e220 Fel d 2

Summary                   

Fel d 2, the cat serum albumin, is a minor cat dander allergen with high cross-reactivity to other mammalian serum albumins. In cat-allergic patients, Fel d 2 sensitization is almost always associated with sensitization to a major allergen, usually Fel d 1.

The clinical relevance of Fel d 2 sensitization as an inhaled or contact allergen is associated with asthma, allergic rhinitis and atopic dermatitis but its contribution is difficult to ascertain given the constant association with other allergens. Cross-reactivity between Fel d 2 and pork serum albumin Sus s 1 is clinically relevant in the pork-cat syndrome, where Fel d 2 can be the primary sensitizer [1]. Pork-cat syndrome can present with variable symptoms, from anaphylaxis to urticaria.

Epidemiology

Worldwide distribution

Cat allergens are among the most important causes of IgE-mediated allergic disease world-wide. The prevalence of sensitization to cats is approximately 10–15% in adults. Fel d 2 binds IgE from approximately 17% of cat-sensitized subjects and up to 50% of cat-allergic patients [2, 3]. Thus, in terms of prevalence among cat-sensitized subjects, Fel d 2 is considered an intermediate allergen [4] or a minor allergen [3].

Fel d 2 sensitization is usually shown as co-sensitization alongside other cat allergens, mainly Fel d 1 [2, 3, 5, 6].

In several studies of patients with a history of rhinitis/asthma, 10–26% tested positive to this allergen in skin prick tests [7-9].

In a study investigating IgE binding to Fel d 2 in a mixed (for gender and age) asthmatic population irrespective of cat allergy, 2.2% of male and 2.4% of female patients displayed IgE binding to Fel d 2 [10]. Another study found that sensitization to Fel d 2 reached 4.5% in asthmatic samples, whereas in samples from a random population Fel d 2 sensitization was only 0.8%; the overall frequency across both groups was 2.3% [11].

Taxonomy

Environmental characteristics                       

Risk factors

Consumption of pork can lead to allergy symptoms in an estimated 3-10% of cat allergic individuals [3]. Since the spectrum of IgE reactivity to cat serum albumin contains reactivity to porcine serum albumin, however, the primary sensitization is to cat in this case [1].

Clinical relevance

Food allergy: pork-cat syndrome

Pork-cat syndrome may present with variable symptoms, from anaphylaxis to urticaria. Pork-cat syndrome is an IgE-mediated hypersensitivity reaction which occurs upon ingestion of pork meat (containing pork serum albumin Sus s 1) in a subject previously sensitized to Fel d 2 [1, 3].

Atopic ildren with atopic dermatitis (AD) had higher levels of Fel d 2-specific IgE compared to children without AD [12].

In a study which included 2 years’ follow up of 304 early years children (median age 13 months) with atopic dermatitis and/or food allergies (but not asthma) at baseline showed that sensitization to Fel d 2 was between 8–12%. Sensitization to Fel d 2 was the least likely of the cat allergens included, with 25% of children affected [13].

Asthma and allergic rhinitis

There is evidence that more severe respiratory symptoms and a higher risk of having asthma are associated with the sensitization to cat, dog and horse serum albumin [7].

Cat-sensitized asthmatic pediatric patients with higher levels of IgE to Fel d 2 serum albumin, Fel d 4 and Fel d 7 lipocalins are more likely to have higher biomarkers of type 2 inflammation such as FeNO, and reduced lung function [6].

In other studies, Fel d 2 sensitization has been associated with symptoms of asthma and moderate to severe allergic rhinitis [14], worse asthma control, quality of life, increased exercise-induced asthma, increased ocular and nasal symptoms and more frequent use of asthma medication [8]. However, others failed to identify a significant association between Fel d 2 sensitization and asthma exacerbations [10].

Contact allergy

Fel d 2 cross-reactivity with pork serum albumin Sus s 1 may be involved in occupational asthma in workers from the meat industry [3].

Specific molecules

Fel d 2 displays high cross-reactivity to other mammalian serum albumins, preventing its use as a marker allergen.

Cross-reactive molecules

Fel d 2 displays high cross-reactivity with mammalian serum albumins, with clinical relevance as an inhaled, ingested and contact allergen.

Individuals with Fel d 2 sensitization may cross-react with chicken serum albumin Gal d 5, present in chicken meat and in egg yolk [3].

Molecular aspects                  

Biochemistry

Fel d 2 is a 69 kDa protein belonging to the family of serum albumins [15]. Serum albumins are thermolabile, highly conserved globular proteins of 65–69 kDa synthesized in the liver and secreted into plasma and other body fluids, explaining their presence in mammalian dander, serum, meat, milk, and urine [3]. Fel d 2 aminoacid sequence displays an identity of 87% with dog serum albumin Can f 3 and 76 – 78% with bovine, horse and Guinea pig serum albumins [3].

Immunotherapy

Subcutaneous immunotherapy (SCIT) using cat extract showed significant efficacy after 3, 6 and 12 months [8, 9]. Cat allergic patients that were sensitized to cat allergens other than Fel d 2 appeared to experience more symptoms improvement following their SCIT course [8].

Fel d 2 by itself, being a minor and cross-reactive allergen, is not employed as the basis of any therapeutic approach at the molecular level [3]

Diagnostic relevance              

Cross-Reactivity

Structural homology with shared epitopes between Fel d 2 and other serum albumins explains IgE cross-reactivity that may be clinically relevant. Fel d 2 cross-reactivity with canine (Can f 3), equine (Equ c 3) and pig (Sus s 1) serum albumins is described [2, 3, 16]. Cross-reactivity is observed in about a third of patients sensitized to cat, dog and horse albumins.

In a study of 273 cat-sensitized patients (of whom 187 owned a cat), 40 (15%) were sensitized to Fel d 2. Among these 40 patients, 29 were considered a primary sensitization to Fel d 2 and 11 were attributed to cross-reactivity with Can f 3 [17].

For the diagnosis of pork-cat syndrome, a detailed history and specific IgE tests for Fel d 2 and meat allergen extracts are needed [3, 16].

Cross-reactivity between Fel d 2 as a primary sensitizer and chicken serum albumin Gal d 5 may be observed as a rare event [3].

Explained results                    

Allergen information: Fel d 2 is the cat serum albumin, present in cat dander and secretions and considered a minor allergen.

Clinical relevance: Fel d 2 sensitization is associated with asthma, rhinitis, atopic dermatitis and pork-cat syndrome.

Potential cross-reactivity: Other mammalian serum albumins, especially dog serum albumin Can f 3 and pork serum albumin Sus s 1, and in some cases chicken serum albumin Gal d 5.

Author: Dr. Joana Vitte

Reviewed by: Dr. Magnus Borres