Allergen Profile, Cat, IgE With Component Reflex

Serum

1 mL

0.5 mL (Note: This volume does not allow for repeat testing.)

Gel-barrier tube

Allergic rhinitis and asthma are chronic inflammatory diseases leading to restrictions in the patient's quality of life and high costs for health care systems. Both diseases are associated with the presence of specific IgE (sIgE) against aeroallergens.¹ Cats are an important source of indoor allergens and are considered to be a major risk factor for the development of allergic rhinitis and asthma.^2-7 A significant proportion of atopic subjects (about 20-40%) are sensitized to cat allergens.^8,9 Cats are dominant sensitizers in young adults with asthma¹⁰ and IgE titers to cat proteins correlate with disease severity.³ Further, sensitization to these pets in childhood predicts persistence of asthma throughout the teen ages.^11,12 Recent studies have shown that the majority of individuals who are sensitized to cats do not have a cat in their home.^13,14

The diagnostic assessment of allergy starts with the patient’s clinical history and examination and is followed by an extract-based analysis to confirm the presence of specific IgE (sIgE) antibody.⁶ sIgE is necessary but not sufficient for eliciting an allergic response and thus generating a definitive diagnosis of allergic disease. Testing utilizing allergenic extracts does not lend itself to the differentiation of primary sensitization from a cross-reactivity-driven response because of the complexity of the extracts. Extracts contain most of the extractable allergenic components from the suspected sensitizer. However it is often not possible to predict the relative risk of having a systemic allergic reaction using an extract-based diagnostic test. Component Resolved Diagnostics (CRD) refers to the use of purified or recombinant allergens in the serologic assessment of individuals who suffer reproducible hypersensitivity reactions with exposures to an allergen at a dose tolerated by non-allergic individuals.⁶ This approach offers advantages over the use of a complete extract, especially in polysensitized individuals, given its usefulness for distinguishing between sensitizations specific to singular species and sensitizations due to cross-reactivity.¹⁵ Allergic sensitization to furry animals may be induced not only by direct/indirect exposure but also by a cross-reaction mechanism involving some families of allergenic proteins.

Allergen-specific IgE assays do not demonstrate absolute positive and negative predictive values for allergic disease. Clinical history must be incorporated into the diagnostic determination. Although the use of component resolved IgE testing may enhance the evaluation of potentially allergic individuals over the use of whole extracts alone, it cannot yet replace clinical history and oral food challenge in most cases. Sensitization against thus far unidentified determinants that are not found in the whole extract or in components might cause symptoms in rare cases.

Thermo Fisher ImmunoCAP® Allergen-specific IgE

Importantly, cat (Felis domesticus) dander allergic individuals are sensitized to a heterogeneous range of cat allergens.^6,16 The major cat allergen is the secretoglobin Fel d 1,¹⁶ which accounts for majority all IgE reactivity to cat dander.^17,18 All cat allergens other than Fel d 1 are considered minor allergens because less than fifty percent of cat dander sensitized individuals test positive for sIgE to these proteins. The minor cat allergens for which we have the most clinical data are the serum albumin, Fel d 2 and the lipocalin, Fel d 4.

Fel d 1

Fel d 1 is produced by the sebaceous glands cat and is found in their saliva.^16,19 This a thermostable protein is therefore present in large concentrations on skin surface and fur of cats as a result of grooming.²⁰ Cats are the only mammals for which a secretoglobulin is the primary sensitizer for allergic disease. No comparable protein has been characterized in other species. Since Fel d 1 does not have significant IgE cross-reactivity with other mammalian proteins, Fel d 1 positivity is considered to denote cat specific sensitization.²⁰ Serum-specific Immunoglobulin E (sIgE) to Fel d 1 is present in approximately 95% of patients that test positive for sIgE to cat dander.^18,21-26 Early studies showed 60-90% of overall allergenic activity to cat dander is directed against Fel d 1.¹⁶ Depending on the population tested, 40-70% percent of Fel d 1 sIgE positive patients are not sensitized to any other cat component routinely measured (Fel d 2 and Fel d 4).^23,24

A large European study of more than 4000 children eight years old and younger (the ABAMSE/MeDALL study) reported that sIgE reactivity to the three cat allergen molecules tested (Fel d 1, Fel d and Fel d 4) increased with age.²⁵ Fel d 1 was the dominant sensitizing cat allergen during the entire childhood in this population.²⁵ Consistent with other studies,^5,21,27 the ABAMSE/MeDALL study found that testing for sIgE to Fel d 1 was comparable to testing for sIgE to cat allergen extract in diagnosing cat allergy.²⁵ This study also found that sIgE to Fel d 1 in young children was more predictive of cat allergy at 16 years of age than measuring sIgE to cat allergen extract.²⁵ In the ABAMSE/MeDALL population, less than ten percent of patients were positive for Fel d 2 and/or Fel d 4 and not Fel d 1.²⁵ Testing for sIgE to Fel d 1 directly, without testing for sIgE to cat dander extract would have caused a small number of cases with non-typical sensitization profiles (about 5-10%) to be missed.^25,28

Sensitization to cats and dogs in childhood has been shown to predict the persistence of asthma throughout the teen ages ¹¹ and cat dander has been shown to be a dominant sensitizer in young adults with asthma.¹⁰ In a population-based study of 963 19-year-old Swedes, levels of sIgE to Fel d 1 were found to be strongly associated with the prevalence, severity, and persistence of asthma.²⁹ This finding was consistent with a other studies that have found that increased Fel d 1 sIgE levels can serve as a prognostic marker of future cat allergy and allergic asthma.^{2,3,21,24,25,27,30,46}

Fel d 2

The protein Fel d 2 is cat albumin.³¹ In the context of respiratory allergy, serum albumins are considered to be an uncommon cause of allergic sensitization.^31-33 Sensitization to Fel d 2 has been associated with moderate/severe rhinitis and a diagnosis of asthma in patients sensitized to other cat components.^3,26,34 Wisniewski et al. described an association between high levels of sIgE to Fel d 2 and atopic dermatitis in cat-allergic children.³⁵

Serum albumins are major allergen in meats, which underlies their importance as food allergens.³³ Most albumin sensitized patients tolerate well-cooked meat or milk as serum albumins are thermolabile. Cross-reactivity between cat and pork albumin is thought to be responsible for allergic reactions after ingestion of pork in cat-allergic individuals in a condition referred to as pork-cat-syndrome.^33,36-37 It is thought that initial environmental exposure to cat albumin causes sensitization that results in subsequent rapid onset of allergic reactions on eating pork.^36,37

Serum albumins from mammals are highly conserved both in amino acid sequence and three-dimensional structure^31,33,38 and are thought to play a significant role as cross-reacting allergens in individuals sensitized to several types of animal dander. Monosensitization to Fel d 2 or to the dog albumin, Can f 3, is very rare. The occurrence of specific IgE to Fel d 2 without sensitization to Fel d 1 could be a marker of cross-reactivity to another animal and not primary sensitization to cat.³³ As sensitization to cat and/or dog serum albumins is almost always seen in combination with specific IgE directed against major allergens, the clinical relevance of serum albumins is still undefined.

Fel d 4

Fel d 4, a lipocalin protein, is the second most frequent sIgE sensitizing component of cat dander and is positive in 30-60% of cat dander sensitized patients, depending on the population studied.^23,24,39 The great majority of patients with sensitization to Fel d 4 are also sensitized to Fel d 1.^23,24 A study involving 696 Swedish children reported that current asthma and asthma symptoms following contact with cats were associated with co-sensitization to Fel d 1 and Fel d 4.²⁴ Levels of IgE to Fel d 4, but not Fel d 1 or cat extract, were independently associated with Β-Eos count (P = .009) and total IgE in young asthmatics.³⁴ Wisniewski et al. described an association between high levels of sIgE to Fel d 4 and atopic dermatitis in cat-allergic children.³⁵

Many individuals that test positive for sIgE to cat dander also test positive for sIgE to dander from other mammals. Allergic sensitization to furry animals may be induced not only by direct/indirect exposure but also by a cross-reaction mechanism involving some families of allergenic proteins. This cosensitization is explained, in part, by to the fact that Fel d 4 has up to 60% amino acid sequence identity with lipocalins from other mammals including Can f 6 from dog, Equ c 1 from horse and other lipocalins from mouse, rabbit and rat.^40,41 Cross-reactivity between Fel d 4 and Can f 2, although the sequential identity observed in their study was less than 22%.⁴² Many patients with measurable sIgE to Fel d 4 also test positive for these other, cross-reactive components making it sometimes difficult to discern the extent to which the presence of sIgE to one or more of these components represents true clinical sensitization or simply cross-reactivity. Fel d 4 positivity in Fel d 1 negative patients suggest that cat is not the primary sensitizer.

Sensitization to Multiple Components

Multiple sensitization to cat and dog allergens during childhood has been associated to the development of subsequent allergy to dogs and cats.²⁵ Sensitization to two or more cat, dog, and horse allergen components has been associated with severe respiratory symptoms (severe asthma and rhinitis).^24,26 Poly-sensitization to multiple cat or dog components has been shown to be a risk marker for asthma in children and has been associated with increased bronchial inflammation in severe asthmatic children and young adults.^{3,24,27,34,43,44} A cross-sectional cohort study in 269 children found that asthma was significantly associated with sensitization to members of the lipocalin protein family.⁴⁵ Nordlund et al reported that a specific IgE response in children to more than three animal-derived components was more common among uncontrolled severe asthmatics compared to children with controlled asthma.⁴⁴ A recent study of unselected adults revealed that sensitization, particularly poly-sensitization, to furry animal allergen components is an important predictor of clinical outcomes of asthma and eosinophilic markers of asthma severity.⁴⁶