ICERA Consulting Ltd, Swindon, UK.
Thermo Fisher Scientific, Phadia AB, Uppsala, Sweden.
J Appl Lab Med. 2022 Jan 5;7(1):221-239. doi: 10.1093/jalm/jfab146.
Autoantibody specificity in autoimmune diseases is variable due to each patient's individual spectrum of autoantibodies and the inherent differences between detection methods and tests. Since false-positive results have downstream consequences, we conducted a comprehensive assessment of anti-double stranded DNA (anti-dsDNA) specificity from published studies of systemic lupus erythematosus (SLE).
A systematic review (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Database of Abstracts of Reviews of Effects) identified cross-sectional or case-control studies published January 2004 to August 2019, reporting anti-dsDNA test accuracy data in SLE. Study quality was assessed using Quality Assessment Tool for Diagnostic Accuracy Studies, version 2. A meta-analysis was conducted to estimate specificity by test method or named test where feasible.
Thirty studies were included covering 43 different tests. The Crithidia luciliae indirect immunofluorescence test (CLIFT) and fluorescence enzyme immunoassay methods are likely to be ≥ 90% specific (Euroimmun 97.8% (95% CI 96.2%-98.7%) 4 studies; EliA 94.7% (95% CI 91.7%-96.7%), 6 studies; CLIFT 98.7% (95% CI 96.7%-99.5%), 8 studies/7 tests]. For other test methods, specificity was not fully demonstrated to be ≥ 90% and/or the control group included healthy patients possibly overestimating specificity. More studies are required for NOVA Lite [96.0% (95% CI 87.2%-98.9%), 5 studies], chemiluminescence immunoassays [92.3% (95% CI 83.6%-96.6%), 6 studies/4 tests], multiplex immunoassays [89.3% (95% CI 86.1%-91.8%), 4 studies/2 tests], and Farr fluorescent immunoassays (no estimate, 2 studies). Specificity data reported for Farr radioimmunoassays [93.8% (95% CI 85.4-97.5%), 11 studies, 9 tests] and enzyme-linked immunosorbent assays [93.4% (95% CI 89.9%-95.7%), 15 studies/16 tests] lacked consistency.
Anti-dsDNA testing shows considerable variation in test specificity, with potential impact on the management of SLE patients. This review may help laboratory specialists and clinicians choose and interpret the appropriate anti-dsDNA test for their setting.
由于每个患者自身的抗体谱以及检测方法和检测试验之间的固有差异，自身免疫性疾病中的自身抗体特异性各不相同。由于假阳性结果会带来后续影响，我们对系统性红斑狼疮（SLE）的已发表研究进行了全面评估，以确定抗双链 DNA（抗 dsDNA）的特异性。
通过系统检索（MEDLINE、Embase、Cochrane 对照试验中心注册库和效应评价数据库），我们确定了 2004 年 1 月至 2019 年 8 月期间发表的横断面或病例对照研究，报告了 SLE 中抗 dsDNA 检测准确性数据。使用诊断准确性研究的质量评估工具（第二版）评估研究质量。如果可行，我们将进行荟萃分析以估计检测方法或特定检测的特异性。
共纳入 30 项研究，涵盖 43 种不同的检测方法。克鲁氏锥虫间接免疫荧光试验（CLIFT）和荧光酶免疫分析方法的特异性可能≥90%（Euroimmun 97.8%（95% CI 96.2%-98.7%），4 项研究；EliA 94.7%（95% CI 91.7%-96.7%），6 项研究；CLIFT 98.7%（95% CI 96.7%-99.5%），8 项研究/7 种检测）。对于其他检测方法，特异性未被充分证明≥90%，且/或对照组纳入了可能高估特异性的健康患者。对于 NOVA Lite [96.0%（95% CI 87.2%-98.9%），5 项研究]、化学发光免疫分析[92.3%（95% CI 83.6%-96.6%），6 项研究/4 种检测]、多重免疫分析[89.3%（95% CI 86.1%-91.8%），4 项研究/2 种检测]和 Farr 荧光免疫分析（无估计值，2 项研究），需要开展更多研究。Farr 放射免疫分析（93.8%（95% CI 85.4-97.5%），11 项研究，9 种检测）和酶联免疫吸附测定（93.4%（95% CI 89.9%-95.7%），15 项研究/16 种检测）的特异性数据缺乏一致性。
抗 dsDNA 检测的特异性差异较大，可能对 SLE 患者的管理产生影响。本综述可能有助于实验室专家和临床医生为其所在环境选择和解释适当的抗 dsDNA 检测。
