Transcriptomic profile comparison of monocytes from rheumatoid arthritis patients in treatment with methotrexate, anti-TNFa, abatacept or tocilizumab

PLoS One. 2023 Mar 6;18(3):e0282564. doi: 10.1371/journal.pone.0282564. eCollection 2023.

Abstract

It is well documented that patients affected by rheumatoid arthritis (RA) have distinct susceptibility to the different biologic DMARDs available on the market, probably because of the many facets of the disease. Monocytes are deeply involved in the pathogenesis of RA and we therefore evaluated and compared the transcriptomic profile of monocytes isolated from patients on treatment with methotrexate alone or in combination with tocilizumab, anti-TNFα or abatacept and from healthy donors. Whole-genome transcriptomics yielded a list of regulated genes by Rank Product statistics and DAVID was then used for functional annotation enrichment analysis. Last, data were validated by qRT-PCR. Abatacept, tocilizumab and anti-TNFa cohorts were separately compared with methotrexate, leading to the identification of 78, 6, and 436 differentially expressed genes, respectively. The upper-most ranked genes were related to inflammatory processes and immune responses. Such an approach draws the genomic profile of monocytes in treated RA patients and lays the basis for finding gene signature for tailored therapeutic choices.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept* / pharmacology
  • Abatacept* / therapeutic use
  • Arthritis, Rheumatoid* / drug therapy
  • Arthritis, Rheumatoid* / genetics
  • Humans
  • Methotrexate* / pharmacology
  • Methotrexate* / therapeutic use
  • Monocytes
  • Transcriptome*
  • Tumor Necrosis Factor Inhibitors* / pharmacology
  • Tumor Necrosis Factor Inhibitors* / therapeutic use

Substances

  • Abatacept
  • Methotrexate
  • tocilizumab
  • Tumor Necrosis Factor Inhibitors

Grants and funding

LGF CREARE2016, RF09 2.0 Pfizer The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.