TY - JOUR
T1 - Multi-omics monitoring of drug response in rheumatoid arthritis in pursuit of molecular remission
AU - Tasaki, Shinya
AU - Suzuki, Katsuya
AU - Kassai, Yoshiaki
AU - Takeshita, Masaru
AU - Murota, Atsuko
AU - Kondo, Yasushi
AU - Ando, Tatsuya
AU - Nakayama, Yusuke
AU - Okuzono, Yuumi
AU - Takiguchi, Maiko
AU - Kurisu, Rina
AU - Miyazaki, Takahiro
AU - Yoshimoto, Keiko
AU - Yasuoka, Hidekata
AU - Yamaoka, Kunihiro
AU - Morita, Rimpei
AU - Yoshimura, Akihiko
AU - Toyoshiba, Hiroyoshi
AU - Takeuchi, Tsutomu
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-018-05044-4
DO - 10.1038/s41467-018-05044-4
M3 - Article
C2 - 30013029
AN - SCOPUS:85050404860
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2755
ER -