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.

EAACI Biologicals Guidelines—dupilumab for children and adults with moderate‐to‐severe atopic dermatitis

“…[6][7][8][9][10] 1.1.2 | Atopic dermatitis phenotypes and endotypes-practical implications for management AD has highly complex pathophysiology and heterogeneous clinical presentations, which are illustrated by different features such as age of disease onset, variable IgE sensitisations to allergens, spectrum of severity, potential of IgE autoreactivity and co-morbidities (asthma, rhinitis, food allergy, infections and others). [11][12][13][14] Improved understanding of the contribution of immune-inflammatory mechanisms in AD has encouraged the development of biologicals and small molecules specifically targeting the key pathogenetic mechanisms. The use of targeted treatment is facilitated by the concept of phenotypes (visible properties) and endotypes (pathogenetic mechanisms).…”

“…19,[32][33][34][35][36] The link between the endotype and the phenotype is facilitated by biomarkers. 12,14,[37][38][39][40] Stratified medicine is the endotype/biomarker-driven approach that classifies individuals into subpopulations differing in their susceptibility to a particular disease or their response to a particular treatment. It is facilitated by a subgroup of biomarkers serving to stage diseases based on prognosis or underlying biological mechanism, thus enabling the concept of enrichment.…”

“…AD has highly complex pathophysiology and heterogeneous clinical presentations, which are illustrated by different features such as age of disease onset, variable IgE sensitisations to allergens, spectrum of severity, potential of IgE autoreactivity and co‐morbidities (asthma, rhinitis, food allergy, infections and others) 11‐14 …”

“…The link between the endotype and the phenotype is facilitated by biomarkers 12,14,37‐40 . Stratified medicine is the endotype/biomarker‐driven approach that classifies individuals into subpopulations differing in their susceptibility to a particular disease or their response to a particular treatment.…”

The emerging role of autoreactive antibodies in inflammatory skin diseases

“…Self‐reactive antibodies have been identified in various chronic inflammatory skin diseases, such as chronic spontaneous urticarial, 1 atopic dermatitis, 2,3 systemic lupus erythematosus 4 and autoimmune bullous diseases 5 . The presence of these autoreactive antibodies against epitopes in the skin is assumed to contribute to the disease pathophysiology.…”