Research Institute of Biomedical Sciences (IICB), University Center for Health Sciences, University of Guadalajara, Sierra Mojada 950, Edificio Q, Primer Piso, CP 44340, Guadalajara, Jalisco, Mexico.
Biomedical Sciences, University Center for Health Sciences, University of Guadalajara, Guadalajara, Mexico.
Clin Exp Med. 2019 May;19(2):183-190. doi: 10.1007/s10238-019-00549-8. Epub 2019 Feb 11.
B cell-activating factor (BAFF) promotes the survival, proliferation and maturation of B lymphocytes, which are key elements in the pathogenesis of systemic lupus erythematosus (SLE). This cytokine is encoded on TNFSF13B gene, and diverse single-nucleotide polymorphisms have been associated with susceptibility in different autoimmune disorders. In this study, the relationship of TNFSF13B gene rs9514827T>C, rs1041567T>A and rs9514828C>T polymorphisms, mRNA expression and soluble BAFF levels was investigated in 175 SLE patients and 208 healthy controls (HC). The TNFSF13B polymorphisms were evaluated by PCR-RFLP technique. The TNFSF13B gene expression was quantified through the RT-PCR assays. The soluble BAFF (sBAFF) levels were measured with ELISA test. There were no differences in genotype and allele frequencies for the three TNFSF13B polymorphisms, between SLE patients and HC. SLE patients showed 3.15-fold more TNFSF13B gene expression than HC. The patients who displayed most mRNA expression were those with active disease and the carriers of rs9514828 T variant allele. The sBAFF serum levels were higher in SLE patients compared to HC (2.083 vs. 0.742 ng/mL, p < 0.001). The SLE patients with active disease showed the higher sBAFF serum levels (2.403 ng/mL), mainly patients with lupus nephritis and hematological manifestations. In addition, a correlation of sBAFF with disease activity was found (r = 0.32, p < 0.001). In conclusion, the TNFSF13B gene polymorphisms were not found to be associated with SLE susceptibility in Mexican mestizos. Nevertheless, rs9514828C>T polymorphism seems to increase TNFSF13B gene expression. High BAFF expression is related to active disease, renal and hematological involvement; therefore, it could be considered as follow-up biomarker in SLE patients.
B 细胞激活因子 (BAFF) 可促进 B 淋巴细胞的存活、增殖和成熟，B 淋巴细胞是系统性红斑狼疮 (SLE) 发病机制中的关键因素。这种细胞因子编码在 TNFSF13B 基因上，不同的单核苷酸多态性与不同自身免疫性疾病的易感性有关。在这项研究中，研究人员调查了 175 名 SLE 患者和 208 名健康对照者 (HC) 的 TNFSF13B 基因 rs9514827T>C、rs1041567T>A 和 rs9514828C>T 多态性、mRNA 表达和可溶性 BAFF 水平之间的关系。通过 PCR-RFLP 技术评估 TNFSF13B 多态性。通过 RT-PCR 检测 TNFSF13B 基因的表达。通过 ELISA 试验测量可溶性 BAFF (sBAFF) 水平。SLE 患者与 HC 之间的三个 TNFSF13B 多态性的基因型和等位基因频率没有差异。SLE 患者的 TNFSF13B 基因表达是 HC 的 3.15 倍。mRNA 表达最多的患者是那些患有活动期疾病和 rs9514828 T 变异等位基因的患者。与 HC 相比，SLE 患者的血清 sBAFF 水平更高 (2.083 vs. 0.742 ng/mL，p < 0.001)。患有活动期疾病的 SLE 患者显示出更高的血清 sBAFF 水平 (2.403 ng/mL)，主要是狼疮肾炎和血液学表现的患者。此外，还发现 sBAFF 与疾病活动度相关 (r = 0.32，p < 0.001)。总之，在墨西哥梅斯蒂索人中，TNFSF13B 基因多态性与 SLE 易感性无关。然而，rs9514828C>T 多态性似乎增加了 TNFSF13B 基因的表达。高 BAFF 表达与活动期疾病、肾脏和血液学受累有关；因此，它可以被视为 SLE 患者的随访生物标志物。
