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. 2023 Nov 24;24(23):16729.
doi: 10.3390/ijms242316729.

Allergenic Activity of Individual Cat Allergen Molecules

Daria Trifonova  1   2 , Mirela Curin  1 , Ksenja Riabova  2 , Antonina Karsonova  2 , Walter Keller  3 , Hans Grönlund  4 , Ulrika Käck  5 , Jon R Konradsen  6   7 , Marianne van Hage  8 , Alexander Karaulov  2 , Rudolf Valenta  1   2   9
Affiliations

Allergenic Activity of Individual Cat Allergen Molecules

Daria Trifonova et al. Int J Mol Sci. .

Abstract

More than 10% of the world's population suffers from an immunoglobulin E (IgE)-mediated allergy to cats which is accompanied mainly by respiratory symptoms such as rhinitis and asthma. Several cat allergen molecules have been identified, but their allergenic activity has not been investigated in depth. Purified cat allergen molecules (Fel d 1, Fel d 2, Fel d 3, Fel d 4, Fel d 6, Fel d 7 and Fel d 8) were characterized via mass spectrometry and circular dichroism spectroscopy regarding their molecular mass and fold, respectively. Cat-allergen-specific IgE levels were quantified via ImmunoCAP measurements in IgE-sensitized subjects with (n = 37) and without (n = 20) respiratory symptoms related to cat exposure. The allergenic activity of the cat allergens was investigated by loading patients' IgE onto rat basophils expressing the human FcεRI receptor and studying the ability of different allergen concentrations to induce β-hexosaminidase release. Purified and folded cat allergens with correct masses were obtained. Cat-allergen-specific IgE levels were much higher in patients with a respiratory allergy than in patients without a respiratory allergy. Fel d 1, Fel d 2, Fel d 4 and Fel d 7 bound the highest levels of specific IgE and already-induced basophil degranulation at hundred-fold-lower concentrations than the other allergens. Fel d 1, Fel d 4 and Fel d 7 were recognized by more than 65% of patients with a respiratory allergy, whereas Fel d 2 was recognized by only 30%. Therefore, in addition to the major cat allergen Fel d 1, Fel d 4 and Fel d 7 should also be considered to be important allergens for the diagnosis and specific immunotherapy of cat allergy.

Keywords: IgE reactivity; allergenic activity; allergy; basophil activation test; cat allergen molecule; cat allergy.

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Conflict of interest statement

R.V. received research grants from HiPP GmbH & Co., Vertrieb KG, Pfaffenhofen, Germany; Worg Pharmaceuticals, Hangzhou, China; HVD Biotech, Vienna, Austria; and Viravaxx, Vienna, Austria. He serves as a consultant for Viravaxx and Worg. D.T., M.C., K.R., A.K. (Antonina Karsonova), M.v.H., A.K. (Alexander Karaulov) and R.V. are authors of the patent application “Vaccine for treating allergies” application number: PCT/CN2022/130414, reference: P20222370. The other authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; or in the decision to publish the results. The authors with Russian affiliation declare that they have prepared the article in their “personal capacity” and/or that they are employed at an academic/research institution where research or education is the primary function of the entity.

Figures

Figure 1
Figure 1
CD spectra of recombinant cat allergens. The mean residue ellipticities (Θ) (y-axes) are shown at given wavelengths (x-axes) for the individual recombinant cat allergens rFel d 1, rFel d 3, rFel d 4, rFel d 7 and rFel d 8.
Figure 2
Figure 2
IgE levels to individual recombinant cat allergens and cat hair extract, determined by ImmunoCAP. Specific IgE levels (kUA/L, y-axis) to cat allergens and a cat extract (x-axis), determined for a Swedish population with reactivity to cat extract, are displayed as scatter plots (A). The dotted line represents the cut-off value of 0.1 kUA/L. Mean IgE levels are presented as horizontal lines. Statistical significance and percentages of IgE-positive sera for the individual allergens are displayed above the plots (significance considered as a p-value < 0.05 and indicated by stars; ns, not significant). (B) Correlations between IgE to cat allergen extract (x-axes) and Fel d 1 (y-axes), (C) cat allergen extract and the sum of IgE against Fel d 1-Fel d 8 and (D) between cat-extract-specific IgE and the sum of Fel d 1, Fel d 4 and Fel d 7-specific IgE are displayed as scatterplots. The correlation coefficients and levels of significance (p-values) are shown in the upper right corner of the graphs.
Figure 3
Figure 3
Comparison of the allergenic activity of individual cat allergen molecules. RBL cells were loaded with serum IgE from 17 cat-sensitized children (#4, 5, 7, 10, 12, 13, 16, 23, 24, 26, 27, 29, 34, 36, 51, 57 and 56) and then stimulated with increasing allergen concentrations (0.1 to 1000 ng/mL; x-axes; Fel d 1, Fel d 2, Fel d 3, Fel d 4, Fel d 6, Fel d 7 and Fel d 8, according to color code). Patients were grouped into those showing basophil activation mainly to Fel d 1 exposure (A), whereas (B) shows patients also showing mediator release to other cat allergens. β-hexosaminidase releases are expressed as percentages of total mediator contents (y-axes). The horizontal cut-off line indicates the percentage of spontaneous β-hexosaminidase release without the addition of allergens. The corresponding IgE levels (kUA/L) of the individual cat allergen molecules are shown above the graphs.
Figure 3
Figure 3
Comparison of the allergenic activity of individual cat allergen molecules. RBL cells were loaded with serum IgE from 17 cat-sensitized children (#4, 5, 7, 10, 12, 13, 16, 23, 24, 26, 27, 29, 34, 36, 51, 57 and 56) and then stimulated with increasing allergen concentrations (0.1 to 1000 ng/mL; x-axes; Fel d 1, Fel d 2, Fel d 3, Fel d 4, Fel d 6, Fel d 7 and Fel d 8, according to color code). Patients were grouped into those showing basophil activation mainly to Fel d 1 exposure (A), whereas (B) shows patients also showing mediator release to other cat allergens. β-hexosaminidase releases are expressed as percentages of total mediator contents (y-axes). The horizontal cut-off line indicates the percentage of spontaneous β-hexosaminidase release without the addition of allergens. The corresponding IgE levels (kUA/L) of the individual cat allergen molecules are shown above the graphs.
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