Serum IgE Autoantibodies Target Keratinocytes in Patients with Atopic Dermatitis

Abstract

Previous studies have shown that sera of patients with severe atopic dermatitis (AD) contain IgE specific for self-proteins, supporting the hypothesis of autoreactivity as a pathogenic factor in AD. In this study, we screened a large panel of AD patients (n=192) by western blotting (WB) for IgE reactivity not only against the human epithelial cell line A431 but also against primary keratinocytes (KCs). To investigate autoantigenic cell structures in detail, normal human skin and primary KCs were incubated with sera from both WB-reactive patients and, for control purposes, healthy individuals, and analyzed by immunohistology, confocal laser microscopy, and flow cytometry. Our analysis revealed that 28% of AD patients, but not healthy individuals, display serum IgE autoreactivity by WB analysis. The individual IgE reaction patterns of the sera pointed to the existence of unique as well as common specificities against epidermal or A431-derived proteins. Immunostainings identified cytoplasmic and, occasionally, also cell membrane-associated moieties as targets for autoreactive IgE antibodies. Interestingly, in certain autoreactive patients, the surface-staining pattern was accentuated at cellular contact sites. We conclude that IgE autoreactivity is common, particularly among severe AD patients, and that non-transformed primary cells are needed for characterization of the entire spectrum of IgE-defined autoantigens.

Therapeutic Implications of a Barrier-based Pathogenesis of Atopic Dermatitis

“…The basis for these negative effects of IL-4 includes: 1) inhibition of ceramide (Cer) synthesis 81 , providing yet another mechanism accounting for decreased Cer in AD; 2) inhibition of keratinocyte differentiation-linked proteins, most notably loricrin and FLG 27 ; and 3) decreased desmoglein 3 expression, which would further compromise SC integrity 80,81 . In a further 'vicious cycle,' serum IgE from AD patients auto-reacts against a variety of keratinocyte antigens 82 . Together, these observations provide acquired mechanisms that could further compromise barrier function in AD 27 .…”

Eosinophilic Granulomatosis with Polyangiitis Demonstrating IgE-immune Complexes and the Possible Involvement of IgE Autoantibodies

“…IgE autoantibodies for atopic dermatitis and bullous pemphigoid has been previously demonstrated (7,8). These IgE autoantibodies play important roles in each disease.…”

Justification for IgE as a therapeutic target in chronic spontaneous urticaria

“…(40). Anti-dsDNA, anti-thyroglobulin, and anti-thyroid peroxidase IgE autoantibodies have been described in patients with CSU (41)(42)(43)(44). Anti-dsDNA IgE has been shown to activate basophils (45) and it has been proposed that mast cell activation through binding of autoantigens released from damaged skin to IgE on FceRI would be a central mechanism in CSU (1).…”