| Objective:To detect serum IL-21and IL-21R mRNA levels on peripheral blood mononuclear cell (PBMC) of patients with rheumatoid arthritis (RA) and analyze their clinical significance and explore the effect of IL-21on the activation, proliferation and differentiation of B cells.Methods:The serum from76RA patients and37health controls were selected. Serum IL-21levels were detected by enzyme-linked immunosorbent assay (ELISA). The correlations between serum IL-21levels and clinical and laboratory parameters of RA patients were investigated. Real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to detect IL-21R mRNA expression on PBMC from RA patients and health controls.The percentages of IL-21R expression and activated marker (CD69), proliferation, and differentiation of B cells were analyzed by flow cytometry. Production of IgG and IgM in culture supernatant was tested by ELISA. Paired or unpaired t test, Mann-Whitney U test or one way ANOVA and spearman’s rank correlation test were used for statistical analysis with software SPSS17.0.Results:Serum IL-21levels in RA patients (131.0±156.2pg/ml) were significantly higher than that of the health controls[(67.1±29.1)pg/ml,(J=957.5, P=0.006)]. In rheumatoid factor (RF)-IgM, RF-IgA, RF-IgG and anti-cyclic citrullinated peptide antibodies(anti-CCP) positive groups, serum IL-21levels in RA patients were positively correlated with these antibodies (r=0.300,0.382,0.370,0.372, P<0.05). Serum IL-21levels were remarkably higher in RF-IgM, RF-IgA, RF-CCP positive groups than in the negative ones[(166.9±197.7) pg/ml vs(75.9±25.0) pg/ml, U=176.5, P=0.024;(168.6±185.2) pg/ml vs(78.9±34.8) pg/ml, U=282.5, P=0.016;(180.5±197.4) pg/ml vs(87.2±39.5) pg/ml, U=333.0, P=0.031].Also, serum IL-21levels in RA patients were positively correlated with tenderness of joint number in28joints (TEN28) and swelling of joint number in28joints (SW28)(r=0.342;0.200, P<0.05). However, serum IL-21levels in RA patients were no significantly correlation with DAS28, C-reaction protein, erythrocyte sedimentation rate, age or duration. The expression of IL-21R mRNA on PBMC in RA patients was significantly higher than the health controls[(1.5±0.7) vs (1.1±0.3), U=412.0, P=0.044)]. The percentage of both IL-21R and CD19positive cells in periphral blood of RA patients was remarkably higher than that of health controls[(54.9±1.8)%vs(37.8±1.4)%, U=407.0, P<.001]. In vitro, rIL-21was able to up-regulate IL-21R expression on B cells. Meanwhile, the ability of rIL-21to promote activated marker expression (CD69) on B cells and proliferation of B cells in RA was more powerful than health controls, which could be correspondently reversed by anti-IL-21R. Finally, IL-21was more inclined to induce differentiation of B cells into plasmablasts and IgG secretion were higher in RA than health controls[(353.7±131.0)ng/ml vs(297.2±110.8)ng/ml,t=4.1, P=0.006] after activation with anti-CD40and anti-IgM.Conclusion:IL-21and IL-21R were highly expressed in RA patients, and IL-21was positively correlated with some antibodies, such as RF, anti-CCP antibody. The activation, proliferation and differentiation of B cells and its secretion of immunoglobulins can be promoted by rIL-21, indicating that IL-21could be a part link of the pathogenesis of RA. |
PDF Full Text Request