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Atopic Dermatitis Patients with Pet Dander Sensitization Mount IgE and T cell Responses to Mammalian Cystatins Including the Human Self-Protein

Roesner LM1, Swiontek K2, Lentz D2, Begemann G1, Kienlin P1, Hentges F3, Ollert M2,4, Werfel T1, Hilger C2

1Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School (MHH), Hannover, Germany
2Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
3Immunology Allergology Unit, Centre Hospitalier, Luxembourg, Luxembourg
4Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis, University of Southern Denmark, Odense, Denmark

J Investig Allergol Clin Immunol 2022; Vol. 32(5)
doi: 10.18176/jiaci.0737

Background: Immediate as well as delayed-type hypersensitivity immune reactions to pet-borne allergens are commonly observed in atopic diseases. Further on in atopic dermatitis (AD), cross-reactivity to self-proteins is discussed to contribute to the disease. Human cystatin A and the cat allergen Fel d 3 belong to the cystatin family, an evolutionary conserved protein family. The objective of the present study was to assess cross-reactivity between mammalian cystatins and to analyze T cell responses to cystatin in AD patients sensitized to pet dander.
Material and methods: cDNA coding for dog cystatin was cloned from dog skin. Sera of 245 patients with IgE-sensitization to cat and dog dander were tested for IgE-binding to recombinantly expressed feline, canine, and human cystatin, respectively. Of these, 141 were also diagnosed for AD.
Results: Cystatin-specific IgE was detected in 14.7 %(36) of patients, of which 19 suffered from AD. Within the AD patients, 9 carried measurable IgE against all three cystatins. Cystatin-sensitized AD patients did not differ from non-cystatin sensitized patients in terms of disease severity, age or total IgE levels. T cell cytokine measurements showed elevated IL-4 levels after stimulation with feline and human cystatin.
Conclusion: The humoral response suggests that next to Fel d3 also the homologous protein from dog might play a role in allergy. Further on, the human cystatin appears to be capable of driving a type2 immune response in sensitized AD patients and may therefore be considered a so-called autoallergen, as it has been proposed for other evolutionary conserved proteins.

Key words: Allergy, Sensitization, Atopic dermatitis, Pet, IgE, T cell, Cross-reactivity, Autoallergy, Autoreactivity, Fel d 3, Can f 8, Cystatin, Cytokine

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