Research Article
Effects of infliximab therapy on gene expression levels of tumor necrosis factor α, tristetraprolin, T cell intracellular antigen 1, and Hu antigen R in patients with rheumatoid arthritis
Makoto Sugihara, Akito Tsutsumi, Eiji Suzuki, Ei Wakamatsu, Takeshi Suzuki, Hiroshi Ogishima, Taichi Hayashi, Yusuke Chino, Wataru Ishii, Mizuko Mamura, Daisuke Goto, Isao Matsumoto, Satoshi Ito, Takayuki Sumida,
Corresponding Author
Takayuki Sumida
University of Tsukuba, Tsukuba, Japan
Division of Clinical Immunology, Major of Advanced Biomedical Applications, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, JapanSearch for more papers by this authorMakoto Sugihara, Akito Tsutsumi, Eiji Suzuki, Ei Wakamatsu, Takeshi Suzuki, Hiroshi Ogishima, Taichi Hayashi, Yusuke Chino, Wataru Ishii, Mizuko Mamura, Daisuke Goto, Isao Matsumoto, Satoshi Ito, Takayuki Sumida,
Corresponding Author
Takayuki Sumida
University of Tsukuba, Tsukuba, Japan
Division of Clinical Immunology, Major of Advanced Biomedical Applications, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, JapanSearch for more papers by this authorAbstract
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 α (TNFα) by binding to TNF messenger RNA (mRNA). TTP promotes deadenylation, TIA-1 inhibits translation, and HuR stabilizes TNFα mRNA. The aims of this study were to understand the posttranscriptional control of TNFα production in patients with rheumatoid arthritis (RA), and to identify parameters that may predict the efficacy of anti-TNFα 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. TNFα, 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:TNFα, TTP:HuR, and TIA-1:TNFα gene expression ratios were lower in patients with RA than in control subjects, while expression of TNFα, 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 TNFα and TTP, TNFα and TIA-1, TIA-1 and HuR, and TNFα 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.
Conclusion
Differences in ABP gene expression may affect TNFα gene expression. A higher TIA-1:HuR expression ratio might correlate with the response to infliximab therapy.
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