Institute of Clinical Pharmacology, Anhui Medical University/Key Laboratory of Anti-inflammatory and Immunopharmacology of Education Ministry of China/Anti-inflammatory Immune Drugs Collaborative Innovation Center of Anhui Province, Hefei, 230032, China.
Department of Rheumatology and Immunology, No. 1 Affiliated Hospital, Anhui Medical University, Hefei, 230032, China.
Acta Pharmacol Sin. 2021 Oct;42(10):1665-1675. doi: 10.1038/s41401-020-00582-4. Epub 2021 Jan 22.
B cell activating factor of TNF family (BAFF) is a member of TNF ligand superfamily and plays a key role in B cell homeostasis, proliferation, maturation, and survival. In this study, we detected BAFF level, the expressions of BAFF receptors and important molecules in NF-κB pathway in rheumatoid arthritis (RA) patients and analyzed the correlation between BAFF level and clinical variables, laboratory parameters or X-ray scores in order to elucidate the roles of BAFF in RA. A total of 50 RA patients and 50 healthy controls (HCs) were enrolled. We showed that the serum BAFF level in RA patients was significantly higher than that of HCs, and the percentages of B cell subsets (CD19 B cells, CD19CD27 B cells, CD19CD20CD27 B cells, and CD19CD20CD27 B cells) in the serum of RA patients were significantly increased compared with those of HCs. The percentages of CD19BAFFR B cells, CD19 BCMA B cells, and CD19 TACI B cells in RA patients were significantly increased compared with those in HCs. The expression of important molecules in the NF-κB pathway (MKK3, MKK6, p-P38, p-P65, TRAF2, and p52) was significantly higher in RA patients than in HCs, but p100 level in RA patients was lower than that in HCs. The serum BAFF level was positively correlated with C-reactive protein, rheumatoid factor, disease activity score (in 28 joints), swollen joint counts, tender joint counts, and X-ray scores. When normal B cells were treated with BAFF in vitro, the percentages of the B cell subset and the expression of BAFF receptors were significantly upregulated. BAFF also promoted the expression of MKK3, MKK6, p-P38, p-P65, TRAF2, and p52. In conclusion, this study demonstrates that BAFF level is correlated with the disease activity and bone destruction of RA. BAFF is involved in the differentiation, proliferation, and activation of B cells in RA through NF-κB signaling pathway, suggesting that BAFF might be an ideal therapeutic target for RA.
B 细胞激活因子（BAFF）属于肿瘤坏死因子配体超家族成员，在 B 细胞的自身稳定、增殖、成熟和存活中发挥关键作用。本研究检测了类风湿关节炎（RA）患者血清 BAFF 水平及其受体和 NF-κB 通路相关重要分子的表达，并分析了 BAFF 水平与临床变量、实验室参数或 X 射线评分之间的相关性，旨在阐明 BAFF 在 RA 中的作用。共纳入 50 例 RA 患者和 50 例健康对照者（HCs）。结果显示，RA 患者血清 BAFF 水平显著高于 HCs，RA 患者血清中 B 细胞亚群（CD19+B 细胞、CD19+CD27+B 细胞、CD19+CD20+CD27+B 细胞和 CD19+CD20+CD27+B 细胞）的比例明显高于 HCs。RA 患者 CD19+BAFFR+B 细胞、CD19+BCMA+B 细胞和 CD19+TACI+B 细胞的比例明显高于 HCs。RA 患者 NF-κB 通路重要分子（MKK3、MKK6、p-P38、p-P65、TRAF2 和 p52）的表达明显高于 HCs，但 RA 患者 p100 水平低于 HCs。血清 BAFF 水平与 C 反应蛋白、类风湿因子、疾病活动评分（28 个关节）、肿胀关节数、压痛关节数和 X 射线评分呈正相关。体外用 BAFF 处理正常 B 细胞后，B 细胞亚群比例和 BAFF 受体表达明显上调。BAFF 还促进了 MKK3、MKK6、p-P38、p-P65、TRAF2 和 p52 的表达。总之，本研究表明，BAFF 水平与 RA 的疾病活动度和骨破坏有关。BAFF 通过 NF-κB 信号通路参与 RA 中 B 细胞的分化、增殖和激活，提示 BAFF 可能是 RA 的理想治疗靶点。
