伴CD11b突变的SLE患者干扰素诱导基因的表达研究

IFN-stimulated gene expression in SLE patients with CD11b mutation

为探讨SLE患者CD11b rs1143679突变与WT的临床特征及干扰素诱导基因(IFN-stimulated gene,ISG)的表达差异,收集1193例SLE患者,进行CD11b rs1143679单核苷酸多态性检测,分析其临床表现;采用荧光定量PCR检测突变和部分WT患者IFIT1、IFIT4、ISG15在mRNA和蛋白质水平的表达,1193例患者CD11b突变频率为1.84%(n=22)。结果显示,两组患者蛋白尿的发生差异具有统计学意义(P=0.032),其中突变患者24h尿蛋白值为(0.61±0.18)g;WT患者为(0.39±0.14)g(P=0.034);突变患者发生肾损伤的概率为68.2%,较WT患者显著增加(47.3%)(P=0.042);突变患者补体C3水平也较WT患者明显降低(P=0.021)。CD11b突变患者PBMC中IFIT1(P=0.025)、IFIT4(P=0.031)、ISG15(P=0.030)mRNA水平明显高于WT患者并与蛋白尿的发生呈正相关,其蛋白质相对表达量显著高于WT患者(P<0.05)。综上,CD11b突变的SLE患者肾损伤风险增加,ISG表达上调,可能在SLE发生发展中发挥重要作用。

To investigate the difference between SLE patients with CD11b rs1143679 mutant and patients with WT CD11b in typeⅠIFN-stimulated gene(ISG)expression and clinical characteristics of SLE,we collected 1193 SLE patients and performed CD11b rs1143679 single nucleotide polymorphism typing.We analyzed the clinical phenotypes,conducted real-time PCR to measure IFIT1,IFIT4,ISG15 mRNA and their protein expression.Among the 1193 patients,the frequency of CD11b mutation was 1.84%(n=22).The results showed that there was significant difference in proteinuria between the two groups(P=0.032).The 24 hurine protein value of the mutant patients was(0.61±0.18)g while the WT patients was(0.39±0.14)g(P=0.034).The possibility of renal injury in the mutant group was 68.2%,significantly different from that of non-mutant group(P=0.042).Compared with WT group,complement component C3 level was significantly reduced in mutant patients(P=0.021).The mRNA levels of IFIT1(P=0.025),IFIT4(P=0.031)and ISG15(P=0.030)in PBMC of CD11b mutant patients were higher than those of WT patients.Moreover,the relative protein expression levels of IFIT1,IFIT4 and ISG15 were also significantly higher than those of WT patients.In conclusion,SLE patients with CD11b mutation have an increased risk of renal injury and up-regulated expression of ISG,which may play an important role in the development of SLE.