补体成分C4的拷贝数变异与白塞病相关，但与伴急性前葡萄膜炎的强直性脊柱炎无关。
Copy number variations of complement component C4 are associated with Behçet's disease but not with ankylosing spondylitis associated with acute anterior uveitis.
作者信息
Hou Shengping, Qi Jian, Liao Dan, Zhang Qi, Fang Jing, Zhou Yan, Liu Yunjia, Bai Lin, Zhang Meifen, Kijlstra Aize, Yang Peizeng
机构信息
The First Affiliated Hospital of Chongqing Medical University, Chongqing Eye Institute, and Chongqing Key Laboratory of Ophthalmology, Chongqing, China.
出版信息
Arthritis Rheum. 2013 Nov;65(11):2963-70. doi: 10.1002/art.38116.
OBJECTIVE
Complement component C4 copy number variations are associated with various inflammatory diseases. This study was undertaken to investigate whether copy number variations of C4 are also involved in the pathogenesis of Behçet's disease (BD).
METHODS
Gene expression was examined by enzyme-linked immunosorbent assay (ELISA) or real-time polymerase chain reaction (PCR). Copy number variations of C4 isotypes (C4A and C4B) were detected by real-time PCR in 905 patients with BD, 205 patients with ankylosing spondylitis (AS) and acute anterior uveitis, and 1,238 controls. The activation of CD4+ T cells was analyzed by flow cytometry, and cytokine production was detected by ELISA.
RESULTS
Protein expression of total C4 in serum was significantly increased in patients with active BD compared with those with inactive BD or controls (Bonferroni corrected P [Pcorr ] = 1.64 × 10(-4) and Pcorr = 0.037, respectively), but not in patients with AS and acute anterior uveitis. Copy number variation analysis identified a significantly increased frequency of more than 2 copies of C4A in BD patients (P = 1.65 × 10(-7) , odds ratio [OR] 2.84). HLA-B51, which is located on the same chromosome as C4, showed a strong association with BD in the Han Chinese population (P = 8.90 × 10(-65) , OR 5.05), but logistic regression showed that C4A copy number variation was an independent risk factor for BD. A significantly increased expression of C4A was observed in the high copy number groups (>2 copies or 2 copies) versus the low copy number group (Pcorr = 0.019 and Pcorr = 0.044, respectively). Increased production of interleukin-6 (IL-6) was also observed in the high C4A copy number group (Pcorr = 0.037). No effect of C4 copy number variation on the expression of T cell activation markers was detected.
CONCLUSION
Our findings indicate that a high copy number of C4A confers risk for BD by modulating the expression of C4A and enhancing IL-6 production.
目的
补体成分C4拷贝数变异与多种炎症性疾病相关。本研究旨在调查C4拷贝数变异是否也参与白塞病（BD）的发病机制。
方法
通过酶联免疫吸附测定（ELISA）或实时聚合酶链反应（PCR）检测基因表达。采用实时PCR检测905例BD患者、205例强直性脊柱炎（AS）和急性前葡萄膜炎患者以及1238例对照者中C4同种型（C4A和C4B）的拷贝数变异。通过流式细胞术分析CD4+T细胞的活化情况，并通过ELISA检测细胞因子的产生。
结果
与非活动期BD患者或对照者相比，活动期BD患者血清中总C4的蛋白表达显著增加（Bonferroni校正P值[Pcorr]分别为1.64×10⁻⁴和Pcorr = 0.037），但AS和急性前葡萄膜炎患者中未出现这种情况。拷贝数变异分析发现，BD患者中C4A超过2拷贝的频率显著增加（P = 1.65×10⁻⁷，比值比[OR]为2.84）。与C4位于同一条染色体上的HLA - B51在汉族人群中与BD呈强关联（P = 8.90×10⁻⁶⁵，OR为5.05），但逻辑回归显示C4A拷贝数变异是BD的独立危险因素。与低拷贝数组相比，高拷贝数组（>2拷贝或2拷贝）中C4A的表达显著增加（Pcorr分别为0.019和Pcorr = 0.044）。在高C4A拷贝数组中也观察到白细胞介素 - 6（IL - 6）产生增加（Pcorr = 0.037）。未检测到C4拷贝数变异对T细胞活化标志物表达的影响。
结论
我们的研究结果表明，高拷贝数的C4A通过调节C4A的表达和增强IL - 6的产生赋予BD发病风险。
Zotero 插件