Can f 1
Summary
Canis familiaris allergen 1 (Can f 1) is a salivary lipocalin protein and one of the major allergens present in dog hair and dander extracts. Can f 1 is found in all homes with dogs and in one-third of homes without dogs, and approximately half of all dog-allergic individuals have IgE directed exclusively to Can f 1. Increasing sensitization to Can f 1 is strongly associated with increasing severity and persistence of asthma symptoms in children and adults. In molecular diagnostics, recombinant Can f 1 is immunologically concordant with the natural allergen and can be reliably used to identify dog-allergic individuals sensitized to Can f 1.
Epidemiology
Worldwide distribution
A study of 25 dog-allergic patients showed that 52% had IgE against Can f 1, while IgE reactivity was also shown to Can f 2 (28%), 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. Several studies have demonstrated that approximately half of dog-allergic individuals have IgE directed exclusively to Can f 1.
Can f 1 particles can remain airborne for comparatively long periods of time with minimal disturbance, and due to their small particle size can be inhaled more easily than larger particles such as mite feces or pollen grains. Can f 1 is found in all homes with dogs, and in one-third of homes without dogs.
Clinical Relevance
Disease severity
IgE levels against lipocalins such as Can f 1 correlate with the severity of asthma, and sensitization to Can f 1 in childhood was significantly associated with symptoms to dog at age 16 years. Progression of allergic sensitization over time has been shown to involve IgE recognition of an increasing number of components from the sensitizing allergen source, forming the basis for the concept of molecular spreading, in which sensitization to a greater number of components from the same allergen source correlates with disease severity. Accordingly, increased bronchial inflammation in severe asthmatics is associated with multi-sensitization towards lipocalin (including Can f 1), kallikrein and secretoglobin components.
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).
Sensitization to Can f 1 was strongly associated with asthma in a population-based study of 19 year olds. In this study, high-titer IgE antibodies to cat and dog allergens were also strongly associated with the diagnosis, severity, and persistence of asthma. Similar findings have been reported for children aged 13–14 years.
A large cross-sectional and longitudinal population-based study demonstrated that sensitization to Can f 1 in childhood was strongly associated with symptoms to dog at age 16 years. Additionally, polysensitization to three or more allergen molecules from dog was a better longitudinal predictor of r dog symptoms than results of IgE tests with dog allergen extracts, respectively. Similar findings were reported in a large population-based study of adults aged 16–75 years, where the authors concluded 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 1 (rCan f 1) is immunologically concordant with the natural allergen Can f 1 and exhibits comparable antibody-binding capacities. A study of 25 dog-allergic patients showed that 52% had IgE against Can f 1. While rCan f 1 can be reliably used to identify dog-allergic individuals sensitized to Can f 1, 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.
Cross-Reactivity
All dog-sensitized patients with IgE antibodies to Can f 2 also reacted to Can f 1. Can f 1 and Fel d 7 (a lipocalin allergen found in cats) share 62% sequence identity, and cross-reactivity between these proteins seems likely.
References
- 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.
- 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.
- Schou C, Svendsen UG, Løwenstein H. Purification and characterization of the major dog allergen, Can f I. Clin Exp Allergy. 1991;21(3):321-8.
- 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.
- 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.
- 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.
- 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.
- Asarnoj A, Hamsten C, Wadén K, Lupinek C, Andersson N, Kull I, et al. Sensitization to cat and dog allergen molecules in childhood and prediction of symptoms of cat and dog allergy in adolescence: A BAMSE/MeDALL study. J Allergy Clin Immunol. 2016;137(3):813-21.e7.
- Hatzler L, Panetta V, Lau S, Wagner P, Bergmann RL, Illi S, et al. Molecular spreading and predictive value of preclinical IgE response to Phleum pratense in children with hay fever. J Allergy Clin Immunol. 2012;130(4):894-901.e5.
- Nordlund B, Konradsen JR, Kull I, Borres MP, Önell A, Hedlin G, et al. IgE antibodies to animal-derived lipocalin, kallikrein and secretoglobin are markers of bronchial inflammation in severe childhood asthma. Allergy. 2012;67(5):661-9.
- 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.
- 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.
- Konradsen JR, Nordlund B, Onell A, Borres MP, Grönlund H, Hedlin G. Severe childhood asthma and allergy to furry animals: refined assessment using molecular-based allergy diagnostics. Pediatr Allergy Immunol. 2014;25(2):187-92.
- 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.