rFel d 1 Cat

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Cat dander e1

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Code: e94
Latin name: Felis domesticus
Common names: Cat I, Ag4, Fel d 1-related protein

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

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