Molecular Allergen-Specific IgE Recognition Profiles and Cumulative Specific IgE Levels Associated with Phenotypes of Cat Allergy

Abstract

Cat allergy is a major trigger factor for respiratory reactions (asthma and rhinitis) in patients with immunoglobulin E (IgE) sensitization. In this study, we used a comprehensive panel of purified cat allergen molecules (rFel d 1, nFel d 2, rFel d 3, rFel d 4, rFel d 7, and rFel d 8) that were obtained by recombinant expression in Escherichia coli or by purification as natural proteins to study possible associations with different phenotypes of cat allergy (i.e., rhinitis, conjunctivitis, asthma, and dermatitis) by analyzing molecular IgE recognition profiles in a representative cohort of clinically well-characterized adult cat allergic subjects (n = 84). IgE levels specific to each of the allergen molecules and to natural cat allergen extract were quantified by ImmunoCAP measurements. Cumulative IgE levels specific to the cat allergen molecules correlated significantly with IgE levels specific to the cat allergen extract, indicating that the panel of allergen molecules resembled IgE epitopes of the natural allergen source. rFel d 1 represented the major cat allergen, which was recognized by 97.2% of cat allergic patients; however, rFel d 3, rFel d 4, and rFel d 7 each showed IgE reactivity in more than 50% of cat allergic patients, indicating the importance of additional allergens in cat allergy. Patients with cat-related skin symptoms showed a trend toward higher IgE levels and/or frequencies of sensitization to each of the tested allergen molecules compared with patients suffering only from rhinitis or asthma, while there were no such differences between patients with rhinitis and asthma. The IgE levels specific to allergen molecules, the IgE levels specific to cat allergen extract, and the IgE levels specific to rFel d 1 were significantly higher in patients with four different symptoms compared with patients with 1-2 symptoms. This difference was more pronounced for the sum of IgE levels specific to the allergen molecules and to cat extract than for IgE levels specific for rFel d 1 alone. Our study indicates that, in addition to rFel d 1, rFel d 3, rFel d 4, and rFel d 7 must be considered as important cat allergens. Furthermore, the cumulative sum of IgE levels specific to cat allergen molecules seems to be a biomarker for identifying patients with complex phenotypes of cat allergy. These findings are important for the diagnosis of IgE sensitization to cats and for the design of allergen-specific immunotherapies for the treatment and prevention of cat allergy.

Keywords: IgE reactivity; allergen molecules; allergy; allergy diagnosis; allergy phenotypes; cat allergens; cat allergy.

Figure 1

Consort diagram of the enrolment of patients.

Figure 2

Correlation between the cumulative sum of Fel d 1–Fel d 8-specific IgE antibody levels and IgE levels to the cat allergen extract. Pearson’s correlation coefficient r = 0.822 (p < 0.01).

Figure 3

Prevalence and magnitude (y-axis: percentage of sensitized patients, measured in kU_A/L, as indicated at the bottom) of IgE sensitization to cat allergen molecules in cat allergic patients (n = 73) with different symptoms (R: rhinitis; A: asthma; D: dermatitis).

Figure 4

IgE levels (y-axis: sensitization, measured in kU_A/L; median IgE levels are indicated by horizontal bars) specific to cat allergen molecules (Fel d 1–Fel d 8) in patients with different symptoms of cat allergy (R: rhinitis; A: asthma; D: dermatitis).

Figure 5

(A) Mean numbers of recognized allergens in patients suffering from 1–2, 3, or 4 cat-related allergic symptoms (asthma, rhinitis, conjunctivitis, and dermatitis); (B) mean levels of IgE (y-axis) specific to the sum of allergen molecules, the cat extract, and Fel d 1 (x-axis) in patients suffering from 1–2, 3, or 4 cat-related allergic symptoms (x-axis). Significant differences were calculated using the Mann–Whitney U test and are indicated for p ≤ 0.05 between the groups.