OP0128 DISTINCT FEATURES OF HLA-DR+ AND HLA-DR- PD-1HI CXCR5- T PERIPHERAL HELPER CELLS IN SEROPOSITIVE RHEUMATOID ARTHRITIS

Background: PD-1hi CXCR5- T peripheral helper (Tph) cells are newly identified pathogenic CD4+ helper T cells in rheumatoid arthritis (RA). Since Tph cells have been emerged quite recently, the characteristics of Tph cells as a biomarker of RA are not fully understood. Objectives: The aim of the study is to evaluate how useful Tph cells in peripheral bloods are when compared to other immune cell subsets, and to clarify which Tph subset most accurately reflects the disease activity of RA. Methods: The RA patients who visited our rheumatology department between January 2000 and February 2017, and met the 2010 ACR/European League Against Rheumatism (EULAR) classification criteria were included. We first assessed correlation with 40 immune cell subsets and the disease activity of RA. Next, the proportions of these immune cells were compared between RA and healthy controls (HCs). We also investigated the immune cell subsets which reflected the time course change of the disease activity after the methotrexate (MTX) treatment. The study protocol was approved by the ethics committee at Keio University School of Medicine. Results: Thirty-four seropositive RA, 12 seronegative RA and 34 HCs were included. The Immune cell subsets which showed correlation with DAS28-ESR (r> 0.2 or r> -0.2) were activated CD4 T cells (r= 0.31), HLA-DR+Th1 cells (r= 0.20), HLA-DR+Th1-17 cells (r= 0.25), Tfh1-17 cells (r= -0.25), HLA-DR+Tph cells (r= 0.22), CD3+CD8+naive T cells (r= -0.25), CD3+CD8+effector memory T cells (r= -0.26), plasma cells (r= 0.40) and CD14++CD16+intermediate monocyte (r= 0.23). The proportions of HLA-DR+Th1 cells (2.3% vs. 5.7%), HLA-DR+Th1-17 cells (0.7% vs. 2.2%), Tfh1-17 cells (1.7% vs. 2.0%), HLA-DR+Tph cells (0.02% vs. 0.1%), CD3+CD8+effector memory T cells (16.6% vs 25.7%), plasma cells (0.04% vs. 0.17%) were statistically higher in the patients with RA compared to HCs. While the proportion of Tph cells showed weak correlation with DAS28-ESR (r= 0.18), that was extremely higher in RA (0.08% vs. 0.25%). Interestingly, when assessing the correlations with the disease activity in seropositive and seronegative RA separately, the proportions of Tph cells (r= 0.52) and HLA-DR+Tph cells (r= 0.50) were highly reflected in seropositive RA, but not in seronegative RA. Regarding the disease activity after the MTX treatment, the change of proportion of Tph cells between week 0 and 52 significantly reflected the change of DAS28-ESR (r= 0.75, p= 0.025), but not HLA-DR+Tph cells because of the non-specific reduction by the MTX treatment. Rather, HLA-DR-Tph cells significantly reflected the change of DAS28-ESR while receiving the MTX treatment (r= 0.76, p= 0.021). Conclusion: Tph cells and HLA-DR+Tph cells highly reflected the disease activity of seropositive RA. However, after the treatment, the proportion of HLA-DR+Tph cells decreased independent from the disease activity, and that of HLA-DR-Tph cells more accurately reflected the change of the disease activity during the treatment. References: [1]Rao DA, et al. Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis. Nature. 2017;542:110-114. Disclosure of Interests: Hiroki Yamada: None declared, Takanori Sasaki: None declared, Katsuya Suzuki: None declared, Masaru Takeshita: None declared, Shuhei Tanemura Employee of: I am employed by Mitsubishi Tanabe Pharma Corporation, Noriyasu Seki Employee of: I am employed by Mitsubishi Tanabe Pharma Corporation, Hideto Tsujimoto Employee of: I am employed by Mitsubishi Tanabe Pharma Corporation, Tsutomu Takeuchi Grant/research support from: Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Takeda Pharmaceutical Company Ltd, UCB Pharma, Shionogi & Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co. Ltd., Consultant of: Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., Eli Lilly Japan KK, Speakers bureau: AbbVie GK, Eisai Co., Ltd, Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, AYUMI Pharmaceutical Corp., Eisai Co., Ltd, Daiichi Sankyo Co., Ltd., Gilead Sciences, Inc., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd.