Abstract
One of the most important functions of the skin besides regulating internal body temperature includes formation of the barrier between the organism and the external environment, hence protecting against pathogen invasion, chemical and physical assaults and unregulated loss of water and solutes. Disruption of the protective barrier is observed clinically in blisters and erosions of the skin that form in autoimmune blistering diseases where the body produces autoantibodies against structural proteins of the epidermis or the epidermal-dermal junction. Although there is no cure for autoimmune skin blistering diseases, immune suppressive therapies currently available offer opportunities for disease management. In cases where no treatment is sought, these disorders can lead to life threatening complications and current research efforts have focused on developing therapies that target autoantibodies which contribute to disease symptoms. This review will outline the involvement of the skin barrier in main skin-specific autoimmune blistering diseases by describing the mechanisms underpinning skin autoimmunity and review current progress in development of novel therapeutic approaches targeting the underlying causes of autoimmune skin blistering diseases.
Highlights
The stratified squamous epithelium of the human epidermis forms a continuous barrier against the external environment and impairments in epithelial adhesions lead to disorders characterized by significant morbidity and/or mortality [1]
Intraepidermal blistering found in pemphigus disorders are caused by autoantibodies targeting cadherin proteins in desmosomes; subtypes pemphigus vulgaris and pemphigus foliaceus are associated with antibodies against desmoglein-3 and−1, respectively
As highlighted in this review, the contribution of the skin barrier to the mechanisms underpinning autoimmunity has greatly improve our understanding of autoimmune blistering diseases (AIBDs)
Summary
The stratified squamous epithelium of the human epidermis forms a continuous barrier against the external environment and impairments in epithelial adhesions lead to disorders characterized by significant morbidity and/or mortality [1]. AIBDs generally occur in the elderly, and often have substantial clinical and immunopathological overlap and polymorphic clinical presentation which can make diagnosis challenging [2] These conditions are driven by humoral and cellular autoimmune responses directed against distinct target antigens and can be classed in three main groups including pemphigoid and pemphigus diseases as well as dermatitis herpetiformis (DH) [3]. Multiple mechanisms of skin barrier disruption and blister formation in AIBDs have been described: in pemphigus disorders steric hindrance (the direct inhibition of protein-protein binding by autoantibodies) and cell signaling events cause desmosomal instability, while complement and inflammatory cell activation mediated through Fc-signaling cause keratinocyte death and blister formation in pemphigoid and epidermolysis bullosa acquisita [7,8,9].
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