Efficacy of Combination Treatment with Fingolimod (FTY720) Plus Pathogenic Autoantigen in a Glucose-6-phosphate Isomerase Peptide (GPI<sub>325–339</sub>)-Induced Arthritis Mouse Model

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  • Yoshida Yuya
    Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
  • Tsuji Takumi
    Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
  • Watanabe Sayaka
    Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
  • Matsushima Ayane
    Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
  • Matsushima Yuki
    Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
  • Banno Rie
    Aizenbashi Hospital
  • Fujita Tetsuro
    Research Institute for Production and Development
  • Kohno Takeyuki
    Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University Research Institute for Production and Development

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  • Efficacy of Combination Treatment with Fingolimod (FTY720) Plus Pathogenic Autoantigen in a Glucose-6-phosphate Isomerase Peptide (GPI₃₂₅₋₃₃₉)-Induced Arthritis Mouse Model

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Abstract

Fingolimod (FTY720) is known to have a significant therapeutic effect in various autoimmune disease models. Here, we examined FTY720 in a model of rheumatoid arthritis, induced by immunizing DBA/1 mice with a peptide consisting of residues 325 through 339 of glucose-6-phosphate isomerase (GPI325–339). The efficacy was evaluated in terms of macroscopic findings, inflammatory cell infiltration and autoantibody level. Prophylactic administration of FTY720 from the day of immunization significantly suppressed the development of paw swelling, but therapeutic administration of FTY720 from onset of symptoms on day 8–9 was less effective. Interestingly, however, combination treatment with FTY720 plus GPI325–339 for 5 d after onset of symptoms significantly reduced the severity of symptoms in all mice, and no relapse occurred after booster immunization. Taking into account the reported mechanism of action of FTY720, these results indicate that combination treatment with FTY720 plus pathogenic autoantigen might efficiently induce immune tolerance by sequestering circulating autoantigen-specific lymphocytes from blood and peripheral tissues to the secondary lymphoid tissues. Combination treatment with FTY720 plus pathogenic autoantigen may become a breakthrough treatment for remission-induction in patients with autoimmune diseases including rheumatoid arthritis.

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