AB0036 THE IMPACT OF ANTI-TNF THERAPY ON CD4+T CELL SUBSETS IN DIFFERENT DIFFERENTIATION STAGES AND TREG CELLS IN ACTIVE ANKYLOSING SPONDYLITIS
Authors: Mingcan Yang, Zetao Liao, Yutong Jiang, Jieruo Gu
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Ankylosing Spondyloarthritis (AS) is a progressive, chronic, inflammatory skeletal disorder affecting the spine and sacroiliac joints. To date, the disease etiology remains unclear. Some studies have shown that T lymphocytes play important roles in the inflammatory process of AS, but imbalances in the numbers and functions of CD4+T cells and regulatory cells (Treg) in different differentiation stages are rarely mentioned. Tumornecmsis factor (TNF)-α blocker has been very effective in the treatment of ankylosing spondylitis, but its specific mechanism in the immune function of ankylosing spondylitis in active stage has not been fully revealed. <h3>Objectives:</h3> To investigate the role of Treg and CD4+T cells of different differentiation stages on the pathogenesis of active AS, and to study the machanism of TNF-α blocker on the treatment of active AS by detecting the number of Treg cells and CD4+T cells before and after the treatment. <h3>Methods:</h3> Ankylosing Spondylitis Disease Activity Score (ASDAS) was used to assess disease activity. AS patients who fulfilled the Assessment in Ankylosing Spondylitis Criteria in 1984 and ASDAS≥1.3 were enrolled in this study. The patients received subcutaneous injection of recombinant human tumor necrosis factor receptor-Fc fusion protein (rh TNFR-Fc) 50 mg weekly for 12 weeks. Healthy age and gender-matched subjects were also enrolled as control group. Flow cytometry analyses were carried out to detect the levels of a series of lymphocytes including different stages of differentiation CD4+T cells and Treg cells. C-reactive protein(CRP) levels in serum were determined by immunoturbidimetry. <h3>Results:</h3> A total of 23 active AS patients(Age: 31.74±10.20 yrs, M/F:19/4) and 50 healthy subjects (Age: 34.66±9.72 yrs, M/F: 45/15) were included in the study. The percentage of initialization CD4+T cells(CD3+CD4+CD45RA+CCR7+) and central memory CD4+T cells (CD3+CD4+CD45RA-CCR7+) were found to be significantly higher in the AS groups compared with the healthy individuals (P &lt; 0.05). However, the percentage of and Treg cells (CD3+CD4+CD25+CD127-) were significantly lower in the AS groups (P &lt; 0.05). After 12 weeks rh TNFR-Fc treatment, the percentage of initialization CD4+T cells and central memory CD4+T cells are significantly reduced. In contrast, the proportion of Treg cells increased significantly. <h3>Conclusion:</h3> Initialization CD4+T cells (CD3+CD4+CD45RA+CCR7+), central memory CD4+T cells (CD3+CD4+CD45RA-CCR7+) and Treg cells (CD3+CD4+CD25+CD127-) may play a role in the pathogenesis of AS. The down regulation of initialization CD4+T cells and central memory, and the up regulation of Treg cells in active AS patients are significant for the evaluation of the curative effect of rhTNFR-Fc. <h3>References</h3> [1] Croft M: The TNF family in T cell differentiation and function-unanswered questions and future directions. Semin Immunol2014; 26: 183-190. [2] Dulic S: The Impact of Anti-TNF Therapy on CD4+ and CD8+ Cell Subsets in Ankylosing Spondylitis. Pathobiology2018;85:201–210. [3] Zhongliang Duan: The immune dysfunction in ankylosing spondylitis patients. BioScience Trends. 2017; 11(1):69-76. <h3>Disclosure of Interests:</h3> None declared