Effects of interleukin-6 signal inhibition on Treg subpopulations and association of Tregs with clinical outcomes in rheumatoid arthritis
© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology..
OBJECTIVES: Anti-IL-6 receptor antibodies are clinically efficacious in the management of rheumatoid arthritis (RA) with an associated increase in regulatory T cells (Tregs); however, the role of functional Treg subsets has yet to be clarified. This study aimed to evaluate how functional Treg subsets are altered by IL-6 receptor blockade and to analyze the relationship between these Treg subsets and the clinical outcome of RA.
METHODS: We collected frozen peripheral blood mononuclear cells (PBMCs) from 40 patients with RA who started tocilizumab (TCZ) with or without MTX and 11 healthy controls (HCs). We fractionated Tregs with flow cytometry based on markers of phenotype and function and measured the proportions of detailed Treg subsets sequentially from baseline to week 52.
RESULTS: The proportions of resting Tregs (rTregs) and rTregs+activated Tregs (aTregs) were significantly lower in RA patients at baseline than in HCs. The proportions of all those CD127low Tregs, rTregs, aTregs, and rTregs+aTregs were significantly increased with TCZ treatment. In patients treated with TCZ without MTX, rTreg were increased. Patients with an increase in the proportion of rTregs at week 12 had significantly less arthritis flares during the observation period.
CONCLUSIONS: Blocking IL-6 receptor with TCZ increased the proportion of rTregs, a functional Treg subpopulation. Patients with an early increase in rTregs showed a favorable treatment course, and this increase in rTregs may reflect molecular remission induced by IL-6 signal inhibition.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Rheumatology (Oxford, England) - (2024) vom: 26. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yoshida, Hiroto [VerfasserIn] |
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| Links: |
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| Themen: |
Interleukin-6 |
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| Anmerkungen: |
Date Revised 26.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1093/rheumatology/keae196 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM37020333X |
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| 100 | 1 | |a Yoshida, Hiroto |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effects of interleukin-6 signal inhibition on Treg subpopulations and association of Tregs with clinical outcomes in rheumatoid arthritis |
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| 500 | |a Date Revised 26.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. | ||
| 520 | |a OBJECTIVES: Anti-IL-6 receptor antibodies are clinically efficacious in the management of rheumatoid arthritis (RA) with an associated increase in regulatory T cells (Tregs); however, the role of functional Treg subsets has yet to be clarified. This study aimed to evaluate how functional Treg subsets are altered by IL-6 receptor blockade and to analyze the relationship between these Treg subsets and the clinical outcome of RA | ||
| 520 | |a METHODS: We collected frozen peripheral blood mononuclear cells (PBMCs) from 40 patients with RA who started tocilizumab (TCZ) with or without MTX and 11 healthy controls (HCs). We fractionated Tregs with flow cytometry based on markers of phenotype and function and measured the proportions of detailed Treg subsets sequentially from baseline to week 52 | ||
| 520 | |a RESULTS: The proportions of resting Tregs (rTregs) and rTregs+activated Tregs (aTregs) were significantly lower in RA patients at baseline than in HCs. The proportions of all those CD127low Tregs, rTregs, aTregs, and rTregs+aTregs were significantly increased with TCZ treatment. In patients treated with TCZ without MTX, rTreg were increased. Patients with an increase in the proportion of rTregs at week 12 had significantly less arthritis flares during the observation period | ||
| 520 | |a CONCLUSIONS: Blocking IL-6 receptor with TCZ increased the proportion of rTregs, a functional Treg subpopulation. Patients with an early increase in rTregs showed a favorable treatment course, and this increase in rTregs may reflect molecular remission induced by IL-6 signal inhibition | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Interleukin-6 | |
| 650 | 4 | |a Regulatory T cell | |
| 650 | 4 | |a Rheumatoid arthritis | |
| 650 | 4 | |a Tocilizumab | |
| 700 | 1 | |a Magi, Mayu |e verfasserin |4 aut | |
| 700 | 1 | |a Tamai, Hiroya |e verfasserin |4 aut | |
| 700 | 1 | |a Kikuchi, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Yoshimoto, Keiko |e verfasserin |4 aut | |
| 700 | 1 | |a Otomo, Kotaro |e verfasserin |4 aut | |
| 700 | 1 | |a Matsumoto, Yoshihiro |e verfasserin |4 aut | |
| 700 | 1 | |a Noguchi-Sasaki, Mariko |e verfasserin |4 aut | |
| 700 | 1 | |a Takeuchi, Tsutomu |e verfasserin |4 aut | |
| 700 | 1 | |a Kaneko, Yuko |e verfasserin |4 aut | |
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