SAT0091 INCREASED FREQUENCY AND DEFECTIVE SUPPRESIVE CAPACITY OF CD4+CD25+FOXP3+ TREG CELLS IN CHINESE PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Lan He, Bomiao Ju, Jing Zhang, Nan Hu, LI Zhu, Jian Zheng, Zijing Yin, Zhiming Hao, LV Xiaohong, Dan Pu
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Conflicting evidence exists regarding the proportion and function of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> Treg Cells in the peripheral blood (PB) of patients with rheumatoid arthritis (RA)<sup>1-6</sup>. <h3>Objectives</h3> The aim of our study was to determine whether Treg cells are defective in Chinese RA patients. <h3>Methods</h3> Levels of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> Treg cells in the peripheral blood of 224 patients with RA and 38 healthy controls were detected by flow cytometry. The expression of CTLA-4, GITR,Helios and ICOS was also evaluated in order to gain insight into the regulatory function of Treg cells. The production of IFN-γ, IL17 and IL10 cytokines by Treg cells was also evaluated. Clinical parameters, including DAS28_ESR, the levels of serum Anti-CCP, IgG and IgM were tested. Correlations with Treg cells were systematically analyzed. <h3>Results</h3> Compared to the healthy controls, active RA patients had significantly higher frequency of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> Treg cells (<i>P</i> &lt; 0.01). Furthermore, the CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> Treg cells expressed lower CTLA4 (<i>P</i> &lt; 0.01) and produced higher IL17 (<i>P</i> &lt; 0.05) and lower IL10 (<i>P</i> &lt; 0.05) in RA patients compared with healthy controls in vitro stimulation assay. We also found the proportions of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> Treg cells were significantly higher in Anti-CCP <sup>+</sup>patients compared Anti-CCP<sup>-</sup>patients (<i>P</i> &lt; 0.01). The frequency of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> Treg cells in RA patients was positively correlated with DAS28_ESR(<i>r</i> = 0.135, <i>P</i> = 0.043), the levels of serum Anti-CCP(<i>r</i> = 0.239,<i>P</i> &lt; 0.001),IgG(<i>r</i> = 0.239, <i>P</i> &lt; 0.001) and IgM(<i>r</i> = 0.168, <i>P</i> = 0.015). <h3>Conclusion</h3> We showed higher frequency of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> Treg cells in PB of RA patients, of which the suppressive capacity was defective. <h3>References</h3> [1] Vitales-Noyola M, Layseca-Espinosa E, Baranda L, et al. Analysis of Sodium Chloride Intake and Treg/Th17 Lymphocytes in Healthy Individuals and Patients with Rheumatoid Arthritis or Systemic Lupus Erythematosus. Journal of immunology research 2018; 2018: 9627806. [2] Han GM, O'Neil-Andersen NJ, Zurier RB, et al. CD4+CD25high T cell numbers are enriched in the peripheral blood of patients with rheumatoid arthritis. Cellular immunology2008; 253: 92-101. [3] van Amelsfort JM, Jacobs KM, Bijlsma JW, et al. CD4(+)CD25(+) regulatory T cells in rheumatoid arthritis: differences in the presence, phenotype, and function between peripheral blood and synovial fluid. Arthritis and rheumatism2004; 50: 2775-2785. [4] Furuzawa-Carballeda J, Lima G, Jakez-Ocampo J, et al. Indoleamine 2,3-dioxygenase-expressing peripheral cells in rheumatoid arthritis and systemic lupus erythematosus: a cross-sectional study. European journal of clinical investigation2011; 41: 1037-1046. [5] Kailashiya V, Singh U, Rana R, et al. Regulatory T Cells and Their Association with Serum Markers and Symptoms in Systemic Lupus Erythematosus and Rheumatoid Arthritis. Immunol Invest2018: 1-15. [6] Naciute M, Maciunaite G, Mieliauskaite D, et al. Increased Numbers of CD4(+)CD25(+) and CD8(+)CD25(+) T-Cells in Peripheral Blood of Patients with Rheumatoid Arthritis with Parvovirus B19 Infection. In vivo2017; 31: 181-185. <h3>Disclosure of Interests</h3> None declared