title: Efficacy of combination treatment with fingolimod (FTY720) plus pathogenic autoantigen in a glucose-6-phosphate isomerase peptide (GPI325-339)-induced arthritis mouse model.
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.
authors.affiliation: Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Takumi
authors.initials: T
authors.lastname: Tsuji
authors.forename: Sayaka
authors.initials: S
authors.lastname: Watanabe
authors.forename: Ayane
authors.initials: A
authors.lastname: Matsushima
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsushima
authors.forename: Rie
authors.initials: R
authors.lastname: Banno
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Fujita
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Kohno
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D000068876:Fingolimod Hydrochloride; D005956:Glucose-6-Phosphate Isomerase / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010455:Peptides; D011409:Propylene Glycols / Q000008:administration & dosage*; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D010455:Peptides; D011409:Propylene Glycols; D005956:Glucose-6-Phosphate Isomerase; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine