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 increased concentration of tumor necrosis factor α (TNF) in the serum an...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2016-12-01
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| Series: | Molecular Medicine |
| Online Access: | http://link.springer.com/article/10.2119/molmed.2015.00206 |
| _version_ | 1819080148309245952 |
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| author | Misa Hirose Anika Kasprick Foteini Beltsiou Katharina Schulze Dieckhoff Franziska Sophie Schulze Unni K J S R L Samavedam Jennifer E Hundt Hendri H Pas Marcel F Jonkman Enno Schmidt Kathrin Kalies Detlef Zillikens Ralf J Ludwig Katja Bieber |
| author_facet | Misa Hirose Anika Kasprick Foteini Beltsiou Katharina Schulze Dieckhoff Franziska Sophie Schulze Unni K J S R L Samavedam Jennifer E Hundt Hendri H Pas Marcel F Jonkman Enno Schmidt Kathrin Kalies Detlef Zillikens Ralf J Ludwig Katja Bieber |
| author_sort | Misa Hirose |
| collection | DOAJ |
| description | 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 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. |
| first_indexed | 2024-12-21T19:40:16Z |
| format | Article |
| id | doaj.art-cad7ed1862314f8189795dfa12ef02bb |
| institution | Directory Open Access Journal |
| issn | 1076-1551 1528-3658 |
| language | English |
| last_indexed | 2024-12-21T19:40:16Z |
| publishDate | 2016-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj.art-cad7ed1862314f8189795dfa12ef02bb2022-12-21T18:52:30ZengBMCMolecular Medicine1076-15511528-36582016-12-0122191892610.2119/molmed.2015.00206Reduced Skin Blistering in Experimental Epidermolysis Bullosa Acquisita After Anti-TNF TreatmentMisa Hirose0Anika Kasprick1Foteini Beltsiou2Katharina Schulze Dieckhoff3Franziska Sophie Schulze4Unni K J S R L Samavedam5Jennifer E Hundt6Hendri H Pas7Marcel F Jonkman8Enno Schmidt9Kathrin Kalies10Detlef Zillikens11Ralf J Ludwig12Katja Bieber13Lübeck Institute of Experimental Dermatology, University of LübeckLübeck Institute of Experimental Dermatology, University of LübeckLübeck Institute of Experimental Dermatology, University of LübeckLübeck Institute of Experimental Dermatology, University of LübeckLübeck Institute of Experimental Dermatology, University of LübeckLübeck Institute of Experimental Dermatology, University of LübeckLübeck Institute of Experimental Dermatology, University of LübeckDepartment of Dermatology, University of GroningenDepartment of Dermatology, University of GroningenLübeck Institute of Experimental Dermatology, University of LübeckInstitute of Anatomy, University of LübeckLübeck Institute of Experimental Dermatology, University of LübeckLübeck Institute of Experimental Dermatology, University of LübeckLübeck Institute of Experimental Dermatology, University of LübeckAbstract 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.http://link.springer.com/article/10.2119/molmed.2015.00206 |
| spellingShingle | Misa Hirose Anika Kasprick Foteini Beltsiou Katharina Schulze Dieckhoff Franziska Sophie Schulze Unni K J S R L Samavedam Jennifer E Hundt Hendri H Pas Marcel F Jonkman Enno Schmidt Kathrin Kalies Detlef Zillikens Ralf J Ludwig Katja Bieber Reduced Skin Blistering in Experimental Epidermolysis Bullosa Acquisita After Anti-TNF Treatment Molecular Medicine |
| title | Reduced Skin Blistering in Experimental Epidermolysis Bullosa Acquisita After Anti-TNF Treatment |
| title_full | Reduced Skin Blistering in Experimental Epidermolysis Bullosa Acquisita After Anti-TNF Treatment |
| title_fullStr | Reduced Skin Blistering in Experimental Epidermolysis Bullosa Acquisita After Anti-TNF Treatment |
| title_full_unstemmed | Reduced Skin Blistering in Experimental Epidermolysis Bullosa Acquisita After Anti-TNF Treatment |
| title_short | Reduced Skin Blistering in Experimental Epidermolysis Bullosa Acquisita After Anti-TNF Treatment |
| title_sort | reduced skin blistering in experimental epidermolysis bullosa acquisita after anti tnf treatment |
| url | http://link.springer.com/article/10.2119/molmed.2015.00206 |
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