Article Text

PDF
AB0163 Factors associated with the expansion of TH17 cells in peripheral blood of ra patients: Possible different effect between anti-IL-6 and anti-TNF therapies
  1. J. Kikuchi1,
  2. M. Shiina2,
  3. M. Hashizume2,
  4. M. Mihara2,
  5. K. Yoshimoto1,
  6. H. Kameda1,
  7. T. Takeuchi1
  1. 1Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo
  2. 2Product Research Department, Chugai Pharmaceutical Co., Ltd., Gotenba, Japan

Abstract

Background Th17 cells play an important role in many animal models of autoimmune arthritis. However, pathophysiological roles of Th17 cells in patients with rheumatoid arthritis (RA), as well as the impact of RA treatment on Th17 population in those patients have not been elucidated. Recently, CD161, a C-type lectin-like receptor, has been described as a cell surface marker of human Th17 cells.

Objectives To examine whether Th17 population is altered by the presence of RA and the treatment for it, we investigated the percentage of CD4+CD161+CD45RO+CCR6+ cells (defined as human Th17) in total CD4+ T cells in peripheral blood from healthy adults (HA) and patients with RA stratified by treatments.

Methods Peripheral blood was collected from 81 RA patients and 17 HA. The mean (±SD) age of RA patients was 55.6±14.4 years, with the mean disease duration of 6.2±7.0 years. Among a total of 81 RA patients, 7 patients have not been treated with any DMARDs or biologics until the blood isolation, while 19 patients were receiving DMARDs alone, 29 receiving TNF inhibitors, and 26 receiving tocilizumab (TCZ). Four-color flow cytometry was used to analyze the surface phenotype of freshly isolated peripheral blood.

Results The mean (±SD) values of DAS28-ESR in untreated RA patients, those with DMARDs, TNF inhibiters and TCZ were 4.68±0.89, 4.98±1.01, 2.72±0.94, 2.16±0.94, respectively. The mean percentages of Th17 in CD4+ T cells were not significantly different between RA patients (5.8%) and HA (4.8%). However, the percentage of patients with high Th17 rate (defined as above the mean+2SD value in HA) was 0% in HA and 23% in RA patients, respectively. Among RA patients, the mean percentage of Th17 in CD4+ T cells in untreated patients was 8.3% (range: 6.0-12.6%), which was significantly higher than that in any treatment groups (DMARDs alone, TNF inhibitors or TCZ; p<0.01). Similarly, the highest rate of Th17-high patients was observed in untreated RA patients (71.4%). Interestingly, the rate of Th17-high patients was 37.9% in those receiving TNF inhibitors, which was greater than those receiving DMARDs alone (10.5%) or TCZ (3.8%). Furthermore, among patients receiving TNF inhibitors, the percentage of Th17-high patients was 66.7% in those with the high titer of anti-CCP antibody (>100 U/ml), which was significantly greater than that in the remaining patients (16.7%; p<0.05). Finally, a multivariable analysis including clinical parameters identified the undergoing treatment and the high titer of anti-CCP antibody as independent factors associated with the high percentage of Th17 in RA patients.

Conclusions Th17 ratio in peripheral blood CD4+ T cells may be determined by autoantibody profiles and the undergoing treatment status in patients with RA. Although clinical efficacy of anti-IL-6 and anti-TNF therapies seemed to be comparable in this study, these treatments showed different effects on Th17 cells in peripheral blood of RA patients.

Disclosure of Interest None Declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.