Pemphigus mouse model as a tool to evaluate various immunosuppressive therapies

Yujiro Takae, Takeji Nishikawa, Masayuki Amagai

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Pemphigus vulgaris (PV) is an autoimmune bullous disease caused by immunoglobulin G (IgG) autoantibodies against desmoglein 3 (Dsg3). We have generated an active disease mouse model for PV by adoptive transfer of Dsg3-/- lymphocytes. In this study, we investigated the benefits and limitations of this model as a tool to evaluate various immunosuppressive therapeutic strategies. We used the following three measurements to evaluate the effects of the drugs during the time course: Dsg3 enzymelinked immunosorbent assay scores that represent the level of production of anti-Dsg3 IgG, body weight loss that reflects the severity of oral erosions and PV score that reflects the extent of skin lesions. We examined various immunosuppressive agents currently used to treat patients with PV model mice in preventive protocol. Cyclophosphamide almost completely suppressed the production of anti-Dsg3 IgG, development of body weight loss and the appearance of the PV phenotype in contrast with the control group without the drug. Azathioprine, cyclosporin A and tacrolimus hydrate also showed suppressive effects to various degrees. However, methylprednisolone and dexamethasone failed to show significant effects in contrast to the findings reported in humans. Knowing the advantages and limitations of this model will provide an important foundation for the future evaluation and development of novel therapeutic strategies.

Original languageEnglish
Pages (from-to)252-260
Number of pages9
JournalExperimental Dermatology
Volume18
Issue number3
DOIs
Publication statusPublished - 2009 Apr 20

Keywords

  • Autoantibody
  • Evaluation
  • Immunosuppressive therapy
  • Mouse model
  • Pemphigus vulgaris

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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