Allergen Profile, Dog, IgE With Component Reflex

Serum

1 mL

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

Gel-barrier tube

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.^1,2 sIgE is necessary but not sufficient for eliciting an allergic response and thus generating a definitive diagnosis of allergic disease.¹ 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 diagnostic use of purified or recombinant allergens in the clinical assessment of individuals who suffer reproducible hypersensitivity reactions with exposures to an allergen at a dose tolerated by non-allergic individuals.^2-4 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.³

Sensitization to dog dander is an important risk factor for rhinoconjunctivitis and asthma.¹ 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.⁴ Dogs are an important source of indoor allergens and are considered to be a major risk factor for the development of allergic rhinitis and asthma.^2,5-9 A significant proportion of atopic subjects (about 20-40%) are sensitized to dog allergens. Dogs are dominant sensitizers in young adults with asthma¹² and IgE titers to dog proteins correlate with disease severity.⁶ Further, sensitization to dogs in childhood predicts persistence of asthma throughout the teen ages.^13,14

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

Unlike cat allergy, which is almost entirely attributable to sensitization to its major allergen, Fel d 1, the sensitization profile for dog allergy is more heterogeneous.¹⁵ A number of allergen molecules have been described in dogs (Canis familiaris).² Can f 1 and Can f 2 belong to the lipocalin family; Can f 3 is a serum albumin; and Can f 5 is a prostatic kallikrein from male dog urine. Can f 1 and Can f 5 have been classified as major allergens as their sensitization frequencies in dog dander sensitized patients are about 55% and 70%, respectively.^16-21 While Can f 2 and Can f 3 are considered minor allergens (< 50% sensitization rate),^16-19 the measurement of sIgE to these components has been shown to add diagnostic value.¹⁷

Can f 1

Can f 1 is a lipocalin protein produced by the salivary glands of dogs.¹⁵ Can f 1 cross-reactivity with the human tear lipocalin has been reported.^15,22 Can f 1 also displays some cross-reactivity with cat component Fel d 7^23,24 and may contribute to symptoms in cat as well in dog-allergic patients. A recent study found that 64% of cat dander sensitized individuals were Can f 1 IgE positive, with 32% of those individuals monosensitized to Can f 1.²¹ In Can f 1 sensitized individuals, sensitization to cat may be excluded by a negative test to Fel d 1.²⁴

A large European study of more than 700 children eight years old and younger (the ABAMSE/MeDALL study) reported that sIgE reactivity to the five dog allergen molecules tested (Can f 1, Can f 2, Can f 3, Can f 5 and Can f 6) increased with age.²⁵ This study found that sIgE to Can f 1 was superior to sIgE to dog allergen extract in diagnosing dog allergy. This study also found that sIgE reactivity to Can f 1 in childhood predicted the development of dog allergy in adolescence significantly better than IgE reactivity to dog allergen extract. Furthermore, IgE reactivity to Can f 1 was the only parameter that independently could predict future symptoms to dog.²⁵

Can f 2

Can f 1 and Can f 2 have common epitopes and most of the patients allergic to Can f 2 are co-sensitized to Can f 1.²¹ Sensitization to Can f 2 without Can f 1 sensitization is very rare.^{6,21,18,26-28} Because Can f 2 has little sequence identity or cross-reactivity to proteins of other mammals sIgE to this protein suggests dog-specific sensitization.²⁷ Structures of Can f 2 and Equ c 1 are quite similar; however, they do not show cross-reactivity.¹⁷ Asthmatic children sensitized to Can f 2 have been shown to be at a greater risk of having more severe symptoms.^6,29

Can f 3

Can f 3, dog serum albumin, is a highly cross-reactive minor allergen detected in 15% to 35% of dog-sensitized patients.^7,16 Serum albumins are abundant in saliva and dander and are highly cross-reactive molecules, although they are generally considered to be minor allergens.³⁰ 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. Cross sensitization to other furry animals via initial allergy to Can f 3 may play a role in the progression to polysensitization and clinical allergies to other animals. Uriarte et al found that sensitization to albumins was associated with more severe respiratory symptoms.²⁸

Can f 5

Can f 5 is a prostatic kallikrein that was original isolated from the urine of male dogs.³¹ Since this protein is produced in significant quantities only by non-neutered, male dogs,³² it has been suggested that mono-sensitization to Can f 5 may correlate with allergic sensitivity to male and not female dogs.^16,33 Antibodies to Can f 5 have been found in up to 70% of patients with dog allergy^{18,19,28,31,34} and approximately a third of Can f 5-positive, dog dander-sensitized patients did not have antibodies to Can f 1, Can f 2, or Can f 3.³¹

No patterns of Can f 5 cross-reactivity to allergens from other furry animals have been identified. However, cross-reactivity to human prostate-specific antigen, the major allergen in seminal plasma, has been reported.^7,35,36 Some studies have implicated sensitization to Can f 5 in cases of human seminal plasma allergy.^37-39

In a population-based study on 963 19-year-olds where associations with asthma symptoms, diagnosis, and treatment were examined, Perzanowski et al found that IgE antibodies to Can f 5 (and Fel d 1) were each associated with current asthma.⁴⁰ Sensitization to Can f 5 was also recently measured among children with severe asthma who, compared with children with controlled asthma, had an IgE response to more than 3 animal-derived allergen molecules, of which Can f 5 was one.^6,29

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).^18,28 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.^{6,18,29,41,42} A cross-sectional cohort study in 269 children found that asthma was significantly associated with sensitization to members of the lipocalin protein family.⁴² 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.²⁹ A recent study of unselected adults revealed that sensitization, particularly poly-sensitization, to furry animal allergen components is an important predictor of severity and clinical outcomes of asthma.⁴⁴