Anti-tumour necrosis factor treatment increases circulating T helper type 17 cells similarly in different types of inflammatory arthritis

Abstract

We investigated changes in circulating T helper type 17 (Th17) cells following anti-tumour necrosis factor (TNF) in rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients. Peripheral blood mononuclear cells (PBMC) were isolated from 25 RA, 15 AS and eight PsA patients at baseline 4 and 12 weeks after treatment, and Th17 cell frequencies were analysed using interleukin (IL)-17 enzyme-linked immunospot (ELISPOT) and flow cytometry. A significant increase in IL-17-producing cells was observed by ELISPOT in RA and AS patients at 12 weeks. Flow cytometry confirmed significant increases in CD4(+) IL-17(+) cells at 12 weeks in RA and AS and 4 weeks in PsA patients. Anti-TNF treatment increases circulating Th17 cells in three different diseases.

Trial registration: ClinicalTrials.gov NCT01060098.

Keywords: T cells; ankylosing spondylitis; anti-TNF; psoriatic arthritis; rheumatoid arthritis.

© 2015 British Society for Immunology.

Figures

Fig. 1

Changes in frequency of T helper type 17 (Th17) cells in peripheral blood during 12 weeks of anti-tumour necrosis factor (TNF) treatment. Changes in numbers of interleukin (IL)-17-producing peripheral blood mononuclear cells (PMBC) during anti-TNF treatment as determined by IL-17 enzyme-linked immunospot (ELISPOT) assay are shown for rheumatoid arthritis (RA) patients (n = 25) (a), ankylosing spondylitis (AS) patients (n = 15) (b), psoriatic arthritis (PsA) patients (n = 8) (c) and the whole study cohort (n = 48 patients); (d) 200 000 PBMC were seeded in triplicate in each experiment and stimulated with 1 μg/ml anti-CD3 antibody for 20 h and the numbers of cytokine-producing cells were enumerated. Changes in the percentages of circulating CD4+IL-17+ cells in the peripheral blood of RA patients (n = 25) (d), AS patients (n = 15) (e), PsA patients (n = 8) (f) and the whole study cohort (n = 48 patients) (g) as determined by flow cytometry. Bars represent mean ± standard error of the mean (s.e.m.). *P < 0·05, **P < 0·01 versus baseline visit by Wilcoxon's matched-pairs test. spSFC/106 = specific spot-forming cells per million PBMC.

Fig. 2

Anti-tumour necrosis factor (TNF) treatment with adalimumab and etanercept leads to an increase in frequency of circulating T helper type 17 (Th17) cells in peripheral blood. The kinetics of change of circulating interleukin (IL)-17-producing cells during anti-TNF treatment were the same in rheumatoid arthritis (RA) patients treated with etanercept (n = 18) (a) and with adalimumab (n = 7) (b), as determined by IL-17 enzyme-linked immunospot (ELISPOT) assay; 200 000 PBMC were seeded in triplicate in each experiment and stimulated with 1 μg/ml anti-CD3 antibody for 20 h and the numbers of cytokine-producing cells were enumerated. The percentages of circulating CD4+IL-17+ cells in the peripheral blood of RA patients increased similarly in patients treated with etanercept (n = 18) (c) and adalimumab (n = 7) (d). Bars represent mean ± standard error of the mean (s.e.m.). *P < 0·05, **P < 0·01 versus baseline visit by Wilcoxon's matched-pairs test. spSFC/106 = specific spot-forming cells per million PBMC.