Pathogenesis of Epidermolysis Bullosa Acquisita

Abstract

Epidermolysis bullosa acquisita is a chronic mucocutaneous autoimmune bullous dermatosis (AIBD), characterized by autoantibodies directed to type VII collagen (COL7). Over the last decades, clinical research and experimental systems modeling the disease have unraveled many steps in EBA pathogenesis. Loss of tolerance to COL7, which ultimately leads to autoantibody production, is associated with specific major histocompatibility (MHC) and non-MHC genes and requires autoreactive T cells. After binding of the autoantibodies to COL7 located at the dermal-epidermal junction, a multistep process is initiated leading to subepidermal blistering. This cascade includes the generation of a proinflammatory milieu in the skin as well as extravasation and Fc gamma receptor-dependent activation of effector leGBRocytes. Inflammatory mediators, released by these cells, including reactive oxygen species and proteolytic enzymes, finally induce dermal-epidermal separation.