Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University
Rheumatology (Oxford). 2015 Mar;54(3):449-57. doi: 10.1093/rheumatology/keu326. Epub 2014 Sep 5.
The aim of this study was to determine whether anti-nucleosome antibodies function as activity-specific biomarkers in SLE.
Fifty-one patients were recruited and followed prospectively with periodic clinical and biochemical assessments over a 14-month period. Disease activity was determined by the SLEDAI-2K. Anti-nucleosome antibody levels were measured by an ELISA and its utility as an activity-specific biomarker as compared with that of anti-dsDNA antibodies and C3 was assessed both at baseline and in longitudinal analysis.
Anti-nucleosome antibodies were significantly elevated in SLE patients vs controls and showed a moderate positive correlation with disease activity. The utility of anti-nucleosome antibodies in identifying patients with active disease in a cross-sectional analysis was comparable to that of anti-dsDNA antibodies and C3. Analysis of variance demonstrated that the level of anti-nucleosome antibodies and C3 varied significantly with changes in disease activity over time. Changes in clinical state were not mirrored by changes in anti-dsDNA antibodies. In time-dependent analysis, anti-nucleosome antibodies showed a better fit over time than anti-dsDNA antibodies and C3. In pairwise comparisons, C3 and anti-nucleosome antibodies outperformed other models, including the conventional pairing of C3 and anti-dsDNA antibodies, however, no biomarker alone or as a group accurately predicted impending remissions or exacerbations.
Anti-nucleosome antibodies demonstrate greater fidelity as a biomarker for changes in SLE disease activity than traditional biomarkers, supporting the routine monitoring of this antibody in clinical practice.
本研究旨在确定抗核小体抗体是否可作为 SLE 中的一种特异性活动生物标志物。
招募了 51 名患者,并进行了前瞻性随访,在 14 个月的时间内定期进行临床和生化评估。采用 SLEDAI-2K 评估疾病活动度。通过 ELISA 测量抗核小体抗体水平,并在基线和纵向分析中评估其作为特异性活动生物标志物的效用,与抗 dsDNA 抗体和 C3 进行比较。
与对照组相比,SLE 患者的抗核小体抗体明显升高,并与疾病活动度呈中度正相关。在横断面分析中,抗核小体抗体识别活动期疾病患者的效用与抗 dsDNA 抗体和 C3 相当。方差分析表明,抗核小体抗体和 C3 的水平随时间的推移而发生显著变化,与疾病活动度的变化一致。抗 dsDNA 抗体的变化并未反映临床状态的变化。在时间依赖性分析中,抗核小体抗体的拟合度优于抗 dsDNA 抗体和 C3。在两两比较中,C3 和抗核小体抗体优于其他模型,包括 C3 和抗 dsDNA 抗体的传统配对,但没有任何一种生物标志物单独或作为一组能够准确预测即将发生的缓解或恶化。
与传统生物标志物相比,抗核小体抗体作为 SLE 疾病活动变化的生物标志物具有更高的准确性,支持在临床实践中常规监测该抗体。