Diagnostic Value of Anti-nucleosome Antibody in SLE Patients: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

QIN Li , WU Lijuan , WANG Lanlan , BAI Yangjuan

Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

Keywords：

Anti-nucleosome antibody (AnuA); Diagnosis value; Systemic Lupus Erythematosis (SLE); Systematic review; Meta-analysis

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Objective 　To evaluate the diagnostic value of anti-nucleosome antibody (AnuA) in patients with systemic lupus erythematosus (SLE).
Methods　 We searched MEDLINE, EMbase and The Cochrane Library to identify studies on the diagnostic value of AnuA in patients with SLE. The searching time was from 1990 to 2005. The quality of included studies was evaluated and the data were extracted. The Cochrane Collaboration’s RevMan software was used to analyze heterogeneity, and MetaDisc was used to perform meta-analyses and draw summary receiver operator characteristic curve (SROC).
Results 　Twenty-five studies involving 7 289 patients (2 459 SLE and 5 030 non-SLE patients were diagnosed by gold standard) were included, most of which were poor in quality. The heterogeneity among studies was high (P lt;0.000 01, I2=87.2%). The pooled sensitivity was 64.9%, 95% CI 63.0 to 66.85, and the pooled specificity was 92.6%, 95% CI 91.8% to 93.3%. Area under the SROC was 0.918, SE0.0212. These data suggested that AnuA had a relatively high false negative rate (35.1%) and a relatively low false positive rate (7.4%).
Conclusions 　AnuA has some value in diagnosing SLE and could possibly be used as one of the diagnostic tests for SLE.

Citation： QIN Li,WU Lijuan,WANG Lanlan,BAI Yangjuan. Diagnostic Value of Anti-nucleosome Antibody in SLE Patients: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2007, 07(3): 204-210. doi: Copy

1.	Liu GJ, Wu TX, Kang DY. The statistical process of Meta-analysis, Modern Rehabilitation, 2003, 7(4): 538–539.
2.	Liu GJ, Wu TX. Clinical Implementation of Forest Plots in Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2004, 4(3): 198–201.
3.	Liu GJ, Wu TX. Summary ROC curve-diagnostic test method of Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2003, 3(1): 41–44.
4.	Chen P, Yan L. Study on the relationship between anti-nucleosome antibody and lupus nephritis. Shanghai Journal of Medical Laboratory Sciences, 2004, 19(4): 72–74.
5.	Wu W, Zhen FQ, Li BY, et al. A study on antinucleosome antibody and deoxyribonuclease I activity in SLE patients. Journal of Clinical Dermatology, 2004, 33(6): 83–85.
6.	Zuo XX, Li YS, Wang YP, et al. A Study on Relationship Between Antinucleosome Antibody and Systemic Lupus Erythematosus. Journal of Chinese Physician, 2005, 7(2): 191–192.
7.	Tian QW, Cu KQ, Wang XB, et al. Detection of second filial generation anti-nucleosome antibody in patients with systemic lupus erythematosus. Medical Journal of Qilu, 2003, 18(2): 91–93.
8.	Xu HX, Luo GY, He L, et al. A study for the relationship between antinucleosome autoantibodies, immunoglubine, and complement with activity of SLE. The Journal of Practical Medicine, 2005, 21(9): 931–932.
9.	Su Y, Han L, Li ZG, et al. Significance of anti-nucleosome antibodies in systemic lupus erythematosus. Chinese Journal of Rheumatology, 2003, 7(8): 474–477.
10.	Hu XF, Li XF, Xu K, et al. The value of antinucleosome autoantibodies test in diagnosing systemic SLE. Chinese Journal of Laboratory Medicine, 2005, 28(4): 113–115.
11.	Guo PE, Hui XY, Zhen XY, et al. The value of antinucleosome autoantibodies test in diagnosing systemic SLE. Chinese Journal of Rheumatology, 2003, 7(8): 500–502.
12.	Xu WD, Chen ZH, Liang DH, et al. The value of antinucleosome autoantibodies test in diagnosing systemic SLE. Journal of Zhenjiang Medical College, 2004, 14(6): 539–540.
13.	Zhong Q, Gan H, Chen P, et al. A study for the relationship between antinucleosome autoantibodies and systemic SLE. Chinese Journal of Rheumatology, 2003, 7(2): 111–113.
14.	Han F, Qi WC, Li W, et al. Significance of Anti-Chromatin Antibodies in Diagnosis of Systemic Lupus Erythematosus. Tianjin Medical Journal, 2005, 33(7): 414–415.
15.	Li YS, Zuo XX, Wang YP, et al. Diagnostic Significance of Antinucleosome Antibody for Systemic Lupus Erythematosus. Journal of Clinical Research, 2004, 21(9): 89–90.
16.	Xing JL. Study for the value of two types of authoantibody in the diagnosis of Systemic Lupus Erythematosus. Journal of Sichuan Continuing Education College of Medical Sciences, 2004, 24(1): 112–113.
17.	Yu LL, Lu XM, Zhao TE, et al. Clinical Significance of Antinucleosome antibody in systemic lupus erythematosus. Chinese Journal of Dermatology, 2005, 38(1): 5–7.
18.	Su Y, Jia RL, Li ZG, et al. Significance of combined detection of autoantibodies in systemic lupus erythematosus. Chinese Journal of Rheumatology, 2005, 9(1): 16–18.
19.	刘关键, 吴泰相, 康德英. Meta-分析中的统计学过程. 中国临床康复杂志, 2003, 7(4): 538~539.
20.	刘关键, 吴泰相. Meta-分析的森林图及临床意义. 中国循证医学杂志, 2004, 4(3): 198~201.
21.	刘关键, 吴泰相. 诊断性试验的Meta 分析———SROC 曲线法介绍.中国循证医学杂志, 2003, 3(1): 41~44.
22.	Haddouk SM, Ayed BS, Baklouti, et al. Clinical significance of antinucleosome antibodies in Tunisian systemic lupus erythematosus patients. Clin Rheumatol, 2005, 24: 219–222.
23.	Sallai K, Nagy E, Derfalvy B, et al. Antinucleosome Antibodies and Decreased Deoxyribonuclease Activity in Sera of Patients with Systemic Lupus Erythematosus. Clin Diagn Lab Immunol, 2005, 1: 56–59.
24.	Chabre H, Amoura Z, Piette JC, et al. Presence of nucleosome-restricted antibodies in patients with systemic lupus erythematosus. Arthritis & Rheumatol, 1995, 38(10): 1485–1491.
25.	陈瀑, 严立. 抗核小体抗体与系统性红斑狼疮肾炎相关性研究. 检验医学, 2004, 19(4): 72~74.
26.	吴玮, 曾凡钦, 李伯有, 等. 系统性红斑狼疮患者血清抗核小体抗体和脱氧核糖核酸酶I活性的研究. 临床皮肤科杂志, 2004, 33(6): 83~85.
27.	左晓霞, 李懿莎, 王彦平, 等. 抗核小体抗体与系统性红斑狼疮活动性的相关研究. 中国医师杂志, 2005, 7(2): 191~192.
28.	Sato S, Kodora M, Hasegawa M, et al. Antinucleosome antibody is a major autoantibody in localized scleroderma. Br J Dermatol, 2004, 151: 1182–1188.
29.	Julkunen H, Salonen EM, Walle TK, et al. Anti-nucleosome antibodies in the diagnosis of systemic lupus erythematosus. Scand J Rheumatol, 2005, 34: 122–124.
30.	Villalta D, Tozzoli R, Bizzaro N, et al. The relevance of autoantigen source and cutoff definition in antichromatin (nucleosome) antibody immunoassays. Ann N Y Acad Sci, 2005, 1050: 176–184.
31.	Gonzalez C, Garcia-Berrocal B, Herraez O, et al. Anti-nucleosome, anti-chromatin, anti-dsDNA and antihistone antibody reactivity in systemic lupus erythematosus. Clin Chem Lab Med, 2004, 42(3): 266–272.
32.	Ghirardello A, Doria S, Zampieri, et al. Antinucleosome antibodies in SLE: a two-year follow-up study of 101 patients. J Autoimmun, 2004, 22: 235–240.
33.	Simon JA, Cabiedes J, Ortiz E, et al. Anti-nucleosome antibodies in patients with SLE of recent onset. Rheumatology, 2004, 43: 220-224.
34.	Cervera R, Vinas O, Ramos-Casals M, et al. Anti-chromatin antibodies in SLE: a useful marker for lupus nephropathy. Ann Rheum Dis, 2003, 62–65.
35.	Cairns AP, McMillan SA, Crockard AD, et al. Antinucleosome antibodies in the diagnosis of SLE. Ann Rheum Dis, 2003, 62: 272–273.
36.	Min DJ, Kim SJ, Park SH, et al. Anti-nuclesome ab: significance in lupus patients lacking anti-double-stranded DNA antibody. Clinical and Exp Rheum, 2002, 20: 13–18.
37.	Genevieve S, Daens S, Guillaume MP, et al. Diagnostic specificities and sensitivities of anti dsDNA, anti membrane DNA and anti-nucleosomes autoantibodies. Scand J Clin Lab Invest, 2001, 61(Suppl 235): 61–67.
38.	Zahir A, Sophie K, Henri C, et al. Presence of antinucleosome autoantibodies in a restricted set of connective tissue disease Antinucleosome Antibodies of the IgG3 Subclass are Markers of Renal Pathogenicity in Systemic Lupus Erythematosus. Arthritis Rheum, 2000, 43: 76–84.
39.	Anne B, Stefan B, Gert H, et al. Nucleosme are major T and B cell autoantigens in Systemic Lupus Erythematosus. Arthritis Rheum, 2000, 43: 2307–2315.
40.	Suer W, Da hnrich C, Schlumberger W, et al. Autoantibodies in SLE but not in scleroderma react with protein-stripped nucleosomes. J Autoimmun, 2004, 22: 325–334.
41.	田清武, 初开秋, 王锡波, 等. 第二代抗核小体抗体检测对系统性红斑狼疮的诊断价值. 齐鲁医学杂志, 2003, 18(2): 91~93.
42.	徐红先, 罗贵有, 何林, 等. 抗核小体抗体、免疫球蛋白及补体与系统性红斑狼疮活动性的相关性研究. 实用医学杂志, 2005, 21(9): 931~932.
43.	苏茵, 韩蕾, 栗占国, 等. 抗核小体抗体测定在系统性红斑狼疮诊断中的意义. 中华风湿病学杂志, 2003, 7(8): 474~477.
44.	胡学芳, 李小峰, 许珂, 等. 抗核小体抗体对系统性红斑狼疮的诊断价值. 中华检验医学杂志, 2005, 28(4): 113~115.
45.	郭品娥, 惠小阳, 郑晓玉, 等. 抗核小体抗体对系统性红斑狼疮的诊断价值. 中华风湿病学杂志, 2003, 7(8): 500~502.
46.	徐卫东, 陈昭华, 梁德辉, 等. 抗核小体抗体检测在系统性红斑狼疮诊断中的意义. 江苏大学学报 (医学版), 2004, 14(6): 539~540.
47.	钟清, 甘华, 陈瀑, 等. 抗核小体抗体与系统性红斑狼疮的相关性研究. 中华风湿病学杂志, 2003, 7(2): 111~113.
48.	韩锋, 齐文成, 李巍, 等. 抗核小体抗体在系统性红斑狼疮诊断中的应用. 天津医药, 2005, 33(7): 414~415.
49.	李懿莎, 左晓霞, 王彦平, 等. 抗核小体抗体在系统性红斑狼疮中的诊断意义. 医学临床研究, 2004, 21(9): 89~90.
50.	邢晋玲. 两种自身抗体检测对系统性红斑狼疮诊断价值的探讨. 四川省卫生管理干部学院学报, 2004, 24(1): 112~113.
51.	袁玲玲, 卢宪梅, 赵天恩, 等. 系统性红斑狼疮患者血清抗核小体抗体水平检测及其临床意义. 中华皮肤科杂志, 2005, 38(1): 5~7.
52.	苏茵, 贾汝琳, 栗占国, 等. 自身抗体联合检测在系统性红斑狼疮诊断中的意义. 中华风湿病学杂志, 2005, 9(1): 16~18.

1. Liu GJ, Wu TX, Kang DY. The statistical process of Meta-analysis, Modern Rehabilitation, 2003, 7(4): 538–539.
2. Liu GJ, Wu TX. Clinical Implementation of Forest Plots in Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2004, 4(3): 198–201.
3. Liu GJ, Wu TX. Summary ROC curve-diagnostic test method of Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2003, 3(1): 41–44.
4. Chen P, Yan L. Study on the relationship between anti-nucleosome antibody and lupus nephritis. Shanghai Journal of Medical Laboratory Sciences, 2004, 19(4): 72–74.
5. Wu W, Zhen FQ, Li BY, et al. A study on antinucleosome antibody and deoxyribonuclease I activity in SLE patients. Journal of Clinical Dermatology, 2004, 33(6): 83–85.
6. Zuo XX, Li YS, Wang YP, et al. A Study on Relationship Between Antinucleosome Antibody and Systemic Lupus Erythematosus. Journal of Chinese Physician, 2005, 7(2): 191–192.
7. Tian QW, Cu KQ, Wang XB, et al. Detection of second filial generation anti-nucleosome antibody in patients with systemic lupus erythematosus. Medical Journal of Qilu, 2003, 18(2): 91–93.
8. Xu HX, Luo GY, He L, et al. A study for the relationship between antinucleosome autoantibodies, immunoglubine, and complement with activity of SLE. The Journal of Practical Medicine, 2005, 21(9): 931–932.
9. Su Y, Han L, Li ZG, et al. Significance of anti-nucleosome antibodies in systemic lupus erythematosus. Chinese Journal of Rheumatology, 2003, 7(8): 474–477.
10. Hu XF, Li XF, Xu K, et al. The value of antinucleosome autoantibodies test in diagnosing systemic SLE. Chinese Journal of Laboratory Medicine, 2005, 28(4): 113–115.
11. Guo PE, Hui XY, Zhen XY, et al. The value of antinucleosome autoantibodies test in diagnosing systemic SLE. Chinese Journal of Rheumatology, 2003, 7(8): 500–502.
12. Xu WD, Chen ZH, Liang DH, et al. The value of antinucleosome autoantibodies test in diagnosing systemic SLE. Journal of Zhenjiang Medical College, 2004, 14(6): 539–540.
13. Zhong Q, Gan H, Chen P, et al. A study for the relationship between antinucleosome autoantibodies and systemic SLE. Chinese Journal of Rheumatology, 2003, 7(2): 111–113.
14. Han F, Qi WC, Li W, et al. Significance of Anti-Chromatin Antibodies in Diagnosis of Systemic Lupus Erythematosus. Tianjin Medical Journal, 2005, 33(7): 414–415.
15. Li YS, Zuo XX, Wang YP, et al. Diagnostic Significance of Antinucleosome Antibody for Systemic Lupus Erythematosus. Journal of Clinical Research, 2004, 21(9): 89–90.
16. Xing JL. Study for the value of two types of authoantibody in the diagnosis of Systemic Lupus Erythematosus. Journal of Sichuan Continuing Education College of Medical Sciences, 2004, 24(1): 112–113.
17. Yu LL, Lu XM, Zhao TE, et al. Clinical Significance of Antinucleosome antibody in systemic lupus erythematosus. Chinese Journal of Dermatology, 2005, 38(1): 5–7.
18. Su Y, Jia RL, Li ZG, et al. Significance of combined detection of autoantibodies in systemic lupus erythematosus. Chinese Journal of Rheumatology, 2005, 9(1): 16–18.
19. 刘关键, 吴泰相, 康德英. Meta-分析中的统计学过程. 中国临床康复杂志, 2003, 7(4): 538~539.
20. 刘关键, 吴泰相. Meta-分析的森林图及临床意义. 中国循证医学杂志, 2004, 4(3): 198~201.
21. 刘关键, 吴泰相. 诊断性试验的Meta 分析———SROC 曲线法介绍.中国循证医学杂志, 2003, 3(1): 41~44.
22. Haddouk SM, Ayed BS, Baklouti, et al. Clinical significance of antinucleosome antibodies in Tunisian systemic lupus erythematosus patients. Clin Rheumatol, 2005, 24: 219–222.
23. Sallai K, Nagy E, Derfalvy B, et al. Antinucleosome Antibodies and Decreased Deoxyribonuclease Activity in Sera of Patients with Systemic Lupus Erythematosus. Clin Diagn Lab Immunol, 2005, 1: 56–59.
24. Chabre H, Amoura Z, Piette JC, et al. Presence of nucleosome-restricted antibodies in patients with systemic lupus erythematosus. Arthritis & Rheumatol, 1995, 38(10): 1485–1491.
25. 陈瀑, 严立. 抗核小体抗体与系统性红斑狼疮肾炎相关性研究. 检验医学, 2004, 19(4): 72~74.
26. 吴玮, 曾凡钦, 李伯有, 等. 系统性红斑狼疮患者血清抗核小体抗体和脱氧核糖核酸酶I活性的研究. 临床皮肤科杂志, 2004, 33(6): 83~85.
27. 左晓霞, 李懿莎, 王彦平, 等. 抗核小体抗体与系统性红斑狼疮活动性的相关研究. 中国医师杂志, 2005, 7(2): 191~192.
28. Sato S, Kodora M, Hasegawa M, et al. Antinucleosome antibody is a major autoantibody in localized scleroderma. Br J Dermatol, 2004, 151: 1182–1188.
29. Julkunen H, Salonen EM, Walle TK, et al. Anti-nucleosome antibodies in the diagnosis of systemic lupus erythematosus. Scand J Rheumatol, 2005, 34: 122–124.
30. Villalta D, Tozzoli R, Bizzaro N, et al. The relevance of autoantigen source and cutoff definition in antichromatin (nucleosome) antibody immunoassays. Ann N Y Acad Sci, 2005, 1050: 176–184.
31. Gonzalez C, Garcia-Berrocal B, Herraez O, et al. Anti-nucleosome, anti-chromatin, anti-dsDNA and antihistone antibody reactivity in systemic lupus erythematosus. Clin Chem Lab Med, 2004, 42(3): 266–272.
32. Ghirardello A, Doria S, Zampieri, et al. Antinucleosome antibodies in SLE: a two-year follow-up study of 101 patients. J Autoimmun, 2004, 22: 235–240.
33. Simon JA, Cabiedes J, Ortiz E, et al. Anti-nucleosome antibodies in patients with SLE of recent onset. Rheumatology, 2004, 43: 220-224.
34. Cervera R, Vinas O, Ramos-Casals M, et al. Anti-chromatin antibodies in SLE: a useful marker for lupus nephropathy. Ann Rheum Dis, 2003, 62–65.
35. Cairns AP, McMillan SA, Crockard AD, et al. Antinucleosome antibodies in the diagnosis of SLE. Ann Rheum Dis, 2003, 62: 272–273.
36. Min DJ, Kim SJ, Park SH, et al. Anti-nuclesome ab: significance in lupus patients lacking anti-double-stranded DNA antibody. Clinical and Exp Rheum, 2002, 20: 13–18.
37. Genevieve S, Daens S, Guillaume MP, et al. Diagnostic specificities and sensitivities of anti dsDNA, anti membrane DNA and anti-nucleosomes autoantibodies. Scand J Clin Lab Invest, 2001, 61(Suppl 235): 61–67.
38. Zahir A, Sophie K, Henri C, et al. Presence of antinucleosome autoantibodies in a restricted set of connective tissue disease Antinucleosome Antibodies of the IgG3 Subclass are Markers of Renal Pathogenicity in Systemic Lupus Erythematosus. Arthritis Rheum, 2000, 43: 76–84.
39. Anne B, Stefan B, Gert H, et al. Nucleosme are major T and B cell autoantigens in Systemic Lupus Erythematosus. Arthritis Rheum, 2000, 43: 2307–2315.
40. Suer W, Da hnrich C, Schlumberger W, et al. Autoantibodies in SLE but not in scleroderma react with protein-stripped nucleosomes. J Autoimmun, 2004, 22: 325–334.
41. 田清武, 初开秋, 王锡波, 等. 第二代抗核小体抗体检测对系统性红斑狼疮的诊断价值. 齐鲁医学杂志, 2003, 18(2): 91~93.
42. 徐红先, 罗贵有, 何林, 等. 抗核小体抗体、免疫球蛋白及补体与系统性红斑狼疮活动性的相关性研究. 实用医学杂志, 2005, 21(9): 931~932.
43. 苏茵, 韩蕾, 栗占国, 等. 抗核小体抗体测定在系统性红斑狼疮诊断中的意义. 中华风湿病学杂志, 2003, 7(8): 474~477.
44. 胡学芳, 李小峰, 许珂, 等. 抗核小体抗体对系统性红斑狼疮的诊断价值. 中华检验医学杂志, 2005, 28(4): 113~115.
45. 郭品娥, 惠小阳, 郑晓玉, 等. 抗核小体抗体对系统性红斑狼疮的诊断价值. 中华风湿病学杂志, 2003, 7(8): 500~502.
46. 徐卫东, 陈昭华, 梁德辉, 等. 抗核小体抗体检测在系统性红斑狼疮诊断中的意义. 江苏大学学报 (医学版), 2004, 14(6): 539~540.
47. 钟清, 甘华, 陈瀑, 等. 抗核小体抗体与系统性红斑狼疮的相关性研究. 中华风湿病学杂志, 2003, 7(2): 111~113.
48. 韩锋, 齐文成, 李巍, 等. 抗核小体抗体在系统性红斑狼疮诊断中的应用. 天津医药, 2005, 33(7): 414~415.
49. 李懿莎, 左晓霞, 王彦平, 等. 抗核小体抗体在系统性红斑狼疮中的诊断意义. 医学临床研究, 2004, 21(9): 89~90.
50. 邢晋玲. 两种自身抗体检测对系统性红斑狼疮诊断价值的探讨. 四川省卫生管理干部学院学报, 2004, 24(1): 112~113.
51. 袁玲玲, 卢宪梅, 赵天恩, 等. 系统性红斑狼疮患者血清抗核小体抗体水平检测及其临床意义. 中华皮肤科杂志, 2005, 38(1): 5~7.
52. 苏茵, 贾汝琳, 栗占国, 等. 自身抗体联合检测在系统性红斑狼疮诊断中的意义. 中华风湿病学杂志, 2005, 9(1): 16~18.

Chinese Journal of Evidence-Based Medicine

Diagnostic Value of Anti-nucleosome Antibody in SLE Patients: A Systematic Review

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