[抗核抗体多重免疫分析在系统性红斑狼疮中的临床价值。]

[Clinical value of multiplex immune assay of antinuclear antibodies in systemic lupus erythematosus.].

作者信息

Aleksandrova E N, Verizhnikova Zh G, Novikov A A, Panafidina T A, Popkova T V, Lukina G V

机构信息

A.S. Loginov Moscow Clinical Research and Practical Center, Moscow Healthcare Department, 111123, Moscow, Russia.

V.A. Nasonova Research Institute of Rheumatology, 115522, Moscow, Russia.

出版信息

Klin Lab Diagn. 2018;63(7):434-438. doi: 10.18821/0869-2084-2018-63-7-434-438.

DOI:10.18821/0869-2084-2018-63-7-434-438

PMID:30720960

Abstract

A promising trend in the diagnosis of systemic autoimmune diseases is the multiplex immune assay (MIA) of autoantibodies and other laboratory biomarkers using microchips. The aim of the work was to study the diagnostic and prognostic significance of MIA antinuclear antibody (ANA) profiles in systemic lupus erythematosus (SLE). 94 patients with SLE, 70 patients with other rheumatic diseases and 30 healthy donors were examined. ANA (antibodies to doublestranded - dsDNA, Sm, SS-A/Ro, SS-B/La antigens, nucleosomes, ribosomal protein P-RibP and ribonucleoprotein - RNP-70) were determined in the serum by MIA using the xMAP technology. In MIA, antibodies to dsDNA, Sm and RibP have a high diagnostic specificity (Sp) (95.0-99.0%) and a likelihood ratio of positive results (LR+) (9.67-15.0), i.e. are the most "useful" diagnostic tests, and antibodies to RNP-70, SS-A/Ro and nucleosomes are classified as "useful" tests for the diagnosis of SLE (Sp: 84.0-95.0%, LR+> 2.0). Determination of profiles from 3 or more antigen-specific ANA by MIA increases the Sp method to 98.0-100%, and the LR+ - to the maximum values. Profiles from 7 subpopulations of ANA (antibodies to dsDNA, Sm, RibP, SS-A/Ro,SS-B/La, nucleosomes and RNP-70, 57.9%, 71.9%, 82.5%, 61.4 %, 84.2%, 50.9%, 84.2%) were found in the chronic variant of SLE. In the acute course of the disease, 4 subpopulations of ANA are simultaneously detected (antibodies to dsDNA, Sm, SS-A/Ro and nucleosomes, 77.3%, 45.5%, 40.9% and 72.7%); in subacute course there are 2 subpopulations of ANA (antibodies to dsDNA and nucleosomes, 53.3% and 46.7%). The activity index of SLEDAI-2K positively correlates with the concentration of antibodies to dsDNA (r = 0.55, p < 0.05), nucleosomes (r = 0.65, p < 0.05), RibP (r = 0.32; p < 0.05) and Sm (r = 0.36, p < 0.05) in the blood. There was no reliable relationship between the production of varieties of ANA and the index of organ damage. Mucocutaneous disorders, lupus-nephritis and neurolupus were most often associated with the detection of antibodies to dsDNA (53.2-64.0%), nucleosomes (55.3-66.0%), SS-A/Ro (38.0-40.4%) and Sm (27.8-36.2%). MIA of ANA profiles is an important tool for implementing a personalized approach to diagnosis, evaluation of activity, course and clinical and immunologic subtypes of SLE.

摘要

自身抗体和其他实验室生物标志物的微芯片多重免疫分析（MIA）是系统性自身免疫性疾病诊断中一个很有前景的趋势。本研究旨在探讨MIA抗核抗体（ANA）谱在系统性红斑狼疮（SLE）中的诊断和预后意义。对94例SLE患者、70例其他风湿性疾病患者和30名健康供者进行了检测。采用xMAP技术通过MIA测定血清中的ANA（抗双链 - dsDNA、Sm、SS - A/Ro、SS - B/La抗原、核小体、核糖体蛋白P - RibP和核糖核蛋白 - RNP - 70抗体）。在MIA中，抗dsDNA、Sm和RibP抗体具有较高的诊断特异性（Sp）（95.0 - 99.0%）和阳性结果似然比（LR +）（9.67 - 15.0），即它们是最“有用”的诊断检测项目，而抗RNP - 70、SS - A/Ro和核小体抗体被归类为SLE诊断的“有用”检测项目（Sp：84.0 - 95.0%，LR +> 2.0）。通过MIA检测3种或更多抗原特异性ANA的谱可将该方法的Sp提高到98.0 - 100%，LR +提高到最大值。在SLE的慢性期发现了7种ANA亚群的谱（抗dsDNA、Sm、RibP、SS - A/Ro、SS - B/La、核小体和RNP - 70抗体，分别为57.9%、71.9%、82.5%、61.4%、84.2%、50.9%、84.2%）。在疾病的急性期，同时检测到4种ANA亚群（抗dsDNA、Sm、SS - A/Ro和核小体抗体，分别为77.3%、45.5%、40.9%和72.7%）；在亚急性期有2种ANA亚群（抗dsDNA和核小体抗体，分别为53.3%和46.7%）。SLEDAI - 2K活动指数与血液中抗dsDNA（r = 0.55，p < 0.05）、核小体（r = 0.65，p < .05）、RibP（r = 0.32；p < 0.05）和Sm（r = 0.36，p < 0.05）抗体浓度呈正相关。ANA各亚型的产生与器官损伤指数之间没有可靠的关系。皮肤黏膜病变、狼疮性肾炎和神经精神性狼疮最常与抗dsDNA（53.2 - 64.0%）、核小体（55.3 - 66.0%）、SS - A/Ro（38.0 - 40.4%）和Sm（27.8 - 36.2%）抗体的检测相关。ANA谱的MIA是实施个性化诊断方法、评估SLE活动度、病程以及临床和免疫亚型的重要工具。