Mechanisms of blister induction by autoantibodies.
Autoimmune diseases are characterized by defined self-antigens, organ specificity, autoreactive T cells and/or autoantibodies that can transfer disease. Autoimmune blistering diseases are organ-specific autoimmune diseases associated with an immune response directed to structural proteins mediating cell-cell and cell-matrix adhesion in the skin. While both autoreactive T and B cells have been detected and characterized in patients with autoimmune blistering diseases, current evidence generally supports a pathogenic role of autoantibodies for blister formation. The immunopathology associated with blisters induced by autoantibodies relies on several mechanisms of action. Autoantibodies from patients with pemphigus diseases can exert a direct effect just by binding to their target mediated by steric hindrance and/or by triggering the transduction of a signal to the cell. In most subepidermal autoimmune blistering conditions, in addition to the binding to their target antigen, autoantibodies need to interact with factors of the innate immune system, including the complement system and inflammatory cells, in order to induce blisters. Generally, decisive progress has been made in the characterization of the mechanisms of blister formation in autoimmune skin diseases. However, various aspects, including the exact contribution of steric hindrance and signal transduction for pemphigus IgG-induced acantholysis or the fine tuning of the inflammatory cascade triggered by autoantibodies in some subepidermal blistering diseases, still need to be addressed. Understanding the mechanisms by which autoantibodies induce blisters should facilitate the development of more specific therapeutic strategies of autoimmune blistering diseases.
Sitaru
Cassian
C
Department of Dermatology, University of Lübeck, Lübeck, Germany. csitaru@fastmail.fm
Zillikens
Detlef
D
D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001768:Blister / Q000276:immunology*; D006801:Humans; D010392:Pemphigus / Q000276:immunology; D012872:Skin Diseases, Vesiculobullous / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens