IgE autoantibodies and autoreactive T cells and their role in children and adults with atopic dermatitis

Abstract

The pathophysiology of atopic dermatitis (AD) is highly complex and understanding of disease endotypes may improve disease management. Immunoglobulins E (IgE) against human skin epitopes (IgE autoantibodies) are thought to play a role in disease progression and prolongation. These antibodies have been described in patients with severe and chronic AD, suggesting a progression from allergic inflammation to severe autoimmune processes against the skin. This review provides a summary of the current knowledge and gaps on IgE autoreactivity and self-reactive T cells in children and adults with AD based on a systematic search. Currently, the clinical relevance and the pathomechanism of IgE autoantibodies in AD needs to be further investigated. Additionally, it is unknown whether the presence of IgE autoantibodies in patients with AD is an epiphenomenon or a disease endotype. However, increased knowledge on the clinical relevance and the pathophysiologic role of IgE autoantibodies and self-reactive T cells in AD can have consequences for diagnosis and treatment. Responses to the current available treatments can be used for better understanding of the pathways and may shed new lights on the treatment options for patients with AD and autoreactivity against skin epitopes. To conclude, IgE autoantibodies and self-reactive T cells can contribute to the pathophysiology of AD based on the body of evidence in literature. However, many questions remain open. Future studies on autoreactivity in AD should especially focus on the clinical relevance, the contribution to the disease progression and chronicity on cellular level, the onset and therapeutic strategies.

Keywords: Atopic dermatitis; Autoallergens; Autoreactive T cells; Autoreactivity; IgE autoantibodies.

Fig. 1

Flow diagram of the systematic search

Fig. 2

Molecular mimicry can lead to IgE antibody production against self-antigens. An impaired barrier function facilitates access to environmental allergens and pathogens resulting in allergic sensitization and specific IgE antibody production. In the case of structural homologies of the epitopes (molecular mimicry), this can result in cross reactivity between exogenous antigens and self-antigens. DC dendritic cell, Th2 T helper 2 lymphocytes, IgE immunoglobulin E, IL-4 interleukin-4

Fig. 3

Hypothetic cellular pathways and targets of autoreactivity in atopic dermatitis. Skin damage can lead to release of self-peptides resulting in allergic sensitization to autoantigens via antigen presentation by dendritic cells (DC) to naïve T cells and class switch of B cells. Mast cells sensitized with IgE autoantibodies can directly interfere with the self-peptides that are released following skin damage resulting in histamine release. T cells with low binding affinity to self-peptides may escape selection and depletion in the thymus. Possibly, this population of cells may also be attracted to the skin where they are exposed to the self-peptides of the damaged skin. Cytokines (IL-4 and IFN-γ) produced by T-cells, and histamine by MC can directly exacerbate the skin lesion. Additionally, neurons in the skin can bind histamine and IL-31 specifically to the histamine 1 receptor (H1R) and IL-31 receptor (IL-31R) which results in itch and may lead to the chronicity of the impaired barrier function. Th2 T helper lymphocyte, EO eosinophils, ILC2 innate lymphoid cell, IgE immunoglobulin E, IL interleukin, IFN-γ Interferon gamma, TSLP thymic stromal lymphopoietin