Keratinocyte-associated autoantigen

Keratinocyte-associated autoantigens are a group of structural proteins expressed by keratinocytes in the epidermis that become the primary targets of the immune system in various autoimmune blistering diseases. These antigens include desmosomal proteins such as desmoglein 1 and 3, which are essential for maintaining cell-cell adhesion, and hemidesmosomal proteins like BP180 (type XVII collagen) and BP230, which anchor the epidermis to the underlying basement membrane. In diseases such as pemphigus and bullous pemphigoid, the production of pathogenic autoantibodies against these proteins disrupts their adhesive function, leading to the formation of painful blisters and erosions on the skin and mucous membranes. While traditional treatments rely on broad immunosuppression to reduce autoantibody production, modern therapeutic strategies are increasingly focused on antigen-specific approaches. For example, Chimeric Autoantibody Receptor (CAAR) T cells, such as DSG3-CAART, are being developed to selectively target and eliminate the specific B cell clones that produce autoantibodies against these keratinocyte antigens. This shift toward precision medicine aims to provide effective disease control while minimizing the systemic side effects associated with conventional immunosuppressants.

Other names

Epidermal autoantigenKeratinocyte-derived autoantigenSkin autoantigenAutoimmune bullous disease autoantigen

Therapeutic strategies include the depletion of B cells producing autoantibodies (e.g., via CD20 targeting), the inhibition of the neonatal Fc receptor (FcRn) to accelerate the clearance of pathogenic autoantibodies, and the use of Chimeric Autoantibody Receptor (CAAR) T cells to specifically eliminate autoreactive B cell clones.