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

Abstract

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.

Sensitization to molecular dog allergens in an adult population: Results from the West Sweden Asthma Study

“…Nevertheless, these results might also indicate a need for the identification of new molecular allergens to which current non‐sensitized individuals might be sensitized 16,24 . Two new dog allergen molecules, Can f 7 and Can f 8, have been recently identified and added to the WHO/IUIS Allergen Nomenclature database, after the analyses in our study and the study by Käck and colleagues were performed 18,39,40 . Another explanation could be the presence of α‐Gal in cat and dog dander extracts 41 .…”

“… 16 , 24 Two new dog allergen molecules, Can f 7 and Can f 8, have been recently identified and added to the WHO/IUIS Allergen Nomenclature database, after the analyses in our study and the study by Käck and colleagues were performed. 18 , 39 , 40 Another explanation could be the presence of α‐Gal in cat and dog dander extracts. 41 Kiewiet et al, 42 in a recent study of patients with α‐Gal syndrome, found a high frequency of sensitization to both dog and cat extracts but a low frequency of genuine cat and dog sensitization using CRD.…”

Autoreactive IgE: Pathogenic role and therapeutic target in autoimmune diseases

“…These autoantigens may then be processed by antigen presenting cells and presented to lymphocytes resulting in the production of IgG and/or IgE AAb by plasma cells 105 . IgE‐mediated autoimmunity in AD may also be caused by molecular mimicry due to cross‐reactive peptides between environmental antigens or skin microbiome and self‐antigens 91,106–108 . In addition, skin residing CD8 + cytotoxic T cells with intermediate affinity to self‐peptides may contribute to skin damage, and unconventional γδ T cells may also accumulate in the skin 109,110 .…”

“…105 IgE-mediated autoimmunity in AD may also be caused by molecular mimicry due to cross-reactive peptides between environmental antigens or skin microbiome and self-antigens. 91,[106][107][108] In addition, skin residing CD8 + cytotoxic T cells with intermediate affinity to self-peptides may contribute to skin damage, and unconventional γδ T cells may also accumulate in the skin. 109,110 Finally, an extraordinary unspecific activation of the T and B cells might also underlie the response due to the conditions of an ongoing inflammation.…”

Autoreactive IgE: pathogenic role and therapeutic target in autoimmune diseases

“…These autoantigens may then be processed by antigen presenting cells and presented to lymphocytes resulting in the production of IgG and/or IgE AAb by plasma cells 103 . IgE-mediated autoimmunity in AD may also be caused by molecular mimicry due to cross-reactive peptides between environmental antigens or skin microbiome and self-antigens 89,[104][105][106] . In addition, skin residing CD8 + cytotoxic T cells with intermediate affinity to selfpeptides may contribute to skin damage, and unconventional γδ T cells may also accumulate in the skin 107,108 .…”