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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.  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.

Patients With Atopic Dermatitis Sensitized to Pet Dander Mount IgE and T-Cell Responses to Mammalian Cystatins, Including the Human Self-Protein