Cai Xiao-Yu, Zhu Yue, Wang Chen, Tang Xiao-Yu, Han Le, Shu Jin-Ling, Zhang Xian-Zheng, Liang Fa-Qin, Ge Jing-Ru, Xu Li, Mei Dan, Zhang Ling-Ling, Wei Wei
Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China.
Front Pharmacol. 2020 May 12;11:676. doi: 10.3389/fphar.2020.00676. eCollection 2020.
To explore the role of B cells in rheumatoid arthritis (RA) and the potential effects and mechanisms of etanercept on B cells.
In RA patients, the levels of tumor necrosis factor-α (TNF-α) and B cell activating factor (BAFF) were detected by ELISA. The percentage of B cell subsets was measured by flow cytometry. Laboratory indicators (rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate) and clinical indicators (disease activity score in 28 joints, health assessment questionnaire score, swollen joint counts, tender joint counts) were measured. The correlation between B cell subsets and laboratory indicators or clinical indicators was analyzed. In mice, B cells proliferation was detected by CCK-8 kit. The expression of TNFRII and the percentage of B cell subsets in spleen were detected by flow cytometry. The expressions of TRAF2, p38, P-p38, p65, P-p65 in B cells were detected by WB.
The percentage of CD19CD27CD138 plasma B cells was positively correlated with ESR or RF. Etanercept could decrease the percentage of CD19 total B cells, CD19CD27 memory B cells and CD19CD27CD138 plasma B cells, reduce the levels of TNF-α, BAFF, relieve clinical and laboratory indicators in RA patients. In addition, etanercept could inhibit the proliferation of B cells, bate the differentiation of transitional B cells to mature B cells, down-regulate the expression of TNFRII, TRAF2, P-p38, P-p65 in B cells.
B cells act a key role in the pathogenesis of RA. Etanercept inhibits B cells differentiation by down-regulating TNFRII/TRAF2/NF-κB signaling pathway.
探讨B细胞在类风湿关节炎（RA）中的作用以及依那西普对B细胞的潜在影响及机制。
采用酶联免疫吸附测定法（ELISA）检测RA患者肿瘤坏死因子-α（TNF-α）和B细胞活化因子（BAFF）水平。采用流式细胞术检测B细胞亚群百分比。检测实验室指标（类风湿因子、C反应蛋白、红细胞沉降率）和临床指标（28个关节疾病活动评分、健康评估问卷评分、肿胀关节计数、压痛关节计数）。分析B细胞亚群与实验室指标或临床指标之间的相关性。在小鼠中，采用CCK-8试剂盒检测B细胞增殖。采用流式细胞术检测脾脏中TNFRII表达及B细胞亚群百分比。采用蛋白质免疫印迹法（WB）检测B细胞中TRAF2、p38、磷酸化p38（P-p38）、p65、磷酸化p65（P-p65）的表达。
CD19CD27CD138浆细胞B细胞百分比与红细胞沉降率或类风湿因子呈正相关。依那西普可降低CD19总B细胞、CD19CD27记忆B细胞和CD19CD27CD138浆细胞B细胞百分比，降低TNF-α、BAFF水平，缓解RA患者的临床和实验室指标。此外，依那西普可抑制B细胞增殖，抑制过渡性B细胞向成熟B细胞分化，下调B细胞中TNFRII、TRAF2、P-p38、P-p65的表达。
B细胞在RA发病机制中起关键作用。依那西普通过下调TNFRII/TRAF2/核因子κB（NF-κB）信号通路抑制B细胞分化。
