Background/Purpose: 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. 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 with 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 marker 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.

Conclusion: 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.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/il-21-regulates-b-cell-proliferation-and-differentiation-in-rheumatoid-arthritis/