BAFF, involved in B cell activation through the NF-κB pathway, is related to disease activity and bone destruction in rheumatoid arthritis  

作　　者：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 

机构地区：[1]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 [2]Department of Rheumatology and Immunology,No.1 Affiliated Hospital,Anhui Medical University,Hefei 230032,China

出　　处：《Acta Pharmacologica Sinica》2021年第10期1665-1675,共11页中国药理学报（英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation of China(No.U1803129,81803538,81302517 and 81330081).

摘　　要：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.

关 键 词：rheumatoid arthritis B cell BAFF disease activity CORRELATION BIOMARKER 

分 类 号：R593.22[医药卫生—内科学] R96[医药卫生—临床医学]