e102 Can f 2

Summary

Canis familiaris allergen 2 (Can f 2) is a salivary lipocalin protein and a minor allergen present in dog hair and dander extracts. Sensitivity to Can f 2 is associated with high levels of bronchial inflammation and is more common among patients with severe versus well-controlled asthma. Molecular diagnostics can utilize recombinant Can f 2 to reliably identify dog-allergic individuals sensitized to Can f 2, however it should be noted that all patients with reactivity to Can f 2 will also react to Can f 1.

Epidemiology

Worldwide distribution

Dog-allergic individuals are sensitive to a number of proteins found in dog hair and dander extracts (1). A study of 25 dog-allergic patients showed that 28% had IgE against Can f 2, while IgE reactivity was also shown to Can f 1 (52%), an 18 kDa protein (60%), a 40 kDa protein (44%), and a 70 kDa protein (48%) which was probably serum albumin, now known as Can f 3 (2).

In a study of 75 patients with clinical type I allergy against dogs, sera from 96% of subjects showed IgE antibodies reactive with Can f 1 and Can f 2 from hair/dander extract (3). In another study, the average IgE response of 41 dog-allergic patients to purified Can f 2 was only 23% compared to the IgE response to whole dog dander extract, with no IgE response in 34% of the patients, confirming the minor importance of Can f 2 for dog-allergic patients (4).

Environmental Characteristics

Source and tissue

Can f 2 is produced by tongue and parotid gland (5), and strongly expressed in skin and saliva, but not hair, serum or liver (3, 6).

Clinical Relevance

Disease severity

High-titer IgE antibodies to dog allergens are strongly associated with the diagnosis, severity, and persistence of asthma (7, 8). Sensitization to Can f 2 was more common in children with severe asthma than in age-matched peers with controlled asthma (8). In another study, multi-sensitization to three or more animal-derived components including lipocalin (e.g. Can f 2) was more common among severe asthmatics than in children with controlled asthma and also associated with increased bronchial inflammation (9).

The majority of dog-sensitized children react to more than one dog component, with higher levels of component sensitization and co-sensitization to Can f 5 and Can f 1/Can f 2 conferring the greatest risks of asthma (10). Sensitization to lipocalins including Can f 2 was found to be significantly associated with asthma, but not allergic rhinitis, in a cross-sectional cohort study of 269 children aged 1–11 years (11).

Simpson et al. investigated the relationship between sensitization to groups of specific allergen components and disease, including asthma, in children aged 11 years (12). Asthma and decreased lung function were most strongly associated with sensitization to a group of 27 components that included Can f 1, Can f 2, and Can f 3 (odds ratio 8.20; 95% CI, 3.49–19.24; p<0.001) and lower FEV1 (p<0.001), and all but one of the nine children who were sensitized to Can f 2 had asthma (12). Similar results were noted in a population-based study of 19 year olds, with sensitization to specific proteins including Can f 1, Can f 2, and Can f 5 being strongly associated with asthma (7). Additionally, a large population-based study of adults concluded that sensitization to furry animal allergen components is an important predictor of asthma, rhinitis, and markers of asthma severity with increased blood eosinophils, fractional exhaled nitric oxide (FeNO), and airway hyperreactivity (13).

Molecular Aspects

Allergenic Molecules

Allergenic lipocalins have been especially identified in furry animals, and four of the six currently-identified dog allergens are lipocalins (Can f 1, Can f2, Can f 4 and Can f 6) (14, 15). Humans mutually exchange innate immune molecules such as lipocalins with their domestic animals via skin shedding and secretions (15). Lipocalins comprise an important family of proteins that dominate the respiratory mammalian allergens, and usually carry lipids (or other hydrophobic/amphiphilic compounds) within a large calyx-like cavity formed by a characteristic molecular β-barrel fold (15). Ligand specificity of lipocalins is regulated by amino acid residues that line their binding pocket (15).

Can f 2, previously known as Can d 2, is a salivary lipocalin protein and a minor allergen present in dog hair and dander extracts (5). The protein has a molecular weight ranging from 19–27 kDa (5).

Cross-reactivity

Studies have demonstrated that all dog-sensitized patients with reactivity to Can f 2 will also react to Can f 1 (2, 14). Can f 2 shows limited, patient-dependent cross-reactivity with Fel d 4 (a cat allergen), as about a fifth (22%) of the sequence is identical (14). Can f 2 has homology with mouse urinary protein (MUP), a known allergen (5). 

Diagnostic Relevance

In vitro Diagnosis

Recombinant Can f 2 (rCan f 2) is immunologically concordant with the natural allergen Can f 2 and exhibits comparable antibody-binding capacities (2). A study of 25 dog-allergic patients showed that approximately one-third reacted to Can f 2 (2). While rCan f 2 can be reliably used to identify dog-allergic individuals sensitized to Can f 2, sensitivity for detecting dog allergy increases if multiple allergen candidates are assayed (2). Sensitization to Can f 1, Can f 2, Can f 3 and Can f 5 identifies less than half of those with IgE to dog (12), and it should be considered that all individuals who react to rCan f 2 are also reactive to rCan f 1 (2).

Compiled By

Author: RubyDuke Communications

Reviewer: Dr. Magnus Borres

Last reviewed: December 2020