流式点阵免疫发光法检测抗染色质抗体在结缔组织病诊断中的价值

doi:10.3969/j.issn.1673-8640.2019.11.014

检验医学 ›› 2019, Vol. 34 ›› Issue (11): 1021-1025.DOI: 10.3969/j.issn.1673-8640.2019.11.014

• 技术研究与评价·论著 • 上一篇下一篇

流式点阵免疫发光法检测抗染色质抗体在结缔组织病诊断中的价值

王娟¹, 沈青莹¹, 王楷文², 赵江峰²

1.上海交通大学附属第一人民医院检验科,上海 200080
2.上海交通大学医学院附属仁济医院南院风湿科,上海 201112

收稿日期:2019-06-05 出版日期:2019-11-30 发布日期:2019-12-05
作者简介:null
作者简介：王娟,女,1985年生,硕士,技师,主要从事免疫学检验工作。沈青莹,女,1984年生,学士,技师,主要从事免疫学检验工作。王娟和沈青莹对本研究具有同等贡献,并列为第一作者。
基金资助:
2018年度上海市“医苑新星”青年医学人才培养资助计划-临床检验项目;上海申康医院发展中心临床辅助科室能力建设项目（SHDC22014005）

Role of anti-chromatin antibody determined by automatic multiplex bead immunoassay in the diagnosis of connective tissue diseases

WANG Juan¹, SHEN Qingying¹, WANG Kaiwen², ZHAO Jiangfeng²

1.Department of Clinical Laboratory,Shanghai General Hospital,Shanghai Jiaotong University,Shanghai 200080,China
2.Department of Rheumatology,South Campus,Renji Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 201112,China

Received:2019-06-05 Online:2019-11-30 Published:2019-12-05

摘要/Abstract

摘要：

目的探讨流式点阵免疫发光法检测抗染色质抗体在结缔组织病诊断中的价值。方法采用流式点阵免疫荧光法检测384例结缔组织病患者[系统性红斑狼疮（SLE）243例、多肌炎（PM）39例、混合性结缔组织病（MCTD）15例、干燥综合征（SS）51例、系统性硬化症（SSc）7例、类风湿关节炎（RA）29例]、200例非风湿病患者（疾病对照组）、200名体检正常者（正常对照组）血清抗染色质抗体的表达,同时采用酶联免疫吸附试验（ELISA）检测抗双链DNA（dsDNA）抗体、抗组蛋白抗体及抗核小体抗体,采用间接免疫荧光法检测抗核抗体（ANA）。采用Spearman相关分析评估系统性红斑狼疮疾病活动度指数（SLEDIA）评分与抗染色质抗体的相关性。采用受试者工作特征（ROC）曲线分析各项指标诊断SLE的价值。结果正常对照组、疾病对照组、SLE组、MCTD组、PM组、SS组、SSc组及RA组抗染色质抗体阳性率分别为0.00%、1.00%、70.78%、73.33%、23.08%、17.65%、28.57%及10.34%。抗染色质抗体阳性率随ANA滴度的增高而增高。将MCTD组、PM组、SS组、SSc组及RA组归为非SLE组,SLE组血清抗染色质抗体水平显著高于非SLE组（P<0.000 1）。SLE组中抗染色质抗体、抗dsDNA抗体、抗核小体抗体和抗组蛋白抗体中仅单个抗体阳性而其他3种抗体均阴性的比例分别为 45.39%、32.34%、13.42%和7.37%,4种抗体之间均有一定比例的交叉阳性。抗核小体抗体、抗染色质抗体、抗dsDNA抗体及抗组蛋白抗体诊断SLE ROC曲线的曲线下面积（AUC）分别为0.813、0.779、0.777及0.613。抗染色质抗体与SLEDAI评分无相关性（r=0.124 6,P=0.177 0）。SLE患者未合并肾炎者与合并肾炎者之间血清抗染色质抗体水平差异无统计意义（P>0.05）。结论流式点阵免疫荧光法检测抗染色质抗体在结缔组织病诊断中有一定的临床价值。

关键词: 抗染色质抗体, 流式点阵免疫发光法, 结缔组织病

Abstract:

Objective To investigate the role of anti-chromatin antibody determined by automatic multiplex bead immunoassay in the diagnosis of connective tissue diseases. Methods The expressions of anti-chromatin antibody in 384 patients with connective tissue diseases [243 cases of systemic lupus erythematosus（SLE）,39 cases of polymyositis（PM）,15 cases of mixed connective tissue disease（MCTD）,51 cases of Sjögen's syndrome（SS）,7 cases of systemic sclerosis（SSc） and 29 cases of rheumatoid arthritis（RA）],200 non-rheumatic disease patients（disease control group） and 200 healthy subjects（healthy control group） were determined. Anti-double-stranded DNA（dsDNA） antibodies,anti-histone antibodies and anti-nucleosome antibodies were determined by enzyme-linked immunosorbent assay（ELISA）. Anti-nuclear antibodies（ANA） were determined by indirect immunofluorescence. The correlation between systemic lupus erythematosus disease activity index（SLEDAI） score and anti-chromatin antibody was evaluated. Receiver operating characteristic（ROC） curve was used to analyze the roles of these indicators for the diagnosis of SLE. Results The positive rates of anti-chromatin antibodies in healthy control,disease control,SLE,MCTD,PM,SS,SSc and RA groups were 0.00%,1.00%,70.78%,73.33%,23.08%,17.65%,28.57% and 10.34%,respectively. The positive rate of anti-chromatin antibodies increased with the increase of ANA titer. MCTD,PM,SS,SSc and RA groups were merged into non-SLE group. Serum anti-chromatin antibody level in SLE group was higher than that in non-SLE group（P<0.000 1）. For anti-chromatin antibody,anti-dsDNA antibody,anti-nucleosome antibody and anti-histone antibody in SLE group,the rates of single-antibody positive and the other 3-antibody negative was 45.39%,32.34%,13.42% and 7.37%,respectively. There were some cross-positive rates among the 4 antibodies. The areas under curves（AUC） of anti-nucleosome antibody,anti-chromatin antibody,anti-dsDNA antibody and anti-histone antibody for the diagnosis of SLE were 0.813,0.779,0.777 and 0.613,respectively. There was no correlation between anti-chromatin antibodies and SLEDAI score （r= 0.124 6,P=0.177 0）. There was no statistical significance in serum anti-chromatin antibodies between SLE patients without nephritis and those with nephritis（P>0.05）. Conclusions Automatic multiplex bead immunoassay for the determination of anti-chromatin antibody plays a role in the diagnosis of connective tissue diseases.

Key words: Anti-chromatin antibody, Automatic multiplex bead immunoassay, Connective tissue disease

中图分类号:

R446.1

王娟, 沈青莹, 王楷文, 赵江峰. 流式点阵免疫发光法检测抗染色质抗体在结缔组织病诊断中的价值[J]. 检验医学, 2019, 34(11): 1021-1025.

WANG Juan, SHEN Qingying, WANG Kaiwen, ZHAO Jiangfeng. Role of anti-chromatin antibody determined by automatic multiplex bead immunoassay in the diagnosis of connective tissue diseases[J]. Laboratory Medicine, 2019, 34(11): 1021-1025.

图/表 5

表1 抗染色质抗体与ANA检测结果的一致性分析

ANA滴度	例数	抗染色质抗体
ANA滴度	例数	阴性例数	阳性例数	阳性率（%）
阴性	20	19	1	5.00
1:40	27	24	3	11.11
1:80	42	32	10	23.81
1:160	103	25	78	75.73
1:320	90	22	68	75.56
1:640	58	3	55	94.83
1:1 280	44	0	44	100.00

图1 SLE组血清抗染色质抗体、抗dsDNA抗体、抗核小体抗体及抗组蛋白抗体的阳性率注：（a）SLE患者中仅单个抗体阳性而其他3种抗体均阴性的百分比;（b）SLE患者4种抗体交叉阳性的示意图

图2 抗染色质抗体、抗dsDNA抗体、抗核小体抗体及抗组蛋白抗体诊断SLE的ROC曲线

图3 抗染色质抗体与SLEDAI评分的相关性分析注：r=0.124 6,P=0.177 0

图4 SLE患者未合并肾炎者与合并肾炎者血清抗染色质抗体水平的比较

参考文献 10

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流式点阵免疫发光法检测抗染色质抗体在结缔组织病诊断中的价值

Role of anti-chromatin antibody determined by automatic multiplex bead immunoassay in the diagnosis of connective tissue diseases

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