title: Effects of infliximab therapy on gene expression levels of tumor necrosis factor alpha, tristetraprolin, T cell intracellular antigen 1, and Hu antigen R in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Tristetraprolin (TTP), T cell intracellular antigen 1 (TIA-1), and Hu antigen R (HuR) are adenine/uridine-rich element binding proteins (ABPs) that affect the production of tumor necrosis factor alpha (TNFalpha) by binding to TNF messenger RNA (mRNA). TTP promotes deadenylation, TIA-1 inhibits translation, and HuR stabilizes TNFalpha mRNA. The aims of this study were to understand the posttranscriptional control of TNFalpha production in patients with rheumatoid arthritis (RA), and to identify parameters that may predict the efficacy of anti-TNFalpha therapy.
  
  
  METHODS
  Peripheral blood mononuclear cells from 38 patients with RA were obtained before therapy and 2 weeks and 54 weeks after administration of the first dose of infliximab, and from 20 healthy control subjects. TNFalpha, TTP, TIA-1, and HuR gene expression levels were analyzed by real-time polymerase chain reaction.
  
  
  RESULTS
  At baseline, TTP and HuR gene expression levels, as well as the TTP:TNFalpha, TTP:HuR, and TIA-1:TNFalpha gene expression ratios were lower in patients with RA than in control subjects, while expression of TNFalpha, TIA-1, and TIA-1:HuR was higher in patients with RA. The TTP:HuR expression ratio decreased significantly after administration of infliximab. Positive correlations were observed between TNFalpha and TTP, TNFalpha and TIA-1, TIA-1 and HuR, and TNFalpha and HuR gene expression in both healthy control subjects and patients with RA. At baseline, the TIA-1:HuR ratio tended to be higher in patients who achieved 50% improvement according to the American College of Rheumatology criteria (ACR50) at week 54 than in those who did not achieve at least an ACR20 response.
  
  
  CONCLUSIONS
  Differences in ABP gene expression may affect TNFalpha gene expression. A higher TIA-1:HuR expression ratio might correlate with the response to infliximab therapy.
authors.affiliation: University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sugihara
authors.forename: Akito
authors.initials: A
authors.lastname: Tsutsumi
authors.forename: Eiji
authors.initials: E
authors.lastname: Suzuki
authors.forename: Ei
authors.initials: E
authors.lastname: Wakamatsu
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ogishima
authors.forename: Taichi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Chino
authors.forename: Wataru
authors.initials: W
authors.lastname: Ishii
authors.forename: Mizuko
authors.initials: M
authors.lastname: Mamura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Goto
authors.forename: Isao
authors.initials: I
authors.lastname: Matsumoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ito
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sumida
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000954:Antigens, Surface / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D000069285:Infliximab; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D039102:Poly(A)-Binding Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D012016:Reference Values; D000074019:T-Cell Intracellular Antigen-1; D051816:Tristetraprolin / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D039102:Poly(A)-Binding Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D051816:Tristetraprolin; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab