Multi-omics monitoring of drug response in rheumatoid arthritis in pursuit of molecular remission

Shinya Tasaki, Katsuya Suzuki, Yoshiaki Kassai, Masaru Takeshita, Atsuko Murota, Yasushi Kondo, Tatsuya Ando, Yusuke Nakayama, Yuumi Okuzono, Maiko Takiguchi, Rina Kurisu, Takahiro Miyazaki, Keiko Yoshimoto, Hidekata Yasuoka, Kunihiro Yamaoka, Rimpei Morita, Akihiko Yoshimura, Hiroyoshi Toyoshiba, Tsutomu Takeuchi

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22 Citations (Scopus)

Abstract

Sustained clinical remission (CR) without drug treatment has not been achieved in patients with rheumatoid arthritis (RA). This implies a substantial difference between CR and the healthy state, but it has yet to be quantified. We report a longitudinal monitoring of the drug response at multi-omics levels in the peripheral blood of patients with RA. Our data reveal that drug treatments alter the molecular profile closer to that of HCs at the transcriptome, serum proteome, and immunophenotype level. Patient follow-up suggests that the molecular profile after drug treatments is associated with long-term stable CR. In addition, we identify molecular signatures that are resistant to drug treatments. These signatures are associated with RA independently of known disease severity indexes and are largely explained by the imbalance of neutrophils, monocytes, and lymphocytes. This high-dimensional phenotyping provides a quantitative measure of molecular remission and illustrates a multi-omics approach to understanding drug response.

Original languageEnglish
Article number2755
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Tasaki, S., Suzuki, K., Kassai, Y., Takeshita, M., Murota, A., Kondo, Y., Ando, T., Nakayama, Y., Okuzono, Y., Takiguchi, M., Kurisu, R., Miyazaki, T., Yoshimoto, K., Yasuoka, H., Yamaoka, K., Morita, R., Yoshimura, A., Toyoshiba, H., & Takeuchi, T. (2018). Multi-omics monitoring of drug response in rheumatoid arthritis in pursuit of molecular remission. Nature Communications, 9(1), [2755]. https://doi.org/10.1038/s41467-018-05044-4