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Dog dander

e226 Can f 5

Allergen Component
Biological Function Kallikrein
Code e226
Allergome Code 5762
Route of Exposure Inhalation
Source Material Dog Dander
Latin Name Canis familiaris
Categories Epidermal and Animal Proteins
Molecular Weight 28 kDa

Summary

Canis familiaris allergen 5 (Can f 5) is a prostatic kallikrein component of dog hair and dander which is produced by intact male dogs. Approximately two-thirds (70%) of dog-allergic individuals demonstrate IgE reactivity to Can f 5, while a substantial proportion of individuals are mono-sensitized to Can f 5 and react specifically to intact male dogs rather than female dogs or castrated male dogs. Sensitization to Can f 5 is associated with asthma and rhinoconjunctivitis symptoms, and can contribute to poly-sensitization in individuals with IgE responses to multiple animal allergen molecules. Due to cross-reactivity with prostate-specific antigen of human seminal plasma, sensitization to Can f 5 can cause sexual disorders such as infertility, or symptoms which may be significant for those patients with anaphylactic allergies.

Epidemiology

Worldwide distribution

Can f 5 is a major dog allergen, both in terms of frequency and magnitude of IgE antibody binding (1, 2). Can f 5 was the most common dog component to cause sensitization in a large study of Swedish adults (3). Another large population-based study showed that Can f 5 was the most frequently-recognized dog allergen across all age groups of children with cat and dog allergies, even though only about one in 10 of these individuals reported symptoms to dogs (4).

In two separate studies of dog-allergic adults, approximately 70% demonstrated IgE reactivity to Can f 5 while just over one-third (37–38%) reacted to Can f 5 alone (1, 5). Other studies have reported lower sensitization rates (31–52%), but similarly high proportions of patients mono-sensitized to Can f 5 (6-8).

Mono-sensitization to Can f 5 suggests that some dog-allergic individuals react specifically to male, not female, dogs (1, 9, 10). Children mono-sensitized to Can f 5 in a randomized clinical trial reacted differently to male and female dog extract provocation, suggesting tolerance to female dogs (11). Of note, Liccardi et al. considered that mono-sensitization to Can f 5 was a relatively “lucky” event (as opposed to mono-sensitization to other dog allergen components) as sensitized individuals might find they are able to tolerate a female or castrated male dog as a pet (12). Additionally, these individuals would be less likely to come into contact with Can f 5 allergen in public places, with consequent effects on their health (12).

Environmental Characteristics

Source and tissue

Can f 5 is produced in the prostate gland and present in male dog urine, hair and dander extracts (1, 4, 7). 

Clinical Relevance

Disease severity

IgE to Can f 5 may be more prominent for allergic airway disease in general than for dog allergy in particular (4). Mono-sensitization to Can f 5 has been strongly associated with rhinoconjunctivitis symptoms in children (2, 6, 8). Sensitization to Can f 5 has also been highlighted among children with severe asthma who, compared to children with controlled asthma, had an IgE response to more than three animal-derived allergen molecules including Can f 5 (2, 9, 13).

An epidemiological study in Sweden found lower risks of asthma in children exposed to female versus male dogs (14). This study also noted similar risks of asthma in children exposed to male dogs versus children not exposed to any dogs, indicating that ownership of a male dog is not associated with increased risk of asthma compared to children without dogs (14).

Other Topics

There is no cross-reactivity between Can f 5 and the dog allergen components Can f 1, Can f 2 or Can f 3 (1). 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 (15-18). The presence of sexual disorders (e.g. HSP allergy or infertility) was significantly more frequent among dog-allergic adults with IgE reactivity to Can f 5 compared to subjects who did not recognize Can f 5 (p<0.0107) (15). Similarly, a significant percentage of women with a male dog at home who were sensitized to Can f 5 reported intercourse symptoms (7/27, 26%) (19).

Molecular Aspects

Allergenic Molecules

Can f 5 is a prostatic kallikrein that is present in male dog urine, hair and dander extracts (1, 4). Can f 5 has a molecular weight of 28 kDa (16). 

Cross-reactivity

Can f 5 shares structural similarity with human prostate-specific antigen (PSA), and an intermediate level of sequence conservation (53–59%) with members of the same protein family from cow, horse, rat, rabbit, mouse and guinea pig (1). There is no correlation between IgE binding to Can f 5 and binding to Can f 1, Can f 2 or Can f 3 (1).

Compiled By

Author: RubyDuke Communications

Reviewer: Dr. Magnus Borres

 

Last reviewed: December 2020

References
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. Uriarte SA, Sastre J. Clinical relevance of molecular diagnosis in pet allergy. Allergy. 2016;71(7):1066-8.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. Schoos AM, Chawes BL, Bloch J, Hansen B, Stokholm J, Bønnelykke K, et al. Children Monosensitized to Can f 5 Show Different Reactions to Male and Female Dog Allergen Extract Provocation: A Randomized Controlled Trial. J Allergy Clin Immunol Pract. 2020;8(5):1592-7.e2.
  12. Liccardi G, Calzetta L, Salzillo A, Apicella G, Piccolo A, Di Maro E, et al. Dog allergy: can a prevalent or exclusive sensitization to Can f 5 be considered a lucky or negative event in real life? Eur Ann Allergy Clin Immunol. 2018;50(6):283-5.
  13. Nordlund B, Konradsen JR, Kull I, Borres MP, Önell A, Hedlin G, et al. IgE antibodies to animal-derived lipocalin, kallikrein and secretoglobin are markers of bronchial inflammation in severe childhood asthma. Allergy. 2012;67(5):661-9.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. González-de-Olano D, Gandolfo-Cano M, de-Calzada-Bustingorri MP, González-Mancebo E, de-Andrés-Martín A, Cuesta-Herranz J, et al. Prevalence of allergy to human seminal fluid among women with allergy to male dog and sensitization to Can f 5. Clin Exp Allergy. 2018;48(10):1368-70.