e94 rFel d 1 Cat

Allergens within Epidermals and Animal Proteins

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  • Latin name: Felis domesticus
  • Common names: Cat I, Ag4, Fel d 1-related protein
  • Source material: An E. coli strain carrying a cloned cDNA encoding Felis domesticus allergen Fel d 1

Cat allergen components

Available ImmunoCAP®:

Summary

The Cat is a small feline carnivorous mammal of the subspecies Felis domesticus. The Domestic cat is now considered a subspecies of the Wild cat. There are dozens of breeds of Cats.

Several studies have reported that Cat allergen is a risk factor for childhood asthma (1-3).  Recent studies have also reported the contrary, that sensitisation to Cat allergen protects against allergic disease (4-5).

The majority of studies, however, have reported that Cat allergens are associated with increased allergic disease. Allergy has been reported to Cat dander, Cat saliva, Cat urine and Cat serum. But Cat serum and Cat urine collected by bladder puncture have no detectable levels of Fel d 1 (1).

Different prevalences of sensitization to cat allergens in atopic patients have been reported from many countries all over the world and figures range from 1-75 % (6-12).

Cat allergen is ubiquitous and may be found in many environments, transferred even by an individual’s hair.  This kind of phenomenon results in Cat allergen being found even in environments with strict allergen avoidance measures (13). Even upholstered seats in workplaces may constitute significant reservoirs of Cat allergens (14).

Individuals may be sensitised to a range of Cat allergens and, by extension, to sources for these allergens. For example, analyses of sera from 43 individuals with a history of Cat allergy showed that 39.5% were positive to Cat pelt, 37.5% to Cat saliva, and 12% each to Cat urine and serum. The Cat pelt and saliva extracts contained Fel d 1, but Cat serum and Cat urine collected by bladder puncture had no detectable levels of this allergen (1). The pelt allergens were mainly of salivary origin (15). Early studies reported that allergens from different Cat breeds appear to be closely related (16).

At least 13 serum-related and 8 dander-related antigens have been identified in Cat dandruff and hair (17), but Fel d 1 is the most important (18). Sizes range from 10 to 66 kDa (19-20).

The following allergens have been characterised.

  • Fel d 1, a uteroglobin-like protein (21).
  • Fel d 2, serum albumin (22-23).
  • Fel d 3, cystatin, a cysteine protease inhibitor (24).
  • Fel d 4, a Lipocalin (25).
  • Fel d 5 (26).
  • Fel d 6 (26).
  • Fel d 7 (26).
  • See Cat dander e1 and Cat serum albumin e220 for further details.
Allergens from Felis domesticus listed by IUIS*
Fel d 1 Fel d 2 Fel d 3
Fel d 4 Fel d 5w Fel d 6w
*International Union of Immunological Societies (www.allergen.org) Jan. 2008.


e94 rFel d 1

Recombinant non-glycosylated protein produced in an E. coli strain carrying a cloned cDNA encoding Felis domesticus allergen Fel d 1

Common names: Cat I, Ag4, Fel d 1-related protein
Biological function: Uteroglobin-like  protein
Mw: 38 kDa

The allergen is a 38 kDa dimer composed of two 19 kDa subunits. Each 19 kDa subunit comprises 2 disulfide-linked polypeptide chains, a light alpha-chain and a heavy beta-chain containing an N-linked oligosaccharide (39)

Allergen description

Although more than 12 allergens have been identified in Cat, Fel d 1 (27-38) is the most important, eliciting IgE responses in 80% to 90% of patients with Cat allergy and accounting for 60% to 90% of the total allergenic activity of Cat extracts (21,40-41).

Fel d 1 is found in Cat hair, dander and saliva. Fel d 1 was found to be significantly higher at the base than the tip of the hair (42). A study that tried to demonstrate that Fel d 1 can accumulate on Cat skin without licking, i.e., that Fel d 1 originates from skin, found that Fel d 1 is in fact produced by Cat skin (43-44). Fel d 1 levels on the skin are dramatically higher on the facial area than on the chest of the Cat. Washing reduces levels of this major allergen on Cat skin and fur, but the accumulation on skin is restored within 2 days (45).

The allergen is produced primarily in Cat sebaceous glands and, to a lesser extent, by basal squamous epithelial cells, from which it is secreted onto the skin and fur (46). It is also produced, though to an lesser extent, in salivary glands and excreted into the saliva (18,47). The sublingual salivary glands and the anal glands are also involved in production of the allergen. The allergen is thought to be under hormonal control; male Cats produce more Fel d 1 than female Cats, castration reduces its production, and testosterone injections into castrated Cats allow recovery of production (48-49). The presence of Fel d 1 has also been demonstrated in the serous cells of the lacrimal gland (50).

Long- and short-haired Cats produce this allergen. The allergen is carried on particles ranging from less than a micrometre to greater than 20 micrometres in mean aerodynamic diameter. At least 15% of this allergen is carried on particles less than 5 micrometres in diameter (51-52).

Cat allergy is unique among allergies to mammals in that the major allergen Fel d 1 is an uteroglobin-like protein and not a lipocalin. Its function is not known, but researchers have proposed that it is involved in protecting dry epithelia, which would be a function parallel to uteroglobin protecting wet epithelia. Since Cats lick themselves and each other extensively, coating their pelts with this protein may be part of this or another essential biological function (53).

Fel d 1 is secreted in copious amounts and accumulates in house dust. Fel d 1 levels in domestic living rooms are not related to Cat colour or hair length (54). In some women with a Cat at home, the human hair constitutes a significant reservoir of Fel d 1. The amounts of Cat allergen involved might contribute to allergic sensitisation when released in Cat-free environments (55). Transfer through human hair may help explain why Cat allergen is found even in environments with strict allergen avoidance measures. Hair may be an important means of transfer and deposition of Cat allergen in schools (13).  The concentrations of Cat (Fel d 1) and Dog (Can f 1) allergens may even be higher in dust collected in schools than in homes (56).  Similarly, the highest levels of Fel d 1 have been found in homes with a Cat, but high levels have also been found in homes of allergy patients who did not have a Cat but visited others with Cats (57). Upholstered seats in workplaces have also been reported to constitute a significant reservoir of Cat allergens (and also of House dust mites) (14).

Recombinant Fel d 1 shows biologic activity similar to that of the native form (58). Recombinant Fel d 1, consisting of chain 2 and chain 1 fused together without an additional linker, seem to have immunological properties indistinguishable from the natural heterodimeric protein (30). In a study of 258 Cat-allergic individuals, excellent quantitative correlation between IgE and IgG antibody binding to rFel d 1 and nFel d 1 was demonstrated (33).

In a study of sera of 509 Cat-allergic individuals, selected on the basis of the presence of Cat serum-specific IgE and tested by RAST for IgE reactivity to purified Fel d 1, Cat albumin (CA), or both, natural and recombinant Fel d 1 exhibited similar results: 94.1% and 96.1% positive test results, respectively. The addition of determining Cat albumin (16.7% positive sera) resulted in a decrease in the number of discrepancies between purified allergens and whole extract to 2.8%. In 2% of all sera, sensitisation to Cat was largely explained by IgE reactivity to Cat albumin. The authors concluded that natural and recombinant Fel d 1 are good candidates for replacing Cat dander extracts in diagnostics for Cat allergy (34).

Recombinant hypoallergenic Fel d 1 with reduced IgE binding capacities and retained T cell reactivity may therefore be of value in the assessment of Cat allergy and in immunotherapy (59).

 

e220 nFel d 2

Native cat serum albumin purified from Felis domesticus

Biological function: Serum albumin
Mw: 65-69 kDa

Allergen description

Cat albumin (Fel d 2), a 65-69 kDa protein, is found in serum, dander and saliva (22-23). About 15%-25% of Cat-allergic individuals are sensitive to Cat albumin, and for a few patients this may be the predominant allergen (17,20,60-63).

Albumins from Cat, Dog and Horse share some epitopes that account for the cross-reactivity observed in around a third of patients sensitised to Cat, Dog and Horse, but more than 50% of specific IgE that cross-reacts among these 3 animals is directed to allergens other than albumin (64-65). Significant cross-reactivity has been reported between Cat hair and Dog dander in specific IgE inhibition studies, whereas saliva and urine were more species-specific (66). Although a high degree of sequence homology exists among different animal albumins, a remarkable variability of IgE cross-reactivities has been observed, indicating that some patients are sensitised preferentially against certain albumins. Most of the patients allergic to albumins, however, reacted to Dog, Cat, and Horse albumin, which also bound a high percentage of albumin-specific IgE (67).

Some Cat-allergic individuals are likely to experience allergic symptoms following the consumption of Pork. Inhibition experiments showed that the spectrum of IgE reactivity to Cat serum albumin completely contained IgE reactivity to Porcine serum albumin. Sensitisation to Cat appears to be the primary event. Sensitisation to Cat serum albumin should be considered a useful marker of possible cross-sensitisation not only to Porcine serum albumin but also to other mammalian serum albumins (24).

Compiled by Dr Harris Steinman, harris@zingsolutions.com

References:

    1. Anderson MC, Baer H, Ohman JL Jr. A comparative study of the allergens of cat urine, serum, saliva, and pelt.
      J Allergy Clin Immunol 1985;76(4):563-9
    2. Lau S, Illi S, Platts-Mills TA, Riposo D, Nickel R, Gruber C, Niggemann B, Wahn U; Multicentre Allergy Study Group. Longitudinal study on the relationship between cat allergen and endotoxin exposure, sensitization, cat-specific IgG and development of asthma in childhood--report of the German Multicentre Allergy Study (MAS 90). Allergy 2005;60(6):766-73
    3. Liccardi G, Martin S, Lombardero M, D’Amato M, Barber D, D’Amato G, Cazzola M. Cutaneous and serological responses to cat allergen in adults exposed or not to cats. Respir Med 2005;99(5):535-44
    4. Platts-Mills T, Vaughan J, Squillace S, Woodfolk J, Sporik R. Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study.
      Lancet 2001;357(9258):752-6
    5. Perzanowski MS, Ronmark E, Platts-Mills TA, Lundback B. Effect of cat and dog ownership on sensitization and development of asthma among preteenage children. Am J Respir Crit Care Med 2002;166(5):696-702
    6. Boulet LP, Turcotte H, Laprise C, Lavertu C, Bedard PM, Lavoie A, Hebert J. Comparative degree and type of sensitization to common indoor and outdoor allergens in subjects with allergic rhinitis and/or asthma.
      Clin Exp Allergy 1997;27(1):52-9
    7. Schutz-Kiss D, Popp W, Wagner C, Reiser K, Havelec L, Zwick H. Sensitization to inhaled allergens in the Vienna population. [German] Wien Klin Wochenschr 1995;107(11):331-5
    8. Panzani RC, Mercier P, Delord Y, Riva G, Falagiani P, Reviron D, Auquier P. Prevalence of patent and latent atopy among a general normal adult population in the south east of France by RAST investigation and correlation with circulating total IgE levels. Allergol Immunopathol (Madr) 1993;21(6):211-9
    9. Brown CW, Hawkins L. Allergy prevalence and causal factors in the domestic environment: results of a random population survey in the United Kingdom. Ann Allergy Asthma Immunol 1999;83(3):240-4
    10. Jedrychowski W, Flak E, Mroz E, Lis G. Sensitization to common airborne allergens in school children with bronchial asthma. [Polish] Przegl Lek 2000;57(9):441-5
    11. Guneser S, Atici A, Cengizler I, Alparslan N. Inhalant allergens: as a cause of respiratory allergy in east Mediterranean area, Turkey. Allergol Immunopathol (Madr) 1996;24(3):116-9
    12. Perzanowski MS, Ronmark E, Nold B, Lundback B, Platts-Mills TA. Relevance of allergens from cats and dogs to asthma in the northernmost province of Sweden: schools as a major site of exposure. J Allergy Clin Immunol 1999;103(6):1018-24
    13. Karlsson AS, Renstrom A. Human hair is a potential source of cat allergen contamination of ambient air.
      Allergy 2005 Jul;60(7):961-4
    14. Perfetti L, Ferrari M, Galdi E, Pozzi V, Cottica D, Grignani E, Minoia C, Moscato G. House dust mites (Der p 1, Der f 1), cat (Fel d 1) and cockroach (Bla g 2) allergens in indoor work-places (offices and archives).
      Sci Total Environ 2004;328(1-3):15-21
    15. Anderson MC, Baer H. Allergenically active components of cat allergen extracts.
      J Immunol 1981;127:972-5
    16. Ohman JL, Lowell FC, Bloch KJ. Allergens of mammalian origin. III. Properties of a major feline allergen.
      J Immunol 1974;113:1667-8
    17. Wallenbeck I, Einarsson R. Identification of dander-specific and serum-specific allergens in cat dandruff extract.
      Ann Allergy 1987;59:131-4
    18. Wood RA, Laheri AN, Eggleston PA. The aerodynamic characteristics of cat allergen. Clin Exp Allergy 1993;23:733-9
    19. Kleine-Tebbe J, Kleine-Tebbe A, Jeep S, Schou C, Lowenstein H, Kunkel G. Role of the major allergen (Fel d I) in patients sensitized to cat allergens. Int Arch Allergy Immunol 1993;100(3):256-62
    20. Duffort O, Carreira J, Lombardero M. Characterization of the main IgE-binding components of cat dander. Int Arch Allergy Appl Immunol 1987;84(4):339-44
    21. De Groot H, van Swieten P, van Leeuwen J, Lind P, Aalberse RC. Monoclonal antibodies to the major feline allergen Fel d I. I. Serologic and biologic activity of affinity-purified Fel d I and of Fel d I-depleted extract. J Allergy Clin Immunol 1988;82(5 Pt 1):778-86
    22. Hilger C, Grigioni F, Hentges F. Sequence of the gene encoding cat (Felis domesticus) serum albumin. Gene 1996;169:295-6
    23. Hilger C, Kohnen M, Grigioni F, Lehners C, Hentges F. Allergic cross-reactions between cat and pig serum albumin. Study at the protein and DNA levels.
      Allergy 1997;52(2):179-87
    24. Ichikawa K, Vailes LD, Pomes A, Chapman MD. Identification of a novel cat allergen –cystatin. Int Arch Allergy Immunol 2001;124(1-3):55-6
    25. Smith W, Butler AJ, Hazell LA, Chapman MD, Pomes A, Nickels DG, Thomas WR. Fel d 4, a cat lipocalin allergen.
      Clin Exp Allergy 2004;34(11):1732-8
    26. Allergome http://www.allergome.org 2005
    27. Rogers BL, Morgenstern JP, Garman RD, Bond JF, Kuo MC. Recombinant Fel d.I: Expression, purification, IgE binding and reaction with cat-allergic human T cells.
      Mol Immunol 1993;30(6):559-68
    28. Seppala U, Hagglund P, Wurtzen PA, Ipsen H, Thorsted P, Lenhard T, Roepstorff P, Spangfort MD. Molecular characterization of major cat allergen Fel d 1: expression of heterodimer by use of a baculovirus expression system.
      J Biol Chem 2005;280(5):3208-16
    29. Andersson TN, Ekman GJ, Gronlund H, Buentke E, Eriksson TL, Scheynius A, Van Hage-Hamsten M, Gafvelin G. A novel adjuvant-allergen complex, CBP-rFel d 1, induces up-regulation of CD86 expression and enhances cytokine release by human dendritic cells in vitro.
      Immunology 2004;113(2):253-9
    30. Kaiser L, Gronlund H, Sandalova T, Ljunggren HG, van Hage-Hamsten M, Achour A, Schneider G. The crystal structure of the major cat allergen Fel d 1, a member of the secretoglobin family.
      J Biol Chem 2003;278(39):37730-5
    31. Kaiser L, Gronlund H, Sandalova T, Ljunggren HG, Schneider G, van Hage-Hamsten M, Achour A. Production, crystallization and preliminary crystallographic study of the major cat allergen Fel d 1. Acta Crystallogr D Biol Crystallogr 2003;59(Pt 6):1103-5
    32. Gronlund H, Bergman T, Sandstrom K, Alvelius G, Reininger R, Verdino P, Hauswirth A, Liderot K, Valent P et al. Formation of disulfide bonds and homodimers of the major cat allergen Fel d 1 equivalent to the natural allergen by expression in Escherichia coli.
      J Biol Chem 2003;278(41):40144-51
    33. Vailes LD, Sun AW, Ichikawa K, Wu Z, Sulahian TH, Chapman MD, Guyre PM. High-level expression of immunoreactive recombinant cat allergen (Fel d 1): Targeting to antigen-presenting cells. J Allergy Clin Immunol 2002;110(5):757-62
    34. van Ree R, van Leeuwen WA, Bulder I, Bond J, Aalberse RC. Purified natural and recombinant Fel d 1 and cat albumin in in vitro diagnostics for cat allergy. J Allergy Clin Immunol 1999;104(6):1223-30
    35. Slunt JB, Rogers BL, Chapman MD. IgE antibodies to recombinant forms of Fel d I: dichotomy between fluid-phase and solid-phase binding studies. J Allergy Clin Immunol 1995;95(6):1221-8
    36. Rogers BL, Bond JF, Craig SJ, Nault AK, Segal DB, Morgenstern JP, Chen MS, Bizinkauskas CB, Counsell CM, Lussier AM et al. Potential therapeutic recombinant proteins comprised of peptides containing recombined T cell epitopes. Mol Immunol 1994;31(13):955-66
    37. Bond JF, Brauer AW, Segal DB, Nault AK, Rogers BL, Kuo MC. Native and recombinant Fel dI as probes into the relationship of allergen structure to human IgE immunoreactivity.
      Mol Immunol 1993;30(16):1529-41
    38. Keating KM, Segal DB, Craig SJ, Nault AK, Semensi V, Wasserman AS, Counsell CM, Bond JF. Enhanced immunoreactivity and preferential heterodimer formation of reassociated Fel d I recombinant chains.
      Mol Immunol 1995;32(4):287-93
    39. Kristensen AK, Schou C, Roepstorff P. Determination of isoforms, N-linked glycan structure and disulfide bond linkages of the major cat allergen Fel d1 by a mass spectrometric approach.
      Biol Chem 1997;378(8):899-908
    40. Lowenstein H, Lind P, Weeke B. Identification and clinical significance of allergenic molecules of cat origin. Part of the DAS 76 Study. Allergy 1985;40:430-7
    41. Ohman JL, Kendall S, Lowell FC. IgE antibody to cat allergens in an allergic population. J Allergy Clin Immunol 1977;60:317-23
    42. Mata P, Charpin D, Charpin C, Lucciani P, Vervloet D. Fel d I allergen: skin and or saliva? Ann Allergy 1992;69(4):321-2
    43. Dabrowski AJ, Van der Brempt X, Soler M, Seguret N, Lucciani P, Charpin D, Vervloet D. Cat skin as an important source of Fel d I allergen. J Allergy Clin Immunol 1990;86(4 Pt 1):462-5
    44. Jalil-Colome J, de Andrade AD, Birnbaum J, Casanova D, Mege JL, Lanteaume A, Charpin D, Vervloet D. Sex difference in Fel d 1 allergen production. J Allergy Clin Immunol 1996;98(1):165-8
    45. Carayol N, Birnbaum J, Magnan A, Ramadour M, Lanteaume A, Vervloet D, Tessier Y, Pageat P. Fel d 1 production in the cat skin varies according to anatomical sites.
      Allergy 2000;55(6):570-3
    46. Charpin C, Mata P, Charpin D, Lavaut MN, Allasia C, Vervloet D. Fel d I allergen distribution in cat fur and skin.
      J Allergy Clin Immunol 1991;88(1):77-82
    47. Purohit A, de Blay F.  Cat allergen eviction with the cat in situ – is it worthwhile?
      Allergy Clin Immunol Int 1999;11:207-10
    48. Charpin C, Zielonka T, Charpin D, Ansaldi JL, Allasia C, Vervloet D. Effects of castration and testosterone on Fel d 1 production by sebaceous glands of male cats. II. Morphometric assessment.
      Clin Exp Allergy 1994;24:1174-8
    49. Zielonka T, Charpin D, Ansaldi JL, Allasia JL, Vervloet D. Effects of castration and testosterone on Fel d 1 production by sebaceous glands of male cats. I. Immunologic assessment.
      Clin Exp Allergy 1994;12:1169-73
    50. van Milligen FJ, Vroom TM, Aalberse RC. Presence of Felis domesticus allergen I in the cat’s salivary and lacrimal glands.
      Int Arch Allergy Appl Immunol 1990;92(4):375-8
    51. Luczynska CM, Li Y, Chapman MD, Platts-Mills TAE. Airborne concentrations and particle size distribution of allergen derived from domestic cats (Felis domesticus).
      Am Rev Resp Dis 1990;141:361-7
    52. Phipatanakul W. Animal allergens and their control. Curr Allergy Asthma Rep 2001;1(5):461-5
    53. Karn RC. The mouse salivary androgen-binding protein (ABP) alpha subunit closely resembles chain 1 of the cat allergen Fel d I. Biochem Genet 1994;32(7-8):271-7
    54. Siebers R, Holt S, Peters S, Crane J, Fitzharris P. Fel d 1 levels in domestic living rooms are not related to cat color or hair length. J Allergy Clin Immunol 2001;108(4):652-3
    55. Liccardi G, Barber D, Russo M, D’Amato M, D’Amato G. Human hair: an unexpected source of cat allergen exposure. Int Arch Allergy Immunol 2005;137(2):141-4
    56. 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
    57. Quirce S, Dimich-Ward H, Chan H, Ferguson A, Becker A, Manfreda J et al. Major cat allergen (Fel d I) levels in the homes of patients with asthma and their relationship to sensitization to cat dander. Ann Allergy Asthma Immunol 1995;75(4):325-30
    58. Witteman AM, Stapel SO, Perdok GJ, Sjamsoedin DH, Jansen HM, Aalberse RC, van der Zee JS. The relationship between RAST and skin test results in patients with asthma or rhinitis: a quantitative study with purified major allergens J Allergy Clin Immunol 1996;97(1 Pt 1):16-25
    59. Saarne T, Kaiser L, Gronlund H, Rasool O, Gafvelin G, van Hage-Hamsten M. Rational design of hypoallergens applied to the major cat allergen Fel d 1.
      Clin Exp Allergy 2005;35(5):657-63
    60. Stokes CR. Turner MW. Isolation and characterization of cat allergens.
      Clin Allergy 1975;5:241-54
    61. Brighton WD von, Topping MD, Berry JB. Allergene aus Katzenfell.
      Allergologie 1981;5:270-5
    62. Ickovic MR, Rabillon J, Dandeu JP, David JP, David B. Human hypersensitivity to cat allergens: Fel d I and serum albumin. (abstract) Allergy Clin Immunol 1991;(suppl 1):198
    63. Immunol 1991;(suppl 1):198 (abstract)
    64. 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
    65. Cabanas R, Lopez-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
    66. Viander M, Valovirta E, Vanto T, Koivikko A. Cross-reactivity of cat and dog allergen extracts. RAST inhibition studies with special reference to the allergenic activity in saliva and urine. Int Arch Allergy Appl Immunol 1983;71(3):252-60
    67. Spitzauer S, Pandjaitan B, Soregi G, Muhl 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

2009



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