{"title":"BAFF 通过 NF-κB 通路参与 B 细胞活化,与类风湿性关节炎的疾病活动和骨质破坏有关","authors":"Ling-ling Zhang, Hui Xiao, Feng Zhang, Yu-jing Wu, Jin-ling Shu, Ying Li, Yu Tai, Sheng-qian Xu, Jian-hua Xu, Wei Wei","doi":"10.1038/s41401-020-00582-4","DOIUrl":null,"url":null,"abstract":"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, CD19+CD27+ B cells, CD19+CD20+CD27+ B cells, and CD19+CD20−CD27+ B cells) in the serum of RA patients were significantly increased compared with those of HCs. The percentages of CD19+BAFFR+ 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.","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":"42 10","pages":"1665-1675"},"PeriodicalIF":6.9000,"publicationDate":"2021-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/s41401-020-00582-4","citationCount":"11","resultStr":"{\"title\":\"BAFF, involved in B cell activation through the NF-κB pathway, is related to disease activity and bone destruction in rheumatoid arthritis\",\"authors\":\"Ling-ling Zhang, Hui Xiao, Feng Zhang, Yu-jing Wu, Jin-ling Shu, Ying Li, Yu Tai, Sheng-qian Xu, Jian-hua Xu, Wei Wei\",\"doi\":\"10.1038/s41401-020-00582-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"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, CD19+CD27+ B cells, CD19+CD20+CD27+ B cells, and CD19+CD20−CD27+ B cells) in the serum of RA patients were significantly increased compared with those of HCs. The percentages of CD19+BAFFR+ 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. 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引用次数: 11
摘要
TNF 家族 B 细胞活化因子(BAFF)是 TNF 配体超家族的成员之一,在 B 细胞的平衡、增殖、成熟和存活中起着关键作用。本研究检测了类风湿性关节炎(RA)患者体内的 BAFF 水平、BAFF 受体和 NF-κB 通路中重要分子的表达,并分析了 BAFF 水平与临床变量、实验室参数或 X 光评分之间的相关性,以期阐明 BAFF 在 RA 中的作用。研究共纳入了 50 名 RA 患者和 50 名健康对照组(HCs)。结果表明,RA 患者血清中 BAFF 水平明显高于健康对照者,而且 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)的百分比明显高于健康对照者。与 HC 相比,RA 患者血清中 CD19+BAFFR+ B 细胞、CD19+ BCMA+ B 细胞和 CD19+ TACI+ B 细胞的百分比明显增加。NF-κB通路中的重要分子(MKK3、MKK6、p-P38、p-P65、TRAF2和p52)在RA患者中的表达明显高于HCs,但RA患者的p100水平低于HCs。血清 BAFF 水平与 C 反应蛋白、类风湿因子、疾病活动度评分(28 个关节)、关节肿胀计数、关节触痛计数和 X 光评分呈正相关。在体外用 BAFF 处理正常 B 细胞时,B 细胞亚群的百分比和 BAFF 受体的表达均显著上调。BAFF 还能促进 MKK3、MKK6、p-P38、p-P65、TRAF2 和 p52 的表达。总之,本研究表明,BAFF水平与RA的疾病活动性和骨破坏相关。BAFF通过NF-κB信号通路参与RA中B细胞的分化、增殖和活化,这表明BAFF可能是RA的理想治疗靶点。
BAFF, involved in B cell activation through the NF-κB pathway, is related to disease activity and bone destruction in rheumatoid arthritis
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, CD19+CD27+ B cells, CD19+CD20+CD27+ B cells, and CD19+CD20−CD27+ B cells) in the serum of RA patients were significantly increased compared with those of HCs. The percentages of CD19+BAFFR+ 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.
期刊介绍:
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