Regulation of peripheral classical and non-classical monocytes on infliximab treatment in patients with rheumatoid arthritis and ankylosing spondylitis

Aeberli, Daniel; Kamgang, Richard; Balani, Deepak H.; Hofstetter, Willy; Villiger, Peter M.; Seitz, Michael

doi:10.1136/rmdopen-2015-000079

Cited by 16 publications

(13 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These changes in frequency were accompanied by a nonsignificant decrease in CD51/CD61 ( α v β 3 integrin) and RANK surface expression in all subsets. In accordance with our results, a recent study showed a reduction in classical monocyte subpopulation and an increase in the nonclassical subpopulation following infliximab therapy [ 33 ]. Moreover, Sprangers et al observed that although nonclassical monocytes can also differentiate into OC, these cells have lower resorptive ability [ 34 ], which might explain why we did not observe bone resorption increase.…”

Section: Discussionsupporting

confidence: 93%

Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid Arthritis

Perpétuo

Caetano-Lopes

Rodrigues

et al. 2017

BioMed Research International

View full text Add to dashboard Cite

Objective. Tumor necrosis factor (TNF) increases circulating osteoclast (OC) precursors numbers by promoting their proliferation and differentiation. The aim of this study was to assess the effect of TNF inhibitors (TNFi) on the differentiation and activity of OC in rheumatoid arthritis (RA) patients. Methods. Seventeen RA patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers, in vitro OC differentiation assays, and qRT-PCR for OC specific genes was performed. Results. After TNFi therapy, patients had reduced RANKL surface expression in B-lymphocytes and the frequency of circulating classical CD14brightCD16− monocytes was decreased. Serum levels of sRANKL, sRANKL/OPG ratio, and CTX-I were reduced in RA patients after TNFi treatment. Moreover, after exposure to TNFi, osteoclast differentiation and activity were decreased, as well as the expression of TRAF6 and cathepsin K. Conclusion. We propose that TNFi arrests bone loss and erosion, through two pathways: direct reduction of osteoclast precursor numbers and inhibition of intracellular signaling pathways acting through TRAF6.

show abstract

Section: Discussionsupporting

confidence: 93%

Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid Arthritis

Perpétuo

Caetano-Lopes

Rodrigues

et al. 2017

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…This increase was associated with lower integrin expression on the surface of monocytes. A decline in the number of classical monocytes was previously reported in a small unrandomized study of 10 (5 RA, 5 AS) patients treated with infliximab, where a rapid decrease in classical monocyte subsets was reported [15]. Aeberli et al suggested that TNFi treatment might restrict monocyte recruitment into inflamed tissues and TNFi-induced apoptosis in peripheral blood monocytes, which was also reported earlier [15,16].…”

Section: Discussionsupporting

confidence: 55%

TNF-α Inhibitors Decrease Classical CD14hiCD16− Monocyte Subsets in Highly Active, Conventional Treatment Refractory Rheumatoid Arthritis and Ankylosing Spondylitis

Batko¹,

Schramm‐Luc

Skiba

et al. 2019

IJMS

View full text Add to dashboard Cite

Monocytes are pivotal cells in inflammatory joint diseases. We aimed to determine the effect of TNF-α inhibitors (TNFi) on peripheral blood monocyte subpopulations and their activation in ankylosing spondylitis (AS) and rheumatoid arthritis (RA) patients with high disease activity. To address this, we studied 50 (32 AS, 18 RA) patients with highly active disease with no prior history of TNFi use who were recruited and assigned to TNFi or placebo treatment for 12 weeks. Cytometric and clinical assessment was determined at baseline, four, and 12 weeks after initiation of TNFi treatment. We observed that treatment with TNFi led to a significant decrease in CD14hiCD16− monocytes in comparison to placebo, while circulating CD14dimCD16+ monocytes significantly increased. The TNFi-induced monocyte subset shifts were similar in RA and AS patients. While the percentage of CD14dimCD16+ monocytes increased, expression of CD11b and CD11c integrins on their surface was significantly reduced by TNFi. Additionally, CD45RA+ cells were more frequent. The shift towards nonclassical CD14dimCD16+ monocytes in peripheral blood due to TNFi treatment was seen in both AS and RA. This may reflect reduced recruitment of these cells to sites of inflammation due to lower inflammatory burden, which is associated with decreased disease activity.

show abstract

“…Studies addressing the impact of pro-inflammatory cytokine blockades on monocyte/macrophage phenotypes and functions are scarce (21, 31–33). Herein, we provide new data based on macrophages from RA patients that provide new concept of the mode of action of bDMARDs.…”

Section: Discussionmentioning

confidence: 99%

Polarization of Rheumatoid Macrophages by TNF Targeting Through an IL-10/STAT3 Mechanism

et al. 2019

View full text Add to dashboard Cite

Macrophages contribute to the pathogenesis of rheumatoid arthritis (RA). They can display different states of activation or “polarization,” notably the so-called inflammatory “M1” and the various alternative “M2” polarizations, characterized by distinct functions. Data regarding the effects of RA anti-cytokine biological disease-modifying anti-rheumatic drugs (bDMARDs) on macrophage polarization are scarce. We aimed to assess in vitro modulation of macrophage polarization by bDMARDs targeting pro-inflammatory cytokines in RA. We generated monocyte derived macrophages using blood samples from 20 RA patients with active RA and 30 healthy controls. We evaluated in vitro the impact on M1 inflammatory macrophages of: etanercept (ETA), adalimumab (ADA), certolizumab (CZP), tocilizumab (TCZ), and rituximab (RTX). We assessed the impact on macrophage polarization using flow cytometry and RTqPCR to study the expression of surface markers and perform functional studies of cytokine production, phagocytosis, and negative feedback control of inflammation. Among evaluated bDMARDs, anti-TNF agents modulated the polarization of inflammatory macrophages by decreasing inflammatory surface markers (CD40, CD80) and favoring alternative markers (CD16, CD163, MerTK). Anti-TNF agents also induced alternative functions in macrophages activated in inflammatory condition with (i) the inhibition of inflammatory cytokines (TNF, IL-6, IL-12), (ii) an increase in phagocytosis. These findings were mechanistically related to an increase in early IL-10 production, responsible for higher negative feedback control of inflammation involving SOCS3 and Gas6. This IL-10 effect was STAT3-dependent. Anti-TNF agents not only inhibit in vitro inflammatory functions of macrophages, but also favor resolution of inflammation through polarization toward alternative features specifically involving the IL-10/STAT3 axis.

show abstract

Regulation of peripheral classical and non-classical monocytes on infliximab treatment in patients with rheumatoid arthritis and ankylosing spondylitis

Cited by 16 publications

References 20 publications

Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid Arthritis

Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid Arthritis

TNF-α Inhibitors Decrease Classical CD14hiCD16− Monocyte Subsets in Highly Active, Conventional Treatment Refractory Rheumatoid Arthritis and Ankylosing Spondylitis

Polarization of Rheumatoid Macrophages by TNF Targeting Through an IL-10/STAT3 Mechanism

Contact Info

Product

Resources

About