Basel). 2019;9(12).
  15. 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.
  16. Custovic A, Green R, Fletcher A, Smith A, Pickering CA, Chapman MD, et al. Aerodynamic properties of the major dog allergen Can f 1: distribution in homes, concentration, and particle size of allergen in the air. Am J Respir Crit Care Med. 1997;155(1):94-8.
  17. Dávila I, Domínguez-Ortega J, Navarro-Pulido A, Alonso A, Antolín-Amerigo D, González-Mancebo E, et al. Consensus document on dog and cat allergy. Allergy. 2018;73(6):1206-22.
  18. Ford AW, Alterman L, Kemeny DM. The allergens of dog. I. Identification using crossed radio-immunoelectrophoresis. Clin Exp Allergy. 1989;19(2):183-90.
  19. de Groot H, Goei KG, 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(6):1056-65.
  20. Wintersand A, Asplund K, Binnmyr J, Holmgren E, Nilsson OB, Gafvelin G, et al. Allergens in dog extracts: Implication for diagnosis and treatment. Allergy. 2019;74(8):1472-9.
  21. Calam DH, Davidson J, Ford AW. Studies on allergens of mammalian origin. J Chromatogr. 1984;288(1):137-45.
  22. Chan SK, Leung DYM. Dog and Cat Allergies: Current State of Diagnostic Approaches and Challenges. Allergy Asthma Immunol Res. 2018;10(2):97-105.
  23. 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.
  24. Custis NJ, Woodfolk JA, Vaughan JW, Platts-Mills TA. Quantitative measurement of airborne allergens from dust mites, dogs, and cats using an ion-charging device. Clin Exp Allergy. 2003;33(7):986-91.
  25. Esty B, Permaul P, DeLoreto K, Baxi SN, Phipatanakul W. Asthma and Allergies in the School Environment. Clin Rev Allergy Immunol. 2019;57(3):415-26.
  26. 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.
  27. Smedje G, Norbäck D. Irritants and allergens at school in relation to furnishings and cleaning. Indoor Air. 2001;11(2):127-33.
  28. Munir AK, Einarsson R, Schou C, Dreborg SK. Allergens in school dust. I. The amount of the major cat (Fel d I) and dog (Can f I) allergens in dust from Swedish schools is high enough to probably cause perennial symptoms in most children with asthma who are sensitized to cat and dog. J Allergy Clin Immunol. 1993;91(5):1067-74.
  29. Berge M, Munir AK, Dreborg S. Concentrations of cat (Fel d1), dog (Can f1) and mite (Der f1 and Der p1) allergens in the clothing and school environment of Swedish schoolchildren with and without pets at home. Pediatr Allergy Immunol. 1998;9(1):25-30.
  30. Lönnkvist K, Halldén G, Dahlén SE, Enander I, van Hage-Hamsten M, Kumlin M, et al. 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.
  31. Karlsson AS, Andersson B, Renström A, Svedmyr J, Larsson K, Borres MP. Airborne cat allergen reduction in classrooms that use special school clothing or ban pet ownership. J Allergy Clin Immunol. 2004;113(6):1172-7.
  32. Borres MP, Abrahamsson G, Andersson B, Andersson B, Bråkenhielm G, Fabricius T, et al. Asthma and allergies at school--a Swedish national position paper. Allergy. 2002;57(5):454-7.
  33. Custovic A, Fletcher A, Pickering CA, Francis HC, Green R, Smith A, et al. 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.
  34. Custovic A, Green R, Taggart SC, Smith A, Pickering CA, Chapman MD, et al. Domestic allergens in public places. II: Dog (Can f1) and cockroach (Bla g 2) allergens in dust and mite, cat, dog and cockroach allergens in the air in public buildings. Clin Exp Allergy. 1996;26(11):1246-52.
  35. 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.
  36. Partti-Pellinen K, Marttila O, Mäkinen-Kiljunen S, Haahtela T. Occurrence of dog, cat, and mite allergens in public transport vehicles. Allergy. 2000;55(1):65-8.
  37. Gergen PJ, Mitchell HE, Calatroni A, Sever ML, Cohn RD, Salo PM, et al. Sensitization and Exposure to Pets: The Effect on Asthma Morbidity in the US Population. J Allergy Clin Immunol Pract. 2018;6(1):101-7.e2.
  38. Andersson M, Hedman L, Bjerg A, Forsberg B, Lundbäck B, Rönmark E. Remission and persistence of asthma followed from 7 to 19 years of age. Pediatrics. 2013;132(2):e435-42.
  39. Lowe LA, Woodcock A, Murray CS, Morris J, Simpson A, Custovic A. Lung function at age 3 years: effect of pet ownership and exposure to indoor allergens. Arch Pediatr Adolesc Med. 2004;158(10):996-1001.
  40. Schreiber J, Bröker BM, Ehmann R, Bachert C. Nonatopic severe asthma might still be atopic: Sensitization toward Staphylococcus aureus enterotoxins. J Allergy Clin Immunol. 2019;143(6):2279-80.e2.
  41. Gerth van Wijk R. Diagnosis of dog allergy: Beware of the dog. J Allergy Clin Immunol. 2018;142(4):1058-9.
  42. Chinoy B, Yee E, Bahna SL. Skin testing versus radioallergosorbent testing for indoor allergens. Clin Mol Allergy. 2005;3(1):4.
  43. Ukleja-Sokołowska N, Gawrońska-Ukleja E, Żbikowska-Gotz M, Socha E, Lis K, Sokołowski Ł, et al. Analysis of feline and canine allergen components in patients sensitized to pets. Allergy Asthma Clin Immunol. 2016;12:61.
  44. Curin M, Reininger R, Swoboda I, Focke M, Valenta R, Spitzauer S. Skin prick test extracts for dog allergy diagnosis show considerable variations regarding the content of major and minor dog allergens. Int Arch Allergy Immunol. 2011;154(3):258-63.
  45. Fall T, Lundholm C, Örtqvist AK, Fall K, Fang F, Hedhammar Å, et al. Early Exposure to Dogs and Farm Animals and the Risk of Childhood Asthma. JAMA Pediatr. 2015;169(11):e153219.
  46. Apelberg BJ, Aoki Y, Jaakkola JJ. Systematic review: Exposure to pets and risk of asthma and asthma-like symptoms. J Allergy Clin Immunol. 2001;107(3):455-60.
  47. Takkouche B, González-Barcala FJ, Etminan M, Fitzgerald M. Exposure to furry pets and the risk of asthma and allergic rhinitis: a meta-analysis. Allergy. 2008;63(7):857-64.
  48. 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(8):963-72.
  49. Fall T, Ekberg S, Lundholm C, Fang F, Almqvist C. Dog characteristics and future risk of asthma in children growing up with dogs. Sci Rep. 2018;8(1):16899.
  50. Vredegoor DW, Willemse T, Chapman MD, Heederik DJ, Krop EJ. Can f 1 levels in hair and homes of different dog breeds: lack of evidence to describe any dog breed as hypoallergenic. J Allergy Clin Immunol. 2012;130(4):904-9.e7.
  51. Nicholas CE, Wegienka GR, Havstad SL, Zoratti EM, Ownby DR, Johnson CC. Dog allergen levels in homes with hypoallergenic compared with nonhypoallergenic dogs. Am J Rhinol Allergy. 2011;25(4):252-6.
  52. Hodson T, Custovic A, Simpson A, Chapman M, Woodcock A, Green R. Washing the dog reduces dog allergen levels, but the dog needs to be washed twice a week. J Allergy Clin Immunol. 1999;103(4):581-5.
  53. Hilger C, Swiontek K, Arumugam K, Lehners C, Hentges F. Identification of a new major dog allergen highly cross-reactive with Fel d 4 in a population of cat- and dog-sensitized patients. J Allergy Clin Immunol. 2012;129(4):1149-51.
  54. Nicholas C, Wegienka G, Havstad S, Zoratti E, Ownby D, Johnson CC. Dog characteristics and allergen levels in the home. Ann Allergy Asthma Immunol. 2010;105(3):228-33.
  55. Konieczny A, Morgenstern JP, Bizinkauskas CB, Lilley CH, Brauer AW, Bond JF, 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(4):577-86.
  56. Schou C, Svendsen UG, Løwenstein H. Purification and characterization of the major dog allergen, Can f I. Clin Exp Allergy. 1991;21(3):321-8.
  57. Saarelainen S, Taivainen A, Rytkönen-Nissinen M, Auriola S, Immonen A, Mäntyjärvi R, 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(10):1576-82.
  58. Rytkönen-Nissinen M, Saarelainen S, Randell J, Häyrinen J, Kalkkinen N, Virtanen T. IgE Reactivity of the Dog Lipocalin Allergen Can f 4 and the Development of a Sandwich ELISA for Its Quantification. Allergy Asthma Immunol Res. 2015;7(4):384-92.
  59. Hilger C, Kuehn A, Hentges F. Animal lipocalin allergens. Curr Allergy Asthma Rep. 2012;12(5):438-47.
  60. Wang YJ, Li L, Song WJ, Zhou YJ, Cao MD, Zuo XR, et al. Canis familiaris allergen Can f 6: expression, purification and analysis of B-cell epitopes in Chinese dog allergic children. Oncotarget. 2017;8(53):90796-807.
  61. Nilsson OB, Binnmyr J, Zoltowska A, Saarne T, van Hage M, Grönlund H. Characterization of the dog lipocalin allergen Can f 6: the role in cross-reactivity with cat and horse. Allergy. 2012;67(6):751-7.
  62. Clayton GM, White J, Lee S, Kappler JW, Chan SK. Structural characteristics of lipocalin allergens: Crystal structure of the immunogenic dog allergen Can f 6. PLoS One. 2019;14(9):e0213052.
  63. Käck U, Asarnoj A, Grönlund H, Borres MP, van Hage M, Lilja G, et al. Molecular allergy diagnostics refine characterization of children sensitized to dog dander. J Allergy Clin Immunol. 2018;142(4):1113-20.e9.
  64. Spitzauer S, Schweiger C, Sperr WR, Pandjaitan B, Valent P, Mühl S, et al. Molecular characterization of dog albumin as a cross-reactive allergen. J Allergy Clin Immunol. 1994;93(3):614-27.
  65. 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.
  66. Asarnoj A, Hamsten C, Wadén K, Lupinek C, Andersson N, Kull I, et al. Sensitization to cat and dog allergen molecules in childhood and prediction of symptoms of cat and dog allergy in adolescence: A BAMSE/MeDALL study. J Allergy Clin Immunol. 2016;137(3):813-21.e7.
  67. Basagaña M, Luengo O, Labrador M, Garriga T, Mattsson L, Lidholm J, et al. Component-Resolved Diagnosis of Dog Allergy. J Investig Allergol Clin Immunol. 2017;27(3):185-7.
  68. Konradsen JR, Nordlund B, Onell A, Borres MP, Grönlund H, Hedlin G. Severe childhood asthma and allergy to furry animals: refined assessment using molecular-based allergy diagnostics. Pediatr Allergy Immunol. 2014;25(2):187-92.
  69. Schoos AM, Bønnelykke K, Chawes BL, Stokholm J, Bisgaard H, Kristensen B. Precision allergy: Separate allergies to male and female dogs. J Allergy Clin Immunol Pract. 2017;5(6):1754-6.
  70. 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.
  71. Hilger C, van Hage M, Kuehn A. Diagnosis of Allergy to Mammals and Fish: Cross-Reactive vs. Specific Markers. Curr Allergy Asthma Rep. 2017;17(9):64.
  72. Spitzauer S, Pandjaitan B, Söregi G, Mühl S, Ebner C, Kraft D, et al. IgE cross-reactivities against albumins in patients allergic to animals. J Allergy Clin Immunol. 1995;96(6 Pt 1):951-9.
  73. 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.
  74. Basagaña M, Bartolomé B, Pastor C, Torres F, Alonso R, Vivanco F, et al. Allergy to human seminal fluid: cross-reactivity with dog dander. J Allergy Clin Immunol. 2008;121(1):233-9.
  75. Basagaña M, Bartolome B, Pastor-Vargas C, Mattsson L, Lidholm J, Labrador-Horrillo M. Involvement of Can f 5 in a case of human seminal plasma allergy. Int Arch Allergy Immunol. 2012;159(2):143-6.
  76. Kofler L, Kofler H, Mattsson L, Lidholm J. A case of dog-related human seminal plasma allergy. Eur Ann Allergy Clin Immunol. 2012;44(2):89-92.
  77. Tanaka M, Nakagawa Y, Kotobuki Y, Katayama I. A case of human seminal plasma allergy sensitized with dog prostatic kallikrein, Can f 5. Allergol Int. 2019;68(2):259-60.