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Targeting antibody-mediated complement-independent mechanism in bullous pemphigoid with diacerein.
- Source :
-
Journal of dermatological science [J Dermatol Sci] 2024 Apr; Vol. 114 (1), pp. 44-51. Date of Electronic Publication: 2024 Mar 06. - Publication Year :
- 2024
-
Abstract
- Background: Bullous pemphigoid (BP) is an antibody-mediated blistering disease predominantly affecting the elderly. The pathogenesis involves both complement-dependent and complement-independent mechanisms. The therapeutic potential of targeting complement-independent mechanism has not yet been determined. The mainstay of treatment, corticosteroid, has many side effects, indicating the needs of better treatments.<br />Objective: We tempted to establish an in vitro model of BP which resembles complement-independent mechanism and to examine the therapeutic potential of a novel anti-inflammatory agent, diacerein.<br />Methods: Cultured HaCaT cells were treated with purified antibodies from BP patients, with or without diacerein to measure the cell interface presence of BP180, protein kinase C, and the production of proinflammatory cytokines. An open-label, randomized, phase 2 trial was conducted to compare topical diacerein and clobetasol ointments in patients with mild-to-moderate BP (NCT03286582).<br />Results: The reduced presentation of BP180 at cell interface after treating with BP autoantibodies was noticed in immunofluorescence and western blotting studies. The phenomenon was restored by diacerein. Diacerein also reduced the autoantibody-induced increase of pro-inflammatory cytokines. Reciprocal changes of BP180 and protein kinase C at the cell interface were found after treating with BP autoantibodies. This phenomenon was also reversed by diacerein in a dose-dependent manner. The phase 2 trial showed that topical diacerein reduced the clinical symptoms which were comparable to those of topical clobetasol.<br />Conclusion: Diacerein inhibited BP autoantibody-induced reduction of BP180 and production of proinflammatory cytokines in vitro and showed therapeutic potential in patients with BP. It is a novel drug worthy of further investigations.<br />Competing Interests: Declaration of Competing Interest Ms. Lee JY was an employee of Twi Biotechnology.<br /> (Copyright © 2024 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Aged
Female
Humans
Male
Anti-Inflammatory Agents therapeutic use
Anti-Inflammatory Agents pharmacology
Autoantigens immunology
Cell Line
Clobetasol therapeutic use
Clobetasol pharmacology
Collagen Type XVII
Complement System Proteins immunology
HaCaT Cells
Keratinocytes immunology
Keratinocytes drug effects
Protein Kinase C antagonists & inhibitors
Protein Kinase C metabolism
Protein Kinase C immunology
Treatment Outcome
Anthraquinones pharmacology
Anthraquinones therapeutic use
Autoantibodies immunology
Autoantibodies blood
Cytokines metabolism
Cytokines immunology
Non-Fibrillar Collagens immunology
Pemphigoid, Bullous immunology
Pemphigoid, Bullous drug therapy
Pemphigoid, Bullous pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-569X
- Volume :
- 114
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of dermatological science
- Publication Type :
- Academic Journal
- Accession number :
- 38508975
- Full Text :
- https://doi.org/10.1016/j.jdermsci.2024.03.001