title: Reduced skin blistering in experimental epidermolysis bullosa acquisita after anti-TNF treatment.
abstract: 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 an increased concentration of tumor necrosis factor alpha (TNF) in the serum and blister fluid of patients with subepidermal AIBDs. Furthermore, successful anti-TNF treatment has been reported for individual patients with AIBDs. 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 PCR and immunohistochemistry. To investigate if 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 receiving either of these two 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 to controls. Furthermore, etanercept treatment significantly reduced the disease progression in immunization-induced EBA. In conclusion, the 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 the 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.
authors.affiliation: Lübeck Institute of Experimental Dermatology, University of Lübeck, Germany.
authors.forename: Misa
authors.initials: M
authors.lastname: Hirose
authors.affiliation: Lübeck Institute of Experimental Dermatology, University of Lübeck, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Kasprick
authors.affiliation: Lübeck Institute of Experimental Dermatology, University of Lübeck, Germany.
authors.forename: Foteini
authors.initials: F
authors.lastname: Beltsiou
authors.affiliation: Lübeck Institute of Experimental Dermatology, University of Lübeck, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Dieckhoff Schulze
authors.affiliation: Lübeck Institute of Experimental Dermatology, University of Lübeck, Germany.
authors.forename: Franziska Sophine
authors.initials: FS
authors.lastname: Schulze
authors.affiliation: Lübeck Institute of Experimental Dermatology, University of Lübeck, Germany.
authors.forename: Unni Kjsrl
authors.initials: UK
authors.lastname: Samavedam
authors.affiliation: Lübeck Institute of Experimental Dermatology, University of Lübeck, Germany.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Hundt
authors.affiliation: Department of Dermatology, University of Groningen, Groningen, the Netherlands.
authors.forename: Hendri H
authors.initials: HH
authors.lastname: Pas
authors.affiliation: Department of Dermatology, University of Groningen, Groningen, the Netherlands.
authors.forename: Marcel F
authors.initials: MF
authors.lastname: Jonkman
authors.affiliation: Lübeck Institute of Experimental Dermatology, University of Lübeck, Germany.
authors.forename: Enno
authors.initials: E
authors.lastname: Schmidt
authors.affiliation: Institute of Anatomy, University of Lübeck, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kalies
authors.affiliation: Lübeck Institute of Experimental Dermatology, University of Lübeck, Germany.|Department of Dermatology, Allergology and Venereology, University of Lübeck, Lübeck, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Zillikens
authors.affiliation: Lübeck Institute of Experimental Dermatology, University of Lübeck, Germany.
authors.forename: Ralf J
authors.initials: RJ
authors.lastname: Ludwig
authors.affiliation: Lübeck Institute of Experimental Dermatology, University of Lübeck, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Bieber
keywords: TNF-alpha; chemokines; dermatology; immunology; inflammation