Intermediate monocytes correlate with CXCR3+ Th17 cells but not with bone characteristics in untreated early rheumatoid arthritis

PLoS One. 2021 Mar 26;16(3):e0249205. doi: 10.1371/journal.pone.0249205. eCollection 2021.


Background: Rheumatoid arthritis (RA) is associated with development of generalized osteoporosis. Bone-degrading osteoclasts are derived from circulating precursor cells of monocytic lineage, and the intermediate monocyte population is important as osteoclast precursors in inflammatory conditions. T cells of various subsets are critical in the pathogenesis of both RA and associated osteoporosis, but so far, no studies have examined associations between circulating intermediate monocytes, T cell subsets and bone characteristics in patients with RA. The aim of this study was to investigate the frequency of intermediate monocytes in patients with untreated early rheumatoid arthritis (ueRA) compared to healthy controls (HC), and to explore the correlation between intermediate monocytes and a comprehensive panel of T helper cell subsets, bone density and bone microarchitecture in ueRA patients.

Methods: 78 patients with ueRA fulfilling the ACR/EULAR 2010 criteria were included and compared to 29 age- and sex-matched HC. Peripheral blood samples were obtained before start of treatment and proportions of monocyte subsets and CD4+ helper and regulatory T cell subsets were analyzed by flow cytometry. Bone densitometry was performed on 46 of the ueRA patients at inclusion using DXA and HR-pQCT.

Results: Flow cytometric analyses showed that the majority of ueRA patients had frequencies of intermediate monocytes comparable to HC. The intermediate monocyte population correlated positively with CXCR3+ Th17 cells in ueRA patients but not in HC. However, neither the proportions of intermediate monocytes nor CXCR3+ Th17 cells were associated with bone density or bone microarchitecture measurements.

Conclusions: Our findings suggest that in early RA, the intermediate monocytes do not correlate with bone characteristics, despite positive correlation with circulating CXCR3+ Th17 cells. Future longitudinal studies in patients with longer disease duration are required to fully explore the potential of intermediate monocytes to drive bone loss in RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism
  • Humans
  • Monocytes / metabolism*
  • Receptors, CXCR3 / metabolism*
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism*


  • Receptors, CXCR3

Grants and funding

This work was supported with grants from the Swedish Research Council (2016-01192 (UI) and (HC)), the Novo Nordisk Foundation (19928 (UI)), the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-716421 (UI) and ALFGBG-857161 (HC)), the Association against Rheumatism (R-749971 (UI) and (HC)), King Gustav V’s 80 years’ foundation (FAI-2017-0358 (UI) and (HC)), the Nanna Svartz foundation (UI), the Emil and Wera Cornells foundation (UI), and the IngaBritt and Arne Lundberg Foundation (LU-2018-0008 and LU-2020-0010 (UI)). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.