Equ c1, Horse dander
Summary
Equ c 1, a lipocalin, is a major horse allergen found in saliva, hair and to some extent, in the urine of horses (Equus caballus). It is a homodimer, glycosylated lipocalin protein (182 amino acids) weighing around 22 kDa with surfactant properties. It is found to be the most prevalent allergen (50% to 76%) among the horse-allergic patients. Sensitization to horse allergens has been reported to be between 3.6% and 16.5%, among the individuals associated with horse-related occupation, while sensitization of 5.38% has been reported among individuals with respiratory allergy. Additionally, Equ c 1 sensitization has been found to be associated with severe asthma in children as well as in adults and reportedly more prevalent in asthmatic individuals as compared to randomly-selected individuals. Further, it is also reported to be significantly associated with moderate-to-severe rhinitis among horse-sensitized patients. The main route of this horse allergen exposure is inhalation, even though it is not found to be dispersed by air to a great extent. Equ c 1 is species specific marker of sensitization. However, Equ c 1 has been found to cross-react with other lipocalins such as Can f 6 (dog), Fel d 4 (cat) and Mus m 4 (mouse) due to sequence homology. This cross-reactivity should be taken into consideration when interpreting sensitization to Equ c 1.
Epidemiology
Worldwide Distribution
Sensitization to horse allergens has been reported to be between 3.6% and 16.5%, among the individuals associated with horse-related occupation, while sensitization of 5.38% has been reported among individuals with respiratory allergy.
Equ c 1, a lipocalin, is a major horse allergen and considered as species specific marker of sensitization. A study conducted in Finland among 21 horse-allergic subjects reported sensitization to Equ c 1 in 76% of subjects. A study conducted in Sweden reported the rate of sensitization to Equ c 1 to be 50.6% among horse-allergic children, while the sensitization rate of Equ c 1 was found to be 60% among asthmatic children in another Swedish study.
The West Sweden Asthma Study was conducted among a random cohort of adults (964 asthmatics and 1042 non-asthmatics) for their sensitization to various aeroallergens. The sensitization of Equ c 1 was found to be 6.3% among males and 5.8% among females. Also, it was interesting to note that the sensitization rate significantly reduced with increasing age (p<0.01) with maximum sensitization in adults with age ≤30 years and minimum in 61 to 75 years elderly. Further, based on the same West Sweden Asthma Study among 1103 randomly selected adults, sensitization to Equ c 1 was found in 2.1%.
A retrospective study conducted among 1255 allergic individuals in Czech Republic found a sensitization of 6.2% to horse allergen Equ c 1. Another study conducted in Spain among 159 animal-sensitized (dog/cat/horse) patients reported 70% to be sensitized to Equ c 1, while 60% were found to be monosensitized to Equ c 1. Moreover, the pet sensitization profiles evaluated by component resolved diagnosis in two general pediatric populations found Equ c 1 sensitization to be 2% in a Japanese cohort as compared to 3% in a Swedish cohort.
Clinical Relevance
Disease severity
Equ c 1 is reported to be the major allergen of horse and found to be associated with severe asthma in children as well as in adults.
Sensitization to Equ c 1 was found to be significantly more prevalent (p<0.001) in asthmatic individuals (11.8%) as compared to randomly selected individuals (2%) as shown in the West Sweden Asthma Study. Also, sensitization to Equ c 1 was found to be significantly more frequent (p=0.03) in children with severe asthma as compared to children with controlled asthma (51% vs. 25%, respectively).
Cross-reactive molecules
IgE-mediated cross-reactivity of Equ c 1 has been demonstrated with Fel d 4 (cat), Can f 6 (dog) and Mus m 4 (mouse). A study using sera from 100 dog-allergic patients found that 73.8% of patients sensitized to Equ c 1 may be sensitized to all the three allergens i.e. Can f 6 from dog, Fel d 4 from cat and Equ c 1 from horse. They also reported that co-sensitization of Equ c 1 was co-related with Can f 6 (correlation coefficient, r = 0.41) and Fel d 4 (r=0.42). Moreover, potential cross-reactivity was predicted among the three allergens based on ELISA inhibition assays.
Interestingly, asymmetric type of cross-reactivity may be found between Equ c 1 and Mus m 1, and this may be attributed to certain unique epitopes in addition to common epitopes being observed among the pair. Equ c 1, being a dimeric protein may have some additional unique IgE epitopes as compared to a monomer protein, such as Mus m 1.
Diagnostics
Disease Severity
Equ c 1 was considered as a species-specific marker for sensitization to horse hair. However, due to recent knowledge of its cross-reactivity with cat and dog lipocalin (Fel d 4 and Can f 6 respectively), it is now considered for horse allergy relatively, along with sensitization to cat and dog allergens.
Exposure
The main route of horse allergen exposure is through inhalation, however, the allergen is not found to be dispersed by air to a great extent. The hidden exposure of Equ c 1 through secondary exposures, such as clothes, vehicles or dust may induce allergic reactions in susceptible individuals.
Further, it was considered that Curly horses or certain breeds of horses are hypoallergenic as they release less allergen levels in the air. However, a study conducted using 224 hair samples from 32 breeds of horses found no correlation between production of allergens or release of allergens in the air with the hypo-allergenicity of the breed of Curly horses. Also, the amount of allergens released in the air during grooming were not found to be significantly different for Curly horses as compared to other breeds which were not considered hypoallergic.
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