Upcoming therapeutic targets in cutaneous lupus erythematous

ABSTRACT

Novel insights into molecular mechanisms have altered our understanding of the pathogenesis of autoimmune skin disorders. Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease characterized by auto-aggressive skin inflammation which histologically presents with interface dermatitis. This inflammation is driven by interferon (IFN)-regulated proinflammatory cytokines that orchestrate the B- and T-cell mediated lesional inflammation. During the last years, therapeutic strategies have focused on these players: biologicals targeting type I IFNs and their receptors as well as anti-B-cell drugs have been investigated in clinical trials with variable success. Very recently, CLE gene expression analyses revealed lesional activation of several pathways of the immune system, thus providing potential new therapeutic targets. In this article, we review the current knowledge concerning pathways and key mediators involved in the pathogenesis of cutaneous lupus erythematosus (including TLR-dependent and TLR–independent immune activation, NfkB, TBK1, PI3K, MAPK, JAK/STAT-pathway) and their inhibitors (e.g. chloroquine, bufalin, duvelisib, rapamycin, R788, KN-93, amlexanox, tofacitinib, ruxolitinib, baricitinib), and discuss emerging strategies for the treatment of CLE and related diseases.

KEYWORDS:

• Lupus
• skin
• kinase
• interferon
• TLR
• pathway

Acknowledgment

The authors thank Nadine van Holt (University Hospital Bonn) for her most valuable support in preparation of the manuscript and many helpful comments.

Financial and competing interests disclosure

J Wenzel has received financial support for research, clinical studies and/or lectures from Novartis, GlaxoSmithKline, and Medac. The authors have 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.