Lu Ruijing, Yu Rui, Huang Rong, Xue Chiyuan, Song Ning, Zhao Jiulang, Zeng Xiaofeng, Hu Chaojun
Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
Department of Laboratory Medicine, Shenzhen Baoan Women's and Children's Hospital, Shenzhen, China.
Front Immunol. 2025 Apr 10;16:1529484. doi: 10.3389/fimmu.2025.1529484. eCollection 2025.
Anti-double-stranded DNA (anti-dsDNA) antibodies at abnormal titer are of considerable diagnostic value for systemic lupus erythematosus (SLE). Current assays detecting anti-dsDNA antibodies show divergent properties, emphasizing the importance of selecting suitable assays. This study aims to investigate the diagnostic performance of indirect immunofluorescence (IIF), digital liquid chip method (DLCM), chemiluminescence immunoassay (CLIA), and their combinations for detecting anti-dsDNA antibodies in SLE.
We conducted a retrospective, single-center study from 2022 to 2023 which included 3429 samples: 1773 from patients with SLE and 1656 from controls with rheumatoid arthritis (RA) and Sjögren's syndrome (SS). Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for anti-dsDNA detection by IIF, DLCM, and CLIA were calculated. Cohen's kappa coefficient was used to evaluate inter-method agreement. The correlations between anti-dsDNA concentration and SLEDAI-2k scores/renal involvement were assessed.
Among individual assays, IIF demonstrated the highest specificity (98.31%) and PPV (96.10%) but lower sensitivity (38.92%) compared to CLIA (41.57%) and DLCM (43.65%) (p < 0.05). Combining two assays significantly improved sensitivity while maintaining specificity>95%. The combination of IIF and DLCM achieved a sensitivity of 52.2% and an AUC of 0.76. Substantial agreement was observed between DLCM and CLIA (κ = 0.78), whereas agreement between IIF and the other assays was moderate (κ = 0.65-0.66). In a longitudinal analysis of 88 SLE patients, CLIA and DLCM detected antibody fluctuations more reliably than IIF. Anti-dsDNA levels by DLCM or CLIA positively correlated with SLEDAI-2K scores (R=0.42 and 0.29, p<0.05). Both IIF and CLIA methods showed significant differences between the SLE patients with and without renal involvement (p < 0.05). The combination of two assays provided higher sensitivity than single assays (p<0.001) in renal involvement subgroups.
Our findings demonstrate that DLCM performs comparably to CLIA, supporting its clinical potential. Moreover, combining assays significantly enhances diagnostic sensitivity, particularly in subgroups with renal involvement.
异常滴度的抗双链DNA（anti-dsDNA）抗体对系统性红斑狼疮（SLE）具有重要的诊断价值。目前检测抗dsDNA抗体的方法具有不同的特性，这凸显了选择合适检测方法的重要性。本研究旨在探讨间接免疫荧光法（IIF）、数字液相芯片法（DLCM）、化学发光免疫分析法（CLIA）及其联合检测在SLE患者中检测抗dsDNA抗体的诊断性能。
我们进行了一项回顾性单中心研究，时间跨度为2022年至2023年，纳入3429份样本：1773份来自SLE患者，1656份来自类风湿关节炎（RA）和干燥综合征（SS）对照组。计算了IIF、DLCM和CLIA检测抗dsDNA的敏感性、特异性、准确性、阳性预测值（PPV）和阴性预测值（NPV）。采用Cohen's kappa系数评估方法间的一致性。评估抗dsDNA浓度与SLEDAI-2k评分/肾脏受累之间的相关性。
在各单项检测方法中，IIF显示出最高的特异性（98.31%）和PPV（96.10%），但与CLIA（41.57%）和DLCM（43.65%）相比，敏感性较低（38.92%）（p<0.05）。两种检测方法联合使用可显著提高敏感性，同时保持特异性>95%。IIF和DLCM联合使用的敏感性为52.2%，AUC为0.76。DLCM和CLIA之间观察到高度一致性（κ=0.78），而IIF与其他检测方法之间的一致性为中等（κ=0.65-0.66）。在对88例SLE患者的纵向分析中，CLIA和DLCM比IIF更可靠地检测到抗体波动。DLCM或CLIA检测的抗dsDNA水平与SLEDAI-2K评分呈正相关（R=0.42和0.29，p<0.05）。IIF和CLIA方法在有和无肾脏受累的SLE患者之间均显示出显著差异（p<0.05）。在肾脏受累亚组中，两种检测方法联合使用比单一检测方法具有更高的敏感性（p<0.001）。
我们的研究结果表明，DLCM的性能与CLIA相当，支持其临床应用潜力。此外，联合检测可显著提高诊断敏感性，尤其是在肾脏受累亚组中。
