title: The balance between Foxp3 and Ror-γt expression in peripheral blood is altered by tocilizumab and abatacept in patients with rheumatoid arthritis.
abstract: The balance between Th17 cells and regulatory T (Treg) cells has been shown to play an important role in the development of rheumatoid arthritis (RA). Recent studies have shown that treatment with abatacept (ABT) or tocilizumab (TCZ) affects Th17 and Treg cell populations. Although not unanimously accepted, several reports have shown that Treg cells are decreased by ABT and increased by TCZ, and that Th17 cells are decreased by TCZ. To further investigate the effects of ABT and TCZ on the skewing of T cell populations, we analyzed the expression of master regulators genes of helper T cell lineages following ABT/TCZ treatment of RA patients.
  
  
  
  Ten patients treated with ABT and 10 patients treated with TCZ were enrolled. Total RNA was extracted from peripheral blood cells at baseline, and after 12 and 24 weeks of therapy. The expression levels of T-bet, GATA3, Foxp3 and Ror-γt were semi-quantified using real-time PCR. The relative expression levels were expressed as the ratios of two genes (T-bet/GATA3, Foxp3/GATA3, Foxp3/T-bet, Foxp3/Ror-γt, Ror-γt/T-bet, Ror-γt/GATA3), and the changes in these ratios with treatment were determined.
  
  
  
  The Foxp3/Ror-γt ratio was decreased after ABT therapy (0.67 ± 0.16 at 24 weeks, P = 0.0034) but was increased after TCZ therapy (2.00 ± 1.03 at 24 weeks, P = 0.0013). In addition, the Ror-γt/GATA3 ratio was decreased after TCZ therapy (0.78 ± 0.37 at 24 weeks, P = 0.0008). Except for these ratios, no significant skewing in the expression of these factors was detected. No significant relationship between clinical response to the treatment and change in the ratios of these factors was determined.
  
  
  
  Treatment with TCZ or ABT differently affected the balance between Foxp3 and Ror-γt expression in the peripheral blood of patients with RA.
authors.affiliation: Department of Rheumatology, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan. taday@cc.saga-u.ac.jp.
authors.forename: Yoshifumi
authors.identifier: 0000-0003-0742-831X
authors.initials: Y
authors.lastname: Tada
authors.affiliation: Department of Rheumatology, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ono
authors.affiliation: Department of Rheumatology, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Suematsu
authors.affiliation: Department of Rheumatology, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Tashiro
authors.affiliation: Department of Rheumatology, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Sadanaga
authors.affiliation: Department of Rheumatology, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Tokuda
authors.affiliation: Department of Rheumatology, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Ono
authors.affiliation: Department of Rheumatology, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Nakao
authors.affiliation: Department of Rheumatology, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Maruyama
authors.affiliation: Department of Nursing, Faculty of Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Ohta
authors.affiliation: Department of Rheumatology, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
authors.forename: Syuichi
authors.initials: S
authors.lastname: Koarada
mesh_terms: D000069594:Abatacept / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects* / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D000069594:Abatacept; C502936:tocilizumab
keywords: Abatacept; Foxp3; Ror-γt; Tocilizumab