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SAT0176 IL-6 Blockade with Tocilizumab Does Not Suppress CD4+T Cell Activation at 48 Weeks of The Treatment
  1. M. Murakami1,2,
  2. T. Kuritani2,
  3. N. Nishimoto1,2
  1. 1Tokyo Medical University
  2. 2Osaka Rheumatology Clinic, Osaka, Japan

Abstract

Background Rheumatoid arthritis (RA) is a common immflamatory autoimmune disease characterized by persistent synovitis and progressive destruction of cartilage and bone in multiple joints. The proportion of CD25+CD4+ T cells is increased in anti-citrullinated protein antibodies (ACPA) positive RA patients compared with ACPA negative RA patients. Abatacept (ABA), a biologic blocking T cell co-stimulation, decreased the proportion of CD25+CD4+ T cells and interleukin (IL)-6 levels in ACPA positive RA patients. It has been reported that CD25 expressions are increased by IL-6. Tocilizmab (TCZ) is a humanized anti-human IL-6 receptor antibody that has been developed to inhibit the IL-6 signal as a therapeutic agent.

Objectives We aimed to investigate whether IL-6 blockade with TCZ decreases the proportion of CD25+CD4+ T cells.

Methods Peripheral blood mononucleated cells (PBMCs) were obtained from 13 ACPA (+) RA patients at baseline, 24 and 48 weeks of TCZ treatment (male:female ratio = 0.077). Surface phenotypes and activation markers of T cells were analyzed with flow cytometory.

Results DAS28-ESR and SDAI were significantly reduced at 24 and 48 weeks compared with those at baseline (DAS28-ESR: 4.87±1.25 at baseline; 1.99±1.13 at 24 weeks, p<0.0001; 1.61±0.70 at 48 weeks p<0.0001; SDAI: 20.75±9.56 at baseline; 6.30±7.0 at 24 weeks,p=0.0008; 3.20±2.86 at 48 weeks, p<0.0001). The serum levels of matrix metalloproteinase (MMP)-3 were significantly decreased at 48 weeks (250.5±311.0 ng/mL at baseline; 85.1±81.8 ng/mL at 24 weeks, p=0.07; 54.9±27.2 ng/mL at 48 weeks, p=0.04). The proportion of CD4+ cells was significantly increased at 24 and 48 weeks compared with those at baseline (29.7±18.2% at baseline; 37.3±12.9% at 24 weeks, p=0.0094; 37.7±14.1% at 48 weeks, p=0.025). The proportions of CD25+CD4+ cells in CD4+ cells were not significantly different (5.7±4.2% at baseline; 6.1±3.4% at 24 weeks, p=0.795; 7.1±2.1% at 48 weeks, p=0.247). Also, the proportions of regulatory T (Treg) cells (FoxP3+CD25+CD4+ in CD4+ cells) were not significantly different (0.68±0.67% at baseline; 0.58±0.52% at 24 weeks p=0.752; 0.61±0.53% at 48 weeks, p=0.794).

Conclusions IL-6 blockade has therapeutic effects on RA patients. However, the blockade does not change proportions of CD4+CD25+ in CD4+ T cells as well as those of Treg cells. Some other mechanisms, besides a decrease in CD4+ activation or an increase in Treg cell proportion, contribute the therapeutic effect of IL-6 blockade.

Disclosure of Interest M. Murakami Grant/research support from: Chugai Pharmaceutical Co., Ltd., T. Kuritani: None declared, N. Nishimoto Grant/research support from: Chugai Pharmaceutical Co., Ltd., Consultant for: Chugai Pharmaceutical Co., Ltd.

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