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. 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.
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. 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.
Clinical Relevance
Disease severity
High-titer IgE antibodies to dog allergens are strongly associated with the diagnosis, severity, and persistence of asthma. Sensitization to Can f 2 was more common in children with severe asthma than in age-matched peers with controlled asthma. 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.
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. 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.
Simpson et al. investigated the relationship between sensitization to groups of specific allergen components and disease, including asthma, in children aged 11 years. 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. 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. 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.
Diagnostics
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. A study of 25 dog-allergic patients showed that approximately one-third reacted to Can f 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. 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, and it should be considered that all individuals who react to rCan f 2 are also reactive to rCan f 1.
Cross-Reactivity
Studies have demonstrated that all dog-sensitized patients with reactivity to Can f 2 will also react to Can f 1. 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. Can f 2 has homology with mouse urinary protein (MUP), a known allergen.
References
- Ford AW, Alterman L, Kemeny DM. The allergens of dog. I. Identification using crossed radio-immunoelectrophoresis. Clin Exp Allergy. 1989;19(2):183-90.
- Saarelainen S, Taivainen A, Rytkönen-Nissinen M, Auriola S, Immonen A, Mäntyjärvi R, et al. Assessment of recombinant dog allergens Can f 1 and Can f 2 for the diagnosis of dog allergy. Clin Exp Allergy. 2004;34(10):1576-82.
- Spitzauer S, Schweiger C, Anrather J, Ebner C, Scheiner O, Kraft D, et al. Characterisation of dog allergens by means of immunoblotting. Int Arch Allergy Immunol. 1993;100(1):60-7.
- de Groot H, Goei KG, van Swieten P, Aalberse RC. Affinity purification of a major and a minor allergen from dog extract: serologic activity of affinity-purified Can f I and of Can f I-depleted extract. J Allergy Clin Immunol. 1991;87(6):1056-65.
- Konieczny A, Morgenstern JP, Bizinkauskas CB, Lilley CH, Brauer AW, Bond JF, et al. The major dog allergens, Can f 1 and Can f 2, are salivary lipocalin proteins: cloning and immunological characterization of the recombinant forms. Immunology. 1997;92(4):577-86.
- Wintersand A, Asplund K, Binnmyr J, Holmgren E, Nilsson OB, Gafvelin G, et al. Allergens in dog extracts: Implication for diagnosis and treatment. Allergy. 2019;74(8):1472-9.
- Perzanowski MS, Ronmark E, James HR, Hedman L, Schuyler AJ, Bjerg A, et al. Relevance of specific IgE antibody titer to the prevalence, severity, and persistence of asthma among 19-year-olds in northern Sweden. J Allergy Clin Immunol. 2016;138(6):1582-90.
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- Schoos AM, Kattan JD, Gimenez G, Sampson HA. Sensitization phenotypes based on protein groups and associations to allergic diseases in children. J Allergy Clin Immunol. 2016;137(4):1277-80.
- Simpson A, Lazic N, Belgrave DC, Johnson P, Bishop C, Mills C, et al. Patterns of IgE responses to multiple allergen components and clinical symptoms at age 11 years. J Allergy Clin Immunol. 2015;136(5):1224-31.
- Nwaru BI, Suzuki S, Ekerljung L, Sjölander S, Mincheva R, Rönmark EP, et al. Furry Animal Allergen Component Sensitization and Clinical Outcomes in Adult Asthma and Rhinitis. J Allergy Clin Immunol Pract. 2019;7(4):1230-8.e4.
- Konradsen JR, Fujisawa T, van Hage M, Hedlin G, Hilger C, Kleine-Tebbe J, et al. Allergy to furry animals: New insights, diagnostic approaches, and challenges. J Allergy Clin Immunol. 2015;135(3):616-25.
- Jensen-Jarolim E, Pacios LF, Bianchini R, Hofstetter G, Roth-Walter F. Structural similarities of human and mammalian lipocalins, and their function in innate immunity and allergy. Allergy. 2016;71(3):286-94.