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Patients With Atopic Dermatitis Sensitized to Pet Dander 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

Division 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) : 383-392
doi: 10.18176/jiaci.0737

Background: Immediate and delayed-type hypersensitivity reactions to pet-borne allergens are common in atopic diseases. In atopic dermatitis (AD), controversy surrounds the contribution to the disease of cross-reactivity to self-proteins. Human cystatin A and the cat allergen Fel d 3 belong to the cystatins, an evolutionary conserved protein family. The objective of the present study was to assess crossreactivity between mammalian cystatins and to analyze T-cell responses to cystatin in AD patients sensitized to pet dander.
Methods: cDNA coding for dog cystatin was cloned from dog skin. Sera from 245 patients with IgE-mediated sensitization to cat and dog dander were tested for IgE binding to recombinantly expressed feline, canine, and human cystatin. Of these, 141 were also diagnosed with AD.
Results: Cystatin-specific IgE was detected in 36 patients (14.7%), of whom 19 were considerably affected by AD. Within the AD patients, 9 had measurable IgE against all 3 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 in addition to Fel d 3, the homologous protein from dog might play a role in allergy. Furthermore, human cystatin appears to be capable of driving a type 2 immune response in sensitized AD patients and may therefore be considered a so-called autoallergen, as 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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