Reduced Skin Blistering in Experimental Epidermolysis Bullosa Acquisita After Anti-TNF Treatment

Misa Hirose, Anika Kasprick, Foteini Beltsiou, Katharina Schulze Dieckhoff, Franziska Sophie Schulze, Unni KJSRL Samavedam, Jennifer E Hundt, Hendri H Pas, Marcel F Jonkman, Enno Schmidt, Kathrin Kalies, Detlef Zillikens, Ralf J Ludwig, and Katja Bieber
Epidermolysis bullosa acquisita (EBA) is a difficult-to-treat subepidermal autoimmune blistering skin disease (AIBD) with circulating and tissue-bound anti–type VII collagen antibodies. Different reports have indicated increased concentration of tumor necrosis factor α (TNF) in the serum and blister fluid of patients with subepidermal AIBD. Furthermore, successful anti-TNF treatment has been reported for individual patients with AIBD. Here we show that in mice, induction of experimental EBA by repeated injections of rabbit anti-mouse type VII collagen antibodies led to increased expression of TNF in skin, as determined by real-time polymerase chain reaction (PCR) and immunohistochemistry. To investigate whether the increased TNF expression is of functional relevance in experimental EBA, we inhibited TNF function using the soluble TNF receptor fusion protein etanercept (Enbrel) or a monoclonal antibody to murine TNF. Interestingly, mice that received either of these treatments showed significantly milder disease progression than controls. In addition, immunohistochemical staining demonstrated reduced numbers of macrophages in lesional skin in mice treated with TNF inhibitors compared with controls. Furthermore, etanercept treatment significantly reduced disease progression in immunization-induced EBA. In conclusion, increased expression of TNF in experimental EBA is of functional relevance, as both the prophylactic blockade of TNF and the therapeutic use of etanercept impaired induction and progression of experimental EBA. Thus, TNF is likely to serve as a new therapeutic target for EBA and AIBDs with a similar pathogenesis.
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Date Published
December 20, 2016
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Hirose, Kasprick, Beltsiou, Dieckhoff, Schulze, Samavedam, Hundt, Pas, Jonkman, Schmidt, Kalies, Zillikens, Ludwig, Bieber, Epidermolysis bullosa acquisita, EBA, skin blistering, Tumor necrosis factor α, TNF, immune-mediated inflammatory disease, immunology, inflammation, dermatology, TNF-alpha
Article Type
Research Article