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FRI0008 IL-21 regulates B cell proliferation and differentiation in rheumatoid arthritis
  1. R. Liu,
  2. Q. Wu,
  3. X. Li,
  4. L. Sun
  1. The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China

Abstract

Background Interleukin (IL)-21 is a member of type I cytokine family. Recent studies have indicated that IL-21 is an important regulator for human B cell activation, proliferation, plasma cell (PC) differentiation, immunoglobulin (Ig) production and isotype switching. Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by abnormal production of cytokines and autoantibodies including rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP), suggesting that B cells play a key role in pathogenesis of RA.

Objectives The aim of this study was to investigate the effect of IL-21 on B cell proliferation and differentiation of RA patients.

Methods Concentrations of IL-21 in serum were measured by ELISA. The correlation between serum IL-21 levels and clinical features of RA patients were assessed. The percentages of IL-21R+CD19+ cells were analyzed by flow cytometry (FACS) in peripheral blood mononuclear cells (PBMC) from RA patients and healthy controls. PBMC from RA patients were stimulated with rIL-21 (50 or 100ng/ml) after motivation of anti-CD40 and anti-IgM. The percentages of IL-21R, activation markers (CD40, CD69 and CD25) on B cells and the proliferation labeled with CFSE as well as differentiation of B cells were determined by using FACS analysis

Results The results showed that serum IL-21 concentrations in RA patients (191.3±34.42pg/ml, n=104) were significantly higher than in healthy controls (10.33±11.43pg/ml, n=56, p<0.01). The levels of IL-21 in RA patients were positively related to RF-IgM (r=0.23, p<0.05), RF-IgA (r=0.34, p<0.05), RF-IgG (r=0.35, p<0.05) and anti-CCP (r=0.32, p<0.05). Moreover, the percentages of IL-21R+CD19+ cells were found to be markedly higher in PBMC of RA patients (48.55%±2.63%, n=50) compared to healthy controls (34.12%±2.37%, n=40, p<0.01) and IL-21 could up-regulate IL-21R expression on B cells in vitro. Meanwhile, IL-21 stimulated the proliferation of B cells and activated markers expressions (CD40, CD69 and CD25). IL-21 induced more production of CD138+CD19+/low cells in RA patients, indicating that IL-21 can promote B cell differentiation.

Conclusions These results suggest that increased IL-21 expression from RA patients might support B cells proliferation, activation and antibody secretion. Thus, antagonizing IL-21 may be a novel strategy for treating RA.

Disclosure of Interest None Declared

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