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01.08.2011 | Research article | Ausgabe 4/2011 Open Access

Arthritis Research & Therapy 4/2011

Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-α therapy

Zeitschrift:
Arthritis Research & Therapy > Ausgabe 4/2011
Autoren:
Der-Yuan Chen, Yi-Ming Chen, Hsin-Hua Chen, Chia-Wei Hsieh, Chi-Chen Lin, Joung-Liang Lan
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​ar3431) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

DYC and JLL participated in the study design, acquisition of data, interpretation of results, and manuscript preparation. YMC participated in the study design, acquisition of data, interpretation of results, and assisted in drafting the manuscript. HHC, CWH and CCL contributed to analysis and interpretation of data, and assisted in drafting the manuscript. All authors approved the final manuscript.

Abstract

Introduction

The objective of this study was to investigate the effects of tumor necrosis factor (TNF)-α inhibitors on circulating T helper-type 17 (Th17) cells and Th17-related cytokines in patients with rheumatoid arthritis (RA).

Methods

The frequencies of circulating Th17 cells and serum levels of Th17-related cytokines were determined using flow cytometry analysis and ELISA, respectively, in 48 RA patients both before (baseline) and six months after anti-TNF-α therapy. Therapeutic response was evaluated using European League Against Rheumatism (EULAR) response criteria.

Results

Significantly higher baseline frequencies of circulating Th17 cells and serum levels of interleukin (IL)-6, IL-17, IL-21, IL-23 and TNF-α were observed in active RA patients than in 12 healthy controls (all P < 0.001). After anti-TNF-α therapy, 36 patients (75%) were EULAR responders (20 good responders and 16 moderate responders) and 12 (25.0%) were non-responders. The mean levels of circulating Th17 cells and IL-17 significantly decreased (1.13% vs. 0.79%; 43.1 pg/ml vs. 27.8 pg/ml; respectively, both P < 0.001) in parallel with clinical remission in responders. Levels of IL-6, IL-21, IL-23 and TNF-α were significantly decreased after anti-TNF-α therapy in responders. In contrast, the mean levels of circulating Th17 cells and IL-17 significantly increased after anti-TNF-α therapy (2.94% vs. 4.23%; 92.1 pg/ml vs. 148.6 pg/ml; respectively, both P < 0.05) in non-responders. Logistic regression analysis identified a high baseline level of IL-17 as a significant predictor of poor therapeutic response.

Conclusions

The beneficial effect of anti-TNF-α therapy might involve a decrease in Th17-related cytokines in responders, whereas rising levels of circulating Th17-cells and IL-17 were observed in patients with an inadequate response to anti-TNF-α therapy.
Zusatzmaterial
Authors’ original file for figure 1
13075_2011_3191_MOESM1_ESM.pdf
Authors’ original file for figure 2
13075_2011_3191_MOESM2_ESM.pdf
Literatur
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