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要旨

Epidermolysis bullosa acquisita (EBA) is a chronic autoimmune blistering skin disease characterized by
autoantibodies against type VII collagen (COL7). Immunization of SJL/J mice with recombinant murine
COL7 results in break of tolerance and skin blisters. Strikingly, despite circulating autoantibodies, the
same genetic background and identical environmental conditions, 20% of mice remain healthy. To
elucidate the regulation of the transition from the presence of autoantibodies to overt autoimmune
disease, we characterized the innate and adaptive immune response of mice that remain healthy after
immunization and compared it to mice that developed skin disease.
Both clinically healthy and diseased SJL/J mice showed circulating autoantibodies and deposition of
complement-fixing IgG2c autoantibodies and C3 at the dermaleepidermal junction. However, only in
diseased animals significant neutrophil infiltration and increase in FcgRIV expression were observed in
the skin. In contrast, the expression of T cell signature cytokines in the T cell zone of the draining lymph
node was comparable between clinically healthy and diseased animals after immunization. Surprisingly,
health was associated with a decreased expression of CD11c, TNFA and KC (CXCL1) in the skin prior to
immunization and could be predicted with a negative predictive value of >80%. Furthermore, mice that
did not develop clinical disease showed a significantly higher richness and distinctly clustered diversity
of their skin microbiota before immunization.
Our data indicate that the decision whether blisters develop in the presence of autoantibodies is
governed in the skin rather than in the lymph node, and that a greater richness of cutaneous bacterial
species appears to be protective.