Dapsone Suppresses Disease in Preclinical Murine Models of Pemphigoid Diseases

Sripriya Murthy, Paul Schilf, Sabrina Patzelt, Markus Thieme, Mareike Becker, Lasse Kröger, Tabea Bremer, Aleksandra Derenda-Hell, Lea Knebel, Francesca Fagiani, Saleh M. Ibrahim, Enno Schmidt, Detlef Zillikens, Christian D. Sadik*

*Corresponding author for this work

Abstract

Epidermolysis bullosa acquisita and mucous membrane pemphigoid are autoimmune blistering diseases characterized by mucocutaneous blisters elicited by an autoantibody-mediated immune response against specific proteins of the epidermal basement membrane. The antibiotic dapsone is frequently used to treat both diseases, but its therapeutic effectiveness is uncertain, and its mode of action in these diseases is largely unknown. We evaluated the effect of dapsone in antibody transfer mouse models of epidermolysis bullosa acquisita and mucous membrane pemphigoid, which do not allow the drawing of conclusions on clinical treatment regimens but can be instrumental to partially uncover the mode(s) of action of dapsone in these diseases. Dapsone significantly mitigated inflammation in both models, reducing the recruitment of neutrophils into the skin and disrupting their release of leukotriene B4 (LTB4) and ROS in response to immune complexes. LTB4 has been implicated in numerous diseases, but effective LTB4 inhibitors for clinical use are not available. Our findings indicate that the mode of action of dapsone in these models may be based on the inhibition of LTB4 and ROS release from neutrophils. Moreover, they encourage testing the use of dapsone as an effective, albeit nonspecific, inhibitor of LTB4 biosynthesis in other LTB4-driven diseases.

Original languageEnglish
JournalJournal of Investigative Dermatology
Volume141
Issue number11
Pages (from-to)2587-2595.e2
ISSN0022-202X
DOIs
Publication statusPublished - 11.2021

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)
  • Centers: Center for Research on Inflammation of the Skin (CRIS)

DFG Research Classification Scheme

  • 2.21-05 Immunology
  • 2.22-19 Dermatology

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  • EXC 2167: Precision Medicine in Chronic Inflammation (PMI)

    Schreiber, S. (Speaker, Coordinator), Baines, J. F. (Project Staff), Bosch, T. C. G. (Project Staff), Buyx, A. (Project Staff), Erdmann, J. (Project Staff), Franke, A. (Project Staff), Huber, R. (Project Staff), Klein, C. (Project Staff), Köhl, J. (Project Staff), König, I. R. (Project Staff), Lange, C. (Project Staff), Laudes, M. (Project Staff), Lieb, W. (Project Staff), Ludwig, R. (Project Staff), Nebel, A. (Project Staff), Niemann, S. (Project Staff), Rabe, K. F. (Project Staff), Riemekasten, G. (Project Staff), Rose-John, S. (Project Staff), Rosenstiel, P. C. (Project Staff), Schulenburg, H. (Project Staff), Schwarz, K. (Project Staff), Traulsen, A. (Project Staff), Weidinger, S. (Project Staff) & Zillikens, D. (Project Staff)

    01.01.19 → …

    Project: DFG ProjectsDFG Cluster of Excellence

  • CRU 303: Pemphigoid Diseases - Molecular Pathways and their Therapeutic Potential

    Sadik, C. (Speaker, Coordinator), Zillikens, D. (Speaker, Coordinator), Ibrahim, S. (Principal Investigator (PI)), Baines, J. F. (Principal Investigator (PI)), Schmidt, E. (Principal Investigator (PI)), Köhl, J. (Principal Investigator (PI)), Ehlers, M. (Principal Investigator (PI)), Hirose, M. (Principal Investigator (PI)), König, P. (Principal Investigator (PI)), Ludwig, R. (Principal Investigator (PI)), Manz, R. (Principal Investigator (PI)), Schwaninger, M. (Principal Investigator (PI)), Beek, N. (Principal Investigator (PI)), Erdmann, J. (Principal Investigator (PI)), König, I. R. (Principal Investigator (PI)), Verschoor, A. (Principal Investigator (PI)), Karsten, C. (Principal Investigator (PI)), Bieber, K. (Principal Investigator (PI)) & Busch, H. S. (Principal Investigator (PI))

    01.04.1531.12.23

    Project: DFG ProjectsDFG Joint Research: Research Units/Clinical Research Units

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