人巨细胞病毒UL95抗原表位肽段测定在SLE诊断中的意义  

The significance of detecting human cytomegalovirus UL95 antigenic epitope peptide in the diagnosis of SLE

作　　者：胡亚 徐臣玉 强薇 章慧娣[1] 冯方方 Hu Ya;Xu Chenyu;Qiang Wei;Zhang Huidi;Feng Fangfang(Nephrology Department,The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000,China;Basic Medical Major,School of Basic Medicine,Wenzhou Medical University,Wenzhou 325000,China;Clinical Medicine Major,the First Clinical School of Wenzhou Medical University,Wenzhou 325000,China;Morphology Teaching Experimental Center,School of Basic Medicine,Wenzhou Medical University,Wenzhou 325000,China)

机构地区：[1]温州医科大学附属第一医院肾内科,温州325000 [2]温州医科大学基础医学院,温州325000 [3]温州医科大学第一临床医学院,温州325000 [4]温州医科大学基础医学院形态教学实验中心,温州325000

出　　处：《中华检验医学杂志》2024年第9期1042-1051,共10页Chinese Journal of Laboratory Medicine

基　　金：国家自然科学基金(82001705)。

摘　　要：目的探讨人巨细胞病毒(HCMV)UL95基因的优势B细胞表位肽段在诊断系统性红斑狼疮(SLE)疾病中的临床意义,以及SLE患者血浆中UL95特异性抗体水平和临床指标的相关性,以期找到SLE疾病的辅助诊断指标。方法采用非随机对照研究,分析HCMV UL95基因序列特征及其多态性,并利用生物信息学分析并化学合成UL95优势B细胞表位短肽,将UL95合成短肽作为包被抗原,ELISA法检测97例SLE患者及35名健康对照者(HC)血浆中UL95的特异性抗体水平,ROC曲线分析UL95短肽抗体对于SLE的诊断价值,Pearson相关性检验分析UL95特异性抗体水平与SLE患者临床指标的相关性。结果UL95基因核苷酸序列相似性为92.9%~100%,氨基酸序列相似性为92.1%~100%,序列高度保守,具有同源性。多种参数综合预测得到可能优势B细胞表位6个,分别命名为(Bp1、Bp2、Bp3、Bp4、Bp5、Bp6)。ELISA结果显示SLE患者血浆中的UL95特异性抗体水平(0.35±0.12)高于HC组(0.28±0.10)(t=3.091,P=0.002)。区分SLE和HC的ROC曲线下面积为0.703,敏感度为54.6%,特异度为88.6%。此外中高活动亚组(SLEDAI≥4)的UL95特异性抗体水平(OD值)(0.36±0.10)高于低活动亚组(SLEDAI<4分)(0.30±0.07)(t=‒2.055,P=0.044)。UL95特异性抗体水平和临床指标总免疫球蛋白G、总免疫球蛋白M呈正相关,与补体C3、补体C4、血小板呈负相关。结论UL95的抗体水平与狼疮疾病活动度有关,UL95的Bp1(10~21)肽段对SLE辅助诊断有重要意义,有望成为一种新的参考指标。Objective To explore the clinical significance of the dominant B-cell epitope peptide of the human cytomegalovirus(HCMV)UL95 gene,as well as the correlation between the plasma UL95 specific antibody levels and clinical indicators in systemic lupus erythematosus(SLE)patients,in order to find auxiliary diagnostic indicators for SLE.Methods A non-randomized control study was conducted to analyze the sequencial characteristics and polymorphisms of HCMV UL95 gene,and bioinformatics analysis and chemical synthesis were used to synthesize UL95 dominant B cell epitope short peptides,which were used as coating antigens.Enzyme-linked immunosorbent assay(ELISA)assay was used to detect the specific antibody levels of plasma UL95 of 97 SLE patients and 35 healthy controls(HC).Receiver operating characteristic(ROC)curve analysis was used to evaluate the diagnostic value of UL95 short peptide antibodies for SLE diagnosis.Pearson correlation test was used to analyze the correlation between UL95 specific antibody levels and clinical indicators in SLE patients.Results The nucleotide sequence similarity of UL95 gene was 92.9%-100%,and the amino acid sequence similarity was 92.1%-100%,whose sequences were highly conserved and homologous.A comprehensive prediction of multiple parameters resulted in 6 possible dominant B cell epitopes,named(Bp1,Bp2,Bp3,Bp4,Bp5,Bp6)respectively.The ELISA results showed that the levels of plasma UL95 specific antibodies(0.35±0.12)in SLE patients were significantly higher than those of the HC group(0.28±0.10)(t=3.091,P=0.002).The area under the ROC curve for distinguishing SLE and HC was 0.703,with a sensitivity of 54.6%and a specificity of 88.6%.In addition,the UL95 specifific antibody levels(OD value)in the middle-high activity subgroup(systemic lupus erythematosus disease activity index,SLEDAI≥4)were higher(0.36±0.10)than those in the low activity subgroup(SLEDAI<4)(0.30±0.07)(t=‒2.055,P=0.044).UL95 specific antibody levels were positively correlated with clinical indicators such as total immu

关 键 词：巨细胞病毒 红斑狼疮 系统性 抗原 B细胞 

分 类 号：R593.241[医药卫生—内科学]