To our knowledge only few studies have addressed the clinical relevance of component resolved diagnosis in dog and cat allergy. The present study is focusing on the frequency of hypersensitivity to commercially available cat and dog allergen components in adult patients with symptoms of allergy to pets.
Fel d 1, thee main feline allergen, caused sensitizations in 93.9% of patients with sensitization to feline allergen components, from which group monosensitization was found in 30 (49.2%). A study by Bjerg et al. [5] found sensitization to the Fel d 1 component in 83.7% of its research group, which comprised of 208 children aged 11–12 sensitized to felines. In that group monosensitization was found in 67.8% of patients [5].
In the research group the second most frequent feline allergen was Fel d 4. Heightened levels of specific IgE for this feline lipocalin were found in 49.2% of patients. In the study by Bjerg et al. mentioned above, sensitization to Fel d 4 was found in 31.3% of the research group.
It is worth to emphasize, that in our population of adult patients the prevalence of polisensitization was higher than in the study population of Bjerg et al. It is consistent with findings of Asarnoj et al who found, that co sensitization to cat and dog allergen molecules becomes more common when patients are getting older. In their study children were examined during three time points (at 4, 8 and 16 years), and the level of IgE directed against allergen components were measured using microarray technology ImmunoCap ISAC. IgE reactivity to any of the 3 cat allergen molecules tested increased from 9.2% at 4 years up to 21.8% 16 years [8].
Results of The National Health and Nutrition Examination Survey (NHANES) 2005–2006 prove, that, in the USA population, production of IgE is dependent on sociodemographic factors, including gender and age. In NHANES 2005–2006 males seem more likely to have positive sIgE tests as well as elevated levels of sIgEs than females. What is more, inhalant allergen-specific IgEs peaked in childhood and early adulthood, declining in older age. According to authors it may reflect changes in the immune system that accompany aging [9].
In the present study it is worth to emphasize, that although there is a difference in mean value of total IgE in female and male, it is not statistically significant (Table 2). The parameters that are gender dependent are the concentration of IgE specific to Fel d 1 (p = 0.042), with higher values in male, and Can f 1 (p = 0.031), with higher values in female. In our study concentration of IgE specific to cat allergen extract was age dependent (p = 0.032), with higher values in patients >40 than in patients <25 years old. In case of evaluated allergen components the concentrations of IgE were not age dependent, although we feel that further research, on large population of adult patients, is necessary.
Among canine allergens, sensitization to the Can f 1 component was the most frequent—heightened levels of IgE were found in 64.3% of patients sensitized to canine allergen components. Within that group monosensitization was found in 9 patients (32.1%). Sensitization to Can f 5 was found in 52.4% of patients. In the study by Bjerg et al. [5] out of 218 patients (39%) 85 were found to be sensitized to Can f 1, and 102 (46.8%) to Can f 5. Sensitization to Can f 2 occurred as monosensitization extremely rarely, which was confirmed by our findings (1 patient in the research group). The difference in amount of patients sensitized to Can f 1 and Can f 5 in our population may be gathered with multiple factors, including age of the population, different pattern of sensitization or different methodology of the research [5].
Assessing levels of specific IgE to canine and feline allergen components can be helpful in making prognoses about patients who experience allergy reactions after contact with those animals. Some animal allergy components can cross-react both intra- and inter-species.
Information about a specific canine or feline protein which causes the sensitization carries important clinical implications. Relying on knowledge of the component source of the sensitization, theoretically, a potential risk of a cross-allergy, the potential a-typicality of the allergy, or even risks of infertility can be determined. In reality, however, things are, unfortunately, different. The above study points out the importance of allergy co-occurrence as a medical problem, not only among lipocalins or albumins, but also as a co-occurrence of an allergy to proteins belonging to different families. Undoubtedly this factor contributed to an obscuring of the correct clinical view of a case.
It seems that among patients sensitized to felines, with heightened levels of specific IgE to the main allergen Fel d 1, but who do not have specific IgE to other feline components, the risk of a cross-allergy to other fur animals is low, and is mainly related to allergies to rabbits. However, the above results indicate that among 65 patients sensitized to at least one feline component, for 30 (46.2%) it is the only sensitizing feline component, and within that group only 19 (63.3%) patients are not simultaneously sensitized to canines, with 11 (36.7%), despite an isolated feline Fel d 1 sensitization, having symptoms of a concurrent sensitization to some of the canine allergen components.
One of the explanations of this phenomenon may come from an interesting research by Reininger et al. It was the first report demonstrating the presence of an Fel d 1-like allergen in dog dander extracts. It was found that in 25% of Fel d 1-reactive cat-allergic patients (n = 36), more than 50% inhibition of IgE reactivity to dog allergens was achieved with recombinant Fel d 1 [10].
What is more, it seems that the isolated allergy to canine kallikrein is extremely rare. In our research group 42 patients had a sensitization to at least one canine component, 23 of them displayed symptoms of sensitization to Can f 5, and 9 out of these, in turn, out of all canine allergen components had an isolated sensitization only to Can f 5. Only one patient did not have a simultaneous sensitization to any of the feline allergen components.
An important observation seems, that there is a correlation between concentration of specific IgE to canine allergen components, but no such correlation is being observed in case of feline allergen components (Table 3). This phenomenon is not entirely understood. We know, that Can f 1 and Can f 2 have common epitopes and that most of the patients allergic to Can f 2 are co sensitized to Can f 1 [11, 12].
It remains partially unclear why in patients sensitized to fur animals the frequency of co-occurring allergies to a few components is high. Characteristically, this co-occurrence is related to components from different protein families. The high frequency of a co-occurring sensitization to various allergen components that we found in our research group confirms previous findings on this subject.
In a study by Liccardi et al. 900 people, 1/3 out of which had a sensitization to canines and felines and 1/3 were a non-atopic control group, the authors found that in the group of 300 people with sensitization to canines and felines there were significantly more people sensitized also to other fur animals in comparison to the other 300 patients sensitized to other allergens. Moreover, it was found that lack of immediate contact with a given animal (at home or through a hobby) does not exclude an allergy, indicating either a cross-reaction, or an ontogenetic propensity to an allergy to animal hair [13].
A 2015 study by Liccardi et al. conducted a similar analysis, relying on molecular diagnostics. They retrospectively analyzed results of an ISAC test from Allergy Unit, Fondazione Salvatore Maugeri, compiled in the course of 2 years. They divided patients into exactly the same groups as in the study described above (552 patients with a sensitization to canines or felines, 315 sensitized to inhalatory allergens different than canine or feline, and 189 patients with negative ISAC test results). They found that 42.9% of patients with sensitization to canines or felines had heightened levels of IgE to Equ c 1 (equine lipocalin) and Mus m 1 (mouse lipocalin). In other patient groups no heightened levels of specific IgE to Equ c 1 and Mus m 1 were found [14].
In our research group only 30% of the patients displayed monosensitization to 1 canine or feline component. Our results are also tangent with the latest study on the subject conducted by Uriarte et al. [12] which analyzed 159 patients with sensitization to animals. Only 5% of patients in that group were found to have monosensitization to a single allergen component; 86% of patients with sensitization to Fel d 4 were also sensitized to Fel d 1 [15]. In our study sensitization to Fel d 1 was found in 87.5% of patients sensitized to Fel d 4. Out of 10 patients found to have heightened levels of specific IgE to Can f 2, 9 also displayed heightened levels of specific IgE to Fel d 4.
There are a few drawbacks to this study. Although it was generally well conducted, with wide range of diagnostics, including skin prick tests and serum concentration of total IgE, specific IgE and IgE directed against currently available cat and dog allergen components (ImmunoCap), the results are based on only 70 adult patients. This study would benefit from extending the population, but it was limited by relatively high cost of allergen components in ImmunoCap, which were funded with an internal grant, number SLD-4/WL/2015 (Ludwik Rydygier Collegium Medicum in Bydgoszcz, NCU).