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.

Sensitization patterns to cat molecular allergens in subjects with allergic sensitization to cat dander

“…Our results also confirm the findings of Grönlund et al that showed that Fel d 1 is a good marker for cat allergy, although, half of the subjects were not monosensitized to Fel d 1 22 . Measurement of minor allergens, in addition to major cat allergen, Fel d 1, could help to identify different phenotypes of cat sensitization and also give additional information about the clinical course 1,35,36 …”

“… 35 A recent study, which studied all registered cat allergens (Fel d 1 to Fel d 8), found that sensitization to Fel d 3, Fel d 4, and Fel d 7 was observed in more than half of the subjects, hence they suggested to appraise these allergens as major/mid‐tier allergens. 36 In our data, nearly 30% of the subjects were sensitized to Fel d 4 and Fel d 7. On the other hand, it has been suggested that revealing allergenic activity might be more valuable than defining the allergens based on only the frequency of IgE recognition for clinical implications.…”

“…To date, allergens are generally classified according to the frequency of IgE‐binding subjects 35 . A recent study, which studied all registered cat allergens (Fel d 1 to Fel d 8), found that sensitization to Fel d 3, Fel d 4, and Fel d 7 was observed in more than half of the subjects, hence they suggested to appraise these allergens as major/mid‐tier allergens 36 . In our data, nearly 30% of the subjects were sensitized to Fel d 4 and Fel d 7.…”

“… 22 Measurement of minor allergens, in addition to major cat allergen, Fel d 1, could help to identify different phenotypes of cat sensitization and also give additional information about the clinical course. 1 , 35 , 36 …”

“…22 Measurement of minor allergens, in addition to major cat allergen, Fel d 1, could help to identify different phenotypes of cat sensitization and also give additional information about the clinical course. 1,35,36 The contribution of this study is to elaborate on the patterns and prevalence of sensitization to specific cat molecular allergens in a representative adult population enriched with asthma sample. Our data show that subjects with cat sensitization do not have homogenous features but show distinct differences in their sensitization profiles.…”