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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

1
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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