Humoral and Cellular Autoreactivity to Epidermal Proteins in Atopic Dermatitis

Abstract

Atopic dermatitis (AD), a chronic relapsing inflammatory disease of the skin, is an important public health concern affecting 10-20 % of children worldwide. The etiology and pathogenesis of AD involve the interplay of genetic and environmental factors, including abnormalities in skin integrity and a skewed immune system usually driven by a Th2 phenotype in childhood with a switch to Th1 in the chronic phase of disease. Children and adults with AD commonly have elevated IgE levels directed to multiple different antigens, including aeroallergens, food allergens, and microbial proteins. IgE targeting self-antigens from epidermal proteins have been detected in up to 91 % of patients, particularly in severe persistent AD. It has been suggested that the occurrence of autoreactivity develops in early childhood. However, it is not clear yet if autoreactive IgEs in patients with AD are pathogenic or just an epiphenomenon. The fact that these autoantibodies are associated with severity and are not present in other allergic or skin diseases favors the pathogenicity of IgE-mediated autoreactivity in AD. In this review, we evaluate the pathogenesis of AD and the emerging role of autoreactivity to various keratinocyte antigens involving both the humoral and cellular components of the immune system.

Flightless I Alters the Inflammatory Response and Autoantibody Profile in an OVA-Induced Atopic Dermatitis Skin-Like Disease

“…Autoimmunity has been increasingly recognized to play part in exacerbating the severity of AD ( 6 , 9 , 12 ) as a consequence of both humoral and cellular and immunity ( 6 ). It is postulated that IFN-γ signaling during AD pathogenesis may promote the development of autoimmunity as IFN-γ overexpressing mice spontaneously develop autoantibodies ( 41 , 42 ) and deletion of the IFN-γ receptor inhibits autoantibody production in lupus-prone mice ( 43 ).…”

Molecular Mechanisms of Cutaneous Inflammatory Disorder: Atopic Dermatitis

“…Additionally, IgE also contributes to autoallergic inflammation in a certain subset of AD patients. Serum IgE autoantibodies to epidermal self-antigens, such as Homo sapiens antigens 1, had a 38.2% prevalence in AD patients of autoreactivity, while patients in the control group showed a 6.4% prevalence [168]. However, the role of IgE in pathogenesis of AD is not major, and previous attempts to inhibit IgE with omalizumab, respectively, showed heterogeneously different therapeutic efficacy in AD patients [169].…”

Molecular aspects of allergens in atopic dermatitis

“…Patients with atopic dermatitis are also frequently sensitized to microbial allergens such as allergens from Malassezia and bacteria including S. aureus and E. coli [6,7,20▪]. Furthermore, they are frequently sensitized to autoallergens [8,9,21]. A recent study showed that patients with atopic dermatitis have not only autoallergen-specific CD4 + but also CD8 + cells [22▪].…”

“…Hence patients with atopic dermatitis are often polysensitized against many different allergens and mount IgE antibodies also against ‘unusual’ allergens such as microbial allergens (e.g. Malassezia, bacteria such Staphylococcus aureus , Escherichia coli ) and also human antigens (i.e., autoallergens) [6–9]. Perturbations of the skin barrier caused by mutations in proteins responsible for the maintenance of the barrier function (e.g.…”