e221 Can f 3

Summary

Canis familiaris allergen 3 (Can f 3) is a serum albumin allergen found in dog dander, hair, epithelia and saliva, and very commonly in house dust. Sensitization to Can f 3 is associated with increased risks of asthma, allergic rhinitis, and concomitant asthma and allergic rhinitis. However, mono-sensitization to Can f 3 is rare, and it shares extensive cross-reactivity and sequence homology with serum albumins from other mammals such as human, pig, cattle, cat, sheep, horse, mouse and rat. As such, Can f 3 plays an important role in the polysensitization of allergic individuals and can also sensitize atopic individuals. The amounts of Can f 3 transferred by animal owners to public places may be enough to sensitize people without direct exposure to the allergen source itself.

Epidemiology

Worldwide distribution

Several studies concerning animal dander allergens have indicated the relative importance of serum albumin as an allergen (1, 2). While no serum albumin is considered to be a major allergen (i.e. among patients allergic to a given source, a purified allergen from that source to which >50% of patients react), the dog albumin Can f 3 is an intermediate allergen which is important for up to 35% of patients who are allergic to dog dander (2-4).

One study demonstrated that up to 90% of individual dog-allergic patients have dog-specific IgE directed against dog albumin (2). In contrast, another study showed that only half (48%) of dog-allergic patients had IgE against a 70 kDa protein which was probably serum albumin (now known as Can f 3) (5). Similarly, serum-specific IgE to Can f 3 was demonstrated for approximately 40% of 75 dog-allergic children and adults (6). In a more recent study of 54 children allergic to any furry animal, only about 25% were sensitive to Can f 3 (7), while a survey of 218 dog-sensitized children found that sensitization to Can f 3 was only seen as co-sensitization with other dog allergen components (8).

Serum albumins are present in animal dander and it is highly likely that contact with this dander is the major source of health problems associated with serum albumins in humans (4). Moreover, direct exposure to the mammalian source of serum albumin is not necessary to cause sensitization as the amount of allergen transferred by animal owners in public places may be sufficient to sensitize people without direct exposure to the allergen source (4). 

Environmental Characteristics

Source and tissue

Can f 3 can be found in dog hair, dander, epithelia (e.g. keratinocytes), saliva, salivary glands (parotis and submandibularis), serum, urine and liver (2, 6, 9). Dog serum albumin is a very common allergen present in house dust (1).

Clinical Relevance

Disease severity

Serum albumins are a minor allergen in animal dander, but can play a significant role as cross-reacting allergens in association with lipocalins and other environmental conditions (10). Of interest, serum albumins are able to sensitize atopic individuals (4).

Children with severe asthma had higher specific IgE levels to cat, dog and horse, and were more likely to be sensitized to a complex molecular spread of allergen components, than children with less severe disease (7). Sensitization to furry animal allergen components including Can f 3 is an important predictor or asthma, rhinitis, and markers of asthma severity with increased blood eosinophils, fractional exhaled nitric oxide (FeNO), and airway hyperreactivity (11). Sensitization to an increasing number of dog allergen components significantly increases the risk for reported dog-induced asthma and rhinitis, for example the presence of IgE to Can f 3 together with the lipocalins Can f 4 and Can f 6 confers a significant risk for a positive nasal challenge result (12).

In a large population-based study of adults aged 16–75 years, sensitizations to Can f 3, Can f 1, Can f 2, Fel d 1, polysensitization, and multi-sensitized cluster were associated with increased FeNO and eosinophil levels (11). Sensitization to Can f 3 was also associated with increased risks of current asthma, current allergic rhinitis, and concomitant asthma and allergic rhinitis (11).

Molecular Aspects

Biochemestry

Serum albumins are multifunctional proteins with very flexible structures that can change conformation easily to bind with many diverse ligands (4). Can f 3 is a mammalian serum albumin allergen with a molecular weight of 67–70 kDa (4-6, 13). Can f 3, previously known as Can d 3, is considered to be an intermediate dog allergen component (4, 14). 

Cross-reactivity

Table: Amino acid identities (%) between allergenic serum albumins. Figures in bold indicate documented IgE cross-reactivity between albumins. HSA: human serum albumin. (15)

Can f 3 displays a high homology to other mammalian albumins (9), and mono-sensitization to Can f 3 seems to be very rare (16). In a study of 200 animal-allergic patients, 30% reacted with albumins from different animals (3). In this study, despite a high degree of sequence homology among the albumins, recombinant Can f 3 bound IgE from all of the 15 patients allergic to albumin from dog, cat, guinea pig or horse (3). Similarly, other studies have demonstrated significant sequence homologies ranging from 75–90% between dog-specific IgE directed against dog albumin and albumins from mammals including human, pig, cattle, cat, sheep, mouse, and rat (2, 4, 14). A high degree of sequence homologies among albumins explains the extensive cross-reactivity of patient IgE antibodies with albumins from many species (4, 14).

In a study of 10 patients with IgE antibodies to cat dander and pork, all patients allergic to cat serum albumin also had high IgE titers to dog serum albumin, even if they had no contact with dogs (17). Boutin et al. showed that anti-cat albumin monoclonal antibodies recognized both cat and dog albumin equally, as did anti-dog albumin monoclonal antibodies, confirming cross-reactivity between cat and dog (13). Furthermore, as histamine release can be induced from basophils derived from dog-albumin-allergic patients on incubation with albumins from rat, mouse, and chicken, albumins from different species represent functional cross-reactive allergens (2).

Compiled By

Author: RubyDuke Communications

Reviewer: Dr. Magnus Borres

Last reviewed: December 2020