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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