Zheng Nuoyan, Fan Jinjin, Wang Bing, Wang Dongxian, Feng Pinning, Yang Qiongqiong, Yu Xueqing
Translational Medical Center, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510000, P.R. China.
Department of Nephrology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510000, P.R. China.
Mol Med Rep. 2017 Apr;15(4):1925-1935. doi: 10.3892/mmr.2017.6190. Epub 2017 Feb 10.
B cells are critically important for the pathogenesis of IgA nephropathy (IgAN). The present study aimed to investigate the abundance of B cell activating factor (BAFF), which belongs to the tumor necrosis factor superfamily, in the peripheral blood of patients with IgAN. The different forms of BAFF in peripheral blood and its association with clinical features and immunological factors were analyzed. mRNA levels of BAFF and other associated genes in the peripheral blood mononuclear cells (PBMCs) of patients with IgAN and controls were analyzed by quantitative polymerase chain reaction. Cellular BAFF proteins in PBMCs and plasma soluble BAFF proteins were measured by western blot analysis and ELISA, respectively. PBMCs from patients were stimulated with Streptococcus pyogenes (S. pyogenes) ex vivo for the BAFF secretion assay. The data demonstrated that, although mRNA levels of BAFF in PBMC were not significantly increased in patients with IgAN, they were positively associated with those of a proliferation inducing ligand (APRIL), Toll‑like receptor (TLR)2, TLR4 and TLR7. The cellular BAFF protein in PBMCs was not upregulated. Plasma BAFF protein levels in patients with IgAN (n=76) were significantly decreased compared with controls. However, plasma BAFF levels were positively associated with serum creatinine, proteinuria, uric acid and group A Streptococcus infection index in patients with IgAN. In patients with IgAN, plasma BAFF concentrations were markedly higher in those with more severe renal tubular atrophy/interstitial fibrosis and global glomerulosclerosis. Furthermore, BAFF production in PBMCs of patients with IgAN was increased following S. pyogenes stimulation ex vivo. In conclusion, plasma BAFF levels in patients with IgAN were associated with renal function and disease activity. S. pyogenes infection was closely associated with BAFF production in patients with IgAN.
B细胞对IgA肾病（IgAN）的发病机制至关重要。本研究旨在调查属于肿瘤坏死因子超家族的B细胞活化因子（BAFF）在IgAN患者外周血中的丰度。分析了外周血中不同形式的BAFF及其与临床特征和免疫因素的关联。通过定量聚合酶链反应分析了IgAN患者和对照组外周血单个核细胞（PBMC）中BAFF及其他相关基因的mRNA水平。分别通过蛋白质免疫印迹分析和酶联免疫吸附测定法检测PBMC中的细胞BAFF蛋白和血浆可溶性BAFF蛋白。对患者的PBMC进行体外化脓性链球菌（S. pyogenes）刺激以进行BAFF分泌测定。数据表明，虽然IgAN患者PBMC中BAFF的mRNA水平没有显著升高，但它们与增殖诱导配体（APRIL）、Toll样受体（TLR）2、TLR4和TLR7的mRNA水平呈正相关。PBMC中的细胞BAFF蛋白未上调。与对照组相比，IgAN患者（n = 76）的血浆BAFF蛋白水平显著降低。然而，IgAN患者的血浆BAFF水平与血清肌酐、蛋白尿、尿酸和A组链球菌感染指数呈正相关。在IgAN患者中，肾小管萎缩/间质纤维化和全球肾小球硬化更严重的患者血浆BAFF浓度明显更高。此外，体外化脓性链球菌刺激后，IgAN患者PBMC中的BAFF产生增加。总之，IgAN患者的血浆BAFF水平与肾功能和疾病活动相关。化脓性链球菌感染与IgAN患者的BAFF产生密切相关。
