362 Treg deficiency leads to development of BP230-autoantibody mediated autoimmune blistering disease

Abstract

Regulatory T cells (Treg) are crucial for the prevention of autoimmune diseases. Scurfy mice lack functional Treg and consequently there is no suppression of auto-reactive T cells in the periphery. A missense mutation of the foxp3 gene leads to loss of function of Treg and T cell-mediated inflammation in different organs of scurfy mice. Beside skin inflammation, we detected autoantibodies specific for different structural skin proteins (BP180, Laminin 332 and p200), which are known autoantigens of different autoimmune blistering diseases (AIBD). In addition to autoantibodies in sera and skin, some scurfy mice also showed blister formation in different areas of skin. We isolated monoclonal autoantibodies from scurfy mice by hybridoma generation and one of the monoclonal antibodies was pathogenic in vivo as demonstrated by injection into neonatal mice: The majority of injected mice, showed subepidermal blisters and the antibody was detectable in the sera and in the skin by immunofluorescence staining. Next we identified bullous pemphigoid antigen-230 (BP230) as the target antigen by immunoprecipitation followed by Maldi-TOF. In summary we show that BP230 autoantibodies i) develop in the absence of functional Treg and ii) can induce blister formation in mice.