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

Nature Communications
Shinya TasakiTsutomu Takeuchi

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.

References

Nov 30, 2000·The New England Journal of Medicine·P E LipskyUNKNOWN Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group
Apr 25, 2006·Biostatistics·W Evan JohnsonAriel Rabinovic
May 16, 2006·European Journal of Haematology·Yair HerishanuRafael Marilus
Oct 3, 2007·PLoS Genetics·Jeffrey T Leek, John D Storey
Aug 1, 1996·Journal of Clinical Rheumatology : Practical Reports on Rheumatic & Musculoskeletal Diseases·K M Syed, R S Pinals
Dec 8, 2009·Rheumatic Diseases Clinics of North America·Jaap Fransen, Piet L C M van Riel
Oct 12, 2010·PloS One·Ilya KupershmidtMostafa Ronaghi
Apr 7, 2011·Nature Reviews. Rheumatology·Benjamin RhodesTimothy J Vyse
Dec 14, 2011·The New England Journal of Medicine·Iain B McInnes, Georg Schett
Feb 22, 2012·Nature Reviews. Immunology·Holden T MaeckerRobert Nussenblatt
Jan 18, 2013·BMC Bioinformatics·Sonja HänzelmannJustin Guinney
Jan 23, 2014·Arthritis & Rheumatology·Julie DucreuxBernard R Lauwerys
Jul 25, 2014·Annals of the Rheumatic Diseases·Bing LuElizabeth W Karlson
Jan 22, 2015·Nucleic Acids Research·Matthew E RitchieGordon K Smyth
Jan 27, 2015·Joint, Bone, Spine : Revue Du Rhumatisme·Florenzo IannoneGiovanni Lapadula
Jul 2, 2015·Expert Review of Clinical Pharmacology·Hanna L GulPaul Emery
Aug 4, 2015·Arthritis Research & Therapy·György Nagy, Ronald F van Vollenhoven
Jan 16, 2016·Cell Systems·Arthur LiberzonPablo Tamayo
May 18, 2016·Arthritis Research & Therapy·Ayumi NishikawaTsutomu Takeuchi
Dec 3, 2016·Nature Reviews. Gastroenterology & Hepatology·Siddharth SinghWilliam J Sandborn
Mar 7, 2017·Nature Immunology·Jan C RieckmannFelix Meissner
May 20, 2017·Annals of the Rheumatic Diseases·Shinya TasakiTsutomu Takeuchi
Aug 11, 2017·Nature Reviews. Rheumatology·Leendert A TrouwAnna M Blom

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Citations

Oct 5, 2018·European Journal of Immunology·Timothy R D J RadstakeJohannes W J Bijlsma
Dec 19, 2019·Pharmacogenomics·Stephanie F Ling, James Bluett
Feb 29, 2020·Nature Reviews. Rheumatology·Sinisa SavicMichael F McDermott
May 28, 2020·Expert Review of Clinical Immunology·Jessica R TarnJohn D Isaacs
Aug 15, 2020·Journal of Leukocyte Biology·Cesar Augusto Prada-MedinaHelder I Nakaya
Aug 31, 2020·Rheumatology·Bako NouriAnne Barton
Apr 13, 2019·Nature Reviews. Drug Discovery·Jessica VamathevanShanrong Zhao
Feb 19, 2020·Nature Reviews. Rheumatology·S A Kerrigan, I B McInnes
Jul 23, 2019·Rheumatology·Darren Plant, Anne Barton
Dec 4, 2019·Nature Medicine·Stephen A WilliamsNicholas J Wareham
Aug 31, 2019·Nature Communications·Cristina M LanataLindsey A Criswell
Jan 27, 2019·International Journal of Rheumatic Diseases·Jinxia Zhao, Zhan-Guo Li
Oct 8, 2020·Nature Reviews. Rheumatology·Deepak R JadonOliver FitzGerald
Dec 3, 2020·International Journal of Molecular Sciences·Chary Lopez-PedreraCarlos Pérez-Sánchez
Nov 13, 2020·ImmunoTargets and Therapy·Yoshiya TanakaToshio Imai
Feb 25, 2021·Expert Review of Clinical Immunology·Ikram MezghicheElisabetta Bianchi
Mar 4, 2021·Nutrients·Manuela CassottaMaurizio Battino
Nov 14, 2020·Nature Reviews. Rheumatology·Darren Plant, Anne Barton
Apr 25, 2019·The American Journal of Pathology·Laurel Yong-Hwa Lee, Joseph Loscalzo
May 1, 2021·Life·Raul Lopez-DominguezPedro Carmona-Saez
May 21, 2021·Frontiers in Immunology·Siting LiChaojun Hu
Aug 19, 2021·Scientific Reports·Jun InamoTsutomu Takeuchi
Aug 17, 2021·Artificial Intelligence Review·Suresh DaraMohamed Jawed Ahsan
Sep 8, 2021·Nature Reviews. Cancer·Gabriel A KwongSangeeta N Bhatia
Nov 4, 2021·Journal of Leukocyte Biology·Zhijie WuNeal S Young

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Datasets Mentioned

BETA
syn8483403
GSE93777

Methods Mentioned

BETA
ESR
FACS
genetic modifications

Software Mentioned

limma R
R GSVA package
Synapse
PLSR
ssGSEA
GSEA
R package
Enrichment Map 45
limma

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