Missing regulatory T cell (Treg) control contributes to the development of different autoimmune diseases. Scurfy mice have a missense mutation in the transcription factor Foxp3 which leads to dysfunctional Tregs. Previously, we have shown that scurfy mice develop high titers of autoantibodies with reactivity to structural proteins in the skin. Furthermore, the development of a pathogenic autoantibody that targets BP230 and induces a bullous pemphigoid-like phenotype indicates the progression of autoimmune blistering diseases (AIBD) in the absence of functional Tregs. Given the polyclonal nature of autoimmune disease in scurfy mice, hybridomas of spontaneously activated B cells were screened for antibodies against other potential pathogenic target antigens. We found a murine IgG1 autoantibody (H510) which is pathogenic in vivo as it induces subepidermal blisters in neonatal mice and binds to the blister floor on murine salt-split skin in indirect immunofluorescence (IIF). After we excluded that H510 binds to laminin-332, we identified type VII collagen (Col7) as a potential autoantigen. Western blot analysis and IIF staining using skin from Col7 knock-out mice revealed Col7 as the target antigen of H510. Using western blot analysis, we further mapped the antigenic epitope to the murine von-Willebrand-factor-A-like domain 2 of Col7. In summary, we here present a recently identified, pathogenic autoantibody spontaneously developed in the absence of functional Tregs with reactivity against Col7 as a useful model for the induction of Epidermolysis bullosa acquisita in mice.

ESDR006 - Pathogenic autoantibody derived from Treg-deficient scurfy mice targets Type VII Collagen and induces Epidermolysis bullosa acquisita-like blistering disease

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING