Department of Rheumatology, University of Tromsø, Tromsø, Norway.
Rheumatology (Oxford). 2011 Dec;50(12):2197-205. doi: 10.1093/rheumatology/ker282. Epub 2011 Oct 8.
To determine whether increased levels of B-cell activating factor (BAFF) in patients with SLE are due to disease activity or genetic variations in the promoter region of the BAFF gene and BAFF gene expression.
The case-control study included 101 SLE patients and 111 healthy controls. Five single nucleotide polymorphisms (SNPs) in the BAFF promoter region were investigated by melting point analysis: c.-2841 (T > C), c.-2704 (T > C), c.-2701 (A > T), c.-871 (C > T) and c.-514 (A > G). BAFF mRNA levels were determined by real-time PCR (BAFF-RQ) and serum BAFF (s-BAFF) levels were measured by ELISA. Independent predictors that might be correlated with increased s-BAFF in SLE patients were analysed by multivariate regression methods. RESULTS; Although s-BAFF levels were increased in SLE patients (1.73 vs 0.98 ng/μl, P < 0.001), no specific BAFF genotype was found to associate with SLE. The different genotypes defined by the investigated SNPs were identified both in SLE patients and healthy controls with similar frequencies. No association was found between BAFF genotype and BAFF-RQ. s-BAFF was independent of other factors, correlated with CRP (β = 0.40, P < 0.001) and physician's visual analogue score (R = 0.21, P = 0.046) and inversely with haemoglobin (β = -0.32, P < 0.001) and IgA (β = -0.33, P = 0.001).
Increased s-BAFF levels in SLE patients are associated with the acute-phase responses, CRP and haemoglobin, but probably not dependent on BAFF genotype or expression. This indicates that s-BAFF production occurs at sites of inflammation.
确定系统性红斑狼疮(SLE)患者中 B 细胞激活因子(BAFF)水平升高是由于疾病活动还是 BAFF 基因启动子区域的遗传变异和 BAFF 基因表达。
这项病例对照研究纳入了 101 例 SLE 患者和 111 名健康对照者。通过熔点分析检测 BAFF 启动子区域的 5 个单核苷酸多态性(SNP):c.-2841(T>C)、c.-2704(T>C)、c.-2701(A>T)、c.-871(C>T)和 c.-514(A>G)。通过实时 PCR(BAFF-RQ)测定 BAFF mRNA 水平,通过 ELISA 测定血清 BAFF(s-BAFF)水平。采用多元回归方法分析可能与 SLE 患者 s-BAFF 升高相关的独立预测因子。结果:尽管 SLE 患者的 s-BAFF 水平升高(1.73 vs 0.98ng/μl,P<0.001),但未发现特定的 BAFF 基因型与 SLE 相关。在所研究的 SNP 定义的不同基因型在 SLE 患者和健康对照者中均有发现,且频率相似。BAFF 基因型与 BAFF-RQ 之间无关联。s-BAFF 是其他因素的独立相关因素,与 CRP(β=0.40,P<0.001)和医生的视觉模拟评分(R=0.21,P=0.046)呈正相关,与血红蛋白(β=-0.32,P<0.001)和 IgA(β=-0.33,P=0.001)呈负相关。结论:SLE 患者 s-BAFF 水平升高与急性期反应、CRP 和血红蛋白有关,但可能不依赖于 BAFF 基因型或表达。这表明 s-BAFF 的产生发生在炎症部位。