e102 rCan f 2 Dog

Allergens within Epidermals and Animal Proteins

Print Print icon Tell a friend Tell a friend icon
  • Latin name: Canis familiaris
  • Family: Canidae
  • Common names: Dog
  • Source material: An E. coli strain carrying a cloned cDNA encoding Canis familiaris allergen

Recombinant allergen
rCan f 2 (32-33).

Biological function
Can f 2 is a lipocalin.

Mw
19 kDa.

Summary
The Dog is a relative of the Wolf, the Jackal, and the Fox, all belonging 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. Dogs through the centuries have acquired the body types and dispositions to pursue and retrieve game, 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.

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 (1-5). The concentration of allergens varies within breeds and among them (2, 6). Although allergen differences occur according to the origin 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. They may be found, for example, 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 even be higher in dust collected in schools than in homes (15). High Dog allergen levels can be found in households without a pet if the former occupants have 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 allergen 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 certainly impossible is that Dog (and Cat) allergen is 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, 25-27). 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 (28-30). Furthermore, occupational allergy to Dog allergens may also 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, 32-34).
  • Can f 2, a lipocalin (2, 32-33).
  • Can f 3, Dog serum albumin (28, 35).
  • Can f 4 (36).

Two serum proteins, alpha-1-antitrypsin and IgG, have been identified as minor allergens (2, 8).

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

Can f 2, a 19 kDa protein found in dander and saliva, previously known as Can d 2, is a lipocalin family member and has homology with Mouse urinary protein (MUP) (32, 37). 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 (35). It has also been found in salivary glands (parotid and submandibular) and liver (38). 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.

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 (39). 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.

Importantly, Dog-allergic individuals are sensitised to a heterogenous range of Dog allergens. For example, in a study of Dog-allergic 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).

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 (40). To date, many different recombinant allergens of various pollens, molds, mites, and foods, as well as 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 allergenic test products as tools in molecular allergology. Recombinant allergens are particularly useful for investigations of allergies manifesting wide cross-reactivity.

Allergen description
Can f 2, previously known as Can d 2, is a protein with a molecular weight of 19 kDa (38) 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, confirming its role as a minor allergen (2). Recombinant Can f 2 has a slightly lower concordance compared with natural Can f 2, with about a third of Dog-allergic patients found to be reacting to this recombinant allergen (33).

Compiled by Dr Harris Steinman, harris@zingsolutions.com

References:

    1. Spitzauer S, Rumpold H, Ebner C, Schweiger C, Valenta R, Gabl F, et al. 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., K.G.H. Goei, P. van Swieten, and R.C. Aalberse. Affinity purification of a major and a minor allergen from dog extract: Serologic activity of affiity-purified Can f I and Can f I-depleted extract. J Allergy Clin Immunol 1991;87:1056-1065.
    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 Mar 7;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 et al. 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;21:321-328
    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, 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 allergenspecific 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, 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
    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 Sep 15;175(6):6-3620
    35. Pandjaitan B, Swoboda I, Brandejsky-Pichler F, Rumpold H, Valenta R, et al. 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
    36. International Union of Immunological Societies Allergen Nomenclature: IUIS official list http://www.allergen.org/List.htm 2006
    37. 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):1279-1286
    38. 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
    39. 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
    40. 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.
    41. Mantyjarvi R, Rautiainen J, Virtanen T. Lipocalins as allergens. Biochim Biophys Acta 2000;1482(1-2):308-17
    42. Virtanen T. Zeller Important animal allergens are lipocalin proteins: why are they allergenic? Int Arch Allergy Immunol 1999;120:247-58
    43. 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;82:318-325
    44. 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

2006



Further Reading