Details

Autor(en) / Beteiligte

• Koga, Hiroshi
• Recke, Andreas
• Vidarsson, Gestur
• Pas, Hendri H.
• Jonkman, Marcel F.
• Hashimoto, Takashi
• Kasprick, Anika
• Ghorbanalipoor, Saeedeh
• Tenor, Hermann
• Zillikens, Detlef
• Ludwig, Ralf J.

Titel

PDE4 Inhibition as Potential Treatment of Epidermolysis Bullosa Acquisita

Ist Teil von

• Journal of investigative dermatology, 2016-11, Vol.136 (11), p.2211-2220

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Pemphigoid diseases such as epidermolysis bullosa acquisita (EBA) may be difficult to treat. In pemphigoid diseases, mucocutaneous blistering is caused by autoantibodies to hemidesmosomal antigens; in EBA the autoantigen is type VII collagen. Despite growing insights into pemphigoid disease pathogenesis, corticosteroids are still a mainstay of treatment. In experimental EBA, myeloid cell activation is a key event leading to blistering. Activation of these cells depends on phosphodiesterase (PDE) 4. We therefore evaluated the potential for PDE4 inhibition in EBA: PDE4 was highly expressed in inflammatory cells and in the epidermis of patients compared with healthy skin samples. PDE4 inhibitors rolipram, roflumilast, and roflumilast N-oxide prevented the release of immune complex-induced reactive oxygen species from polymorphonuclear leukocytes and separation of the dermal-epidermal junction of skin incubated with antibodies to collagen type VII and polymorphonuclear leukocytes. The PDE4 inhibitors also impaired CD62L shedding and decreased CD11b expression on immune complex-stimulated polymorphonuclear leukocytes. For in vivo validation, experimental EBA was induced in mice by transfer of anti-collagen type VII IgG or immunization with collagen type VII. Roflumilast dose-dependently reduced blistering in antibody transfer-induced EBA and also hindered disease progression in immunization-induced EBA. PDE4 inhibition emerges as a new treatment modality for EBA and possibly other neutrophil-driven pemphigoid diseases.