Immune mechanism–targeted treatment of experimental epidermolysis bullosa acquisita

Abstract

Epidermolysis bullosa acquisita (EBA) is an autoimmune bullous dermatosis characterized by chronic mucocutaneous blistering caused by autoantibodies directed against type VII collagen. EBA causes a high morbidity and is difficult to treat. Model systems have significantly broadened our understanding of EBA pathogenesis, leading to the identification of numerous therapeutic targets. Of these, so far, a few have been evaluated for their therapeutic potential in preclinical models. In mice, EBA can be induced by transfer of anti-type VII collagen antibodies or by immunization with the protein. The latter model, immunization-induced EBA, is ideal to test drugs for their therapeutic efficacy. Here, mice with already established disease can be treated for prolonged periods. Albeit time consuming, results from immunization-induced EBA will pave the way for clinical application in patients. As the key pathogenic principle, that is, autoantibody-induced, leukocyte-mediated tissue injury and inflammation, is shared by other diseases, these findings may have translational applications beyond EBA.

Keywords:

• anakinra
• animal models
• cell signaling
• cytokines
• epidermolysis bullosa acquisita
• GM-CSF
• p38 MAPK
• PI3K
• treatment

Financial & competing interests disclosure

This research has been supported by funding from the Deutsche Forschungsgemeinschaft as well as research grants from Dompe, Biotest and Suppremol. The author received support for research and/or honoraria from the following companies: Dompe, Biotest AG and Suppremol, which produce/market drugs discussed in this review. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Epidermolysis bullosa acquisita (EBA) is a rare, but prototypical organ-specific autoimmune disease, which is notoriously difficult to treat.

• Animal models have greatly improved the understanding of the disease pathogenesis.

• In addition, EBA animal models have been used to test the activity of ‘established’ treatment, that is, corticosteroids and intravenous immunoglobulin, and novel treatment, that is, cytokine-targeting treatment.

• In the future, this will lead to an improved treatment of patients with EBA, and possibly also other diseases with a similar pathogenesis.

Notes