Diagnostic Value of Serum anti-C1q Antibodies for Lupus Nephritis in Chinese Population: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 WANGZi-xia ¹ , WANGQi-xian ² ,  ZENGHong-bing ¹ , SHIJing ³

1. Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;
2. Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China;
3. Department of Respiration and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;

Corresponding author：

ZENGHong-bing, Email: zeng_hong_bing@163.com

Keywords：

Systemic lupus erythematosus; Lupus nephritis; Anti-C1q; Meta-analysis; Diagnostic test

DOI：

10.7507/1672-2531.20150154

Video：

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Objective To systematically review the diagnostic value of anti-C1q antibodies for lupus nephritis (LN) in Chinese population. Methods We electronically searched databases including PubMed, EMbase, CNKI, The Cochrane Library, VIP and WanFang Data for diagnostic accuracy studies of anti-C1q antibodies for LN in Chinese population from inception to 1st March, 2015. Two reviewers independently screened literature, extracted data and assessed the risk bias of included studies by QUADAS tool. Then, meta-analysis was performed by Meta-DiSc 1.4 software and Stata 11.0 software. Results A total of 11 studies involving 1 084 systemic lupus erythematosus (SLE) patients were included. Among them, 474 patients were LN. The results of meta-analysis showed that:the pooled sensitivity, specificity, diagnostic odds ratio, positive likelihood ratio, and negative likelihood ratio of anti-C1q in the diagnosis of LN were 0.67 (95%CI 0.63 to 0.71), 0.69 (95%CI 0.65 to 0.74), 5.09 (95%CI 3.29 to 7.85), 2.18 (95%CI 1.75 to 2.72), and 0.48 (95%CI 0.39 to 0.60), respectively. The area under the curve (AUC) of SROC was 0.749 6 and the Q index value was 0.693 1. The average missed diagnosis rate was 33.0% and the misdiagnosis rate was 31.0%. Conclusion Current evidence indicates that anti-C1q antibodies may have some value in the diagnosis of LN. Because of the high missed diagnosis rate and the misdiagnosis rate, it could not be used to diagnose LN alone, and it only could be used as an adjuvant diagnostic indicator for LN. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.

Citation： WANGZi-xia, WANGQi-xian, ZENGHong-bing, SHIJing. Diagnostic Value of Serum anti-C1q Antibodies for Lupus Nephritis in Chinese Population: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2015, 15(8): 914-921. doi: 10.7507/1672-2531.20150154 Copy

1.	Danila MI, Pons-Estel GJ, Zhang J, et al. Renal damage is the most important predictor of mortality within the damage index:data from LUMINA LXIV, a multiethnic US cohort. Rheumatology (Oxford), 2009, 48(5):542-545.
2.	Lu L, Kaliyaperumal A, Boumpas DT, et al. Major peptide autoepitopes for nucleosome-specific T cells of human lupus. J Clin Invest, 1999, 104(3):345-355.
3.	Uwatoko S, Aotsuka S, Okawa M, et al. Characterization of C1q-binding IgG complexes in systemic lupus erythematosus. Clin Immunol Immunopathol, 1984, 30(1):104-116.
4.	Potlukova E, Kralikova P. Complement component c1q and anti-c1q antibodies in theory and in clinical practice. Scand J Immunol, 2008, 67(5):423-430.
5.	Trouw LA, Daha MR. Role of anti-C1q autoantibodies in the pathogenesis of lupus nephritis. Expert Opin Biol Ther, 2005, 5(2):243-251.
6.	Potlukova E, Jiskra J, Limanova Z, et al. Autoantibodies against complement C1q correlate with the thyroid function in patients with autoimmune thyroid disease. Clin Exp Immunol, 2008, 153(1):96-101.
7.	Saadoun D, Sadallah S, Trendelenburg M, et al. Anti-C1q antibodies in hepatitis C virus infection. Clin Exp Immunol, 2006, 145(2):308-312.
8.	Meyer OC, Nicaise-Roland P, Cadoudal N, et al. Anti-C1q antibodies antedate patent active glomerulonephritis in patients with systemic lupus erythematosus. Arthritis Res Ther, 2009, 11(3):87.
9.	Moura CG, Mangueira CL, Cruz LA, et al. Negative anti-C1q antibody titers may influence therapeutic decisions and reduce the number of renal biopsies in systemic lupus erythematosus. Nephron Clin Pract, 2011, 118(4):355-360.
10.	Marto N, Bertolaccini ML, Calabuig E, et al. Anti-C1q antibodies in nephritis:correlation between titres and renal disease activity and positive predictive value in systemic lupus erythematosus. Ann Rheum Dis, 2005, 64(3):444-448.
11.	Moroni G, Radice A, Giammarresi G, et al. Are laboratory tests useful for monitoring the activity of lupus nephritis? A 6-year prospective study in a cohort of 228 patients with lupus nephritis. Ann Rheum Dis, 2009, 68(2):234-237.
12.	Julkunen H, Ekblom-Kullberg S, Miettinen A. Nonrenal and renal activity of systemic lupus erythematosus:a comparison of two anti-C1q and five anti-dsDNA assays and complement C3 and C4. Rheumatol Int, 2012, 32(8):2445-2451.
13.	Akhter E, Burlingame RW, Seaman AL, et al. Anti-C1q antibodies have higher correlation with flares of lupus nephritis than other serum markers. Lupus, 2011, 20(12):1267-1274.
14.	Katsumata Y, Miyake K, Kawaguchi Y, et al. Anti-C1q antibodies are associated with systemic lupus erythematosus global activity but not specifically with nephritis:a controlled study of 126 consecutive patients. Arthritis Rheum, 2011, 63(8):2436-2444.
15.	Yin Y, Wu X, Shan G, et al. Diagnostic value of serum anti-C1q antibodies in patients with lupus nephritis:a meta-analysis. Lupus, 2012, 21(10):1088-1097.
16.	Eggleton P, Ukoumunne OC, Cottrell I, et al. Autoantibodies against C1q as a Diagnostic Measure of Lupus Nephritis:Systematic Review and Meta-analysis. J Clin Cell Immunol, 2014, 5(2):210.
17.	Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum, 1997, 40(9):1725.
18.	Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum, 1982, 25(11):1271-1277.
19.	Whiting P, Rutjes AW, Reitsma JB, et al. The development of QUADAS:a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol, 2003, 3:25.
20.	Deville WL, Buntinx F, Bouter LM, et al. Conducting systematic reviews of diagnostic studies:didactic guidelines. BMC Med Res Methodol, 2002, 2:9.
21.	Egger B, Schmid SW, Schafer M, et al.[2-year evaluation of a cooperation model between a surgical university clinic and a general hospital]. Chirurg, 2001, 72(1):30-36.
22.	郭珲, 罗静, 李荣山, 等. 抗核小体抗体与抗C1q抗体在狼疮肾炎血清的表达及其临床意义. 中华风湿病学杂志, 2005, 9(8):479-481.
23.	王琴, 杨铁生, 樊春红. 血清C1q抗体水平与系统性红斑狼疮活动性和狼疮肾炎的关系. 临床内科杂志, 2007, 24(4):238-240.
24.	罗宇鸿, 付俊, 张洪海. 联合检测血清中C1q抗体、IL-18对系统性红斑狼疮的诊断价值. 实用临床医学, 2009, 10(1):4-6, 9.
25.	王丽, 王琳. 狼疮肾炎患者血清自身抗体检测及意义. 中国基层医药, 2010, 17(21):2917-2918.
26.	冯江超, 青玉凤, 周京国. 血清抗C1q抗体在系统性红斑狼疮活动性判断及狼疮肾炎诊断中的价值. 免疫学杂志, 2010, (3):228-231.
27.	李娜, 李宝全, 巩路. 抗C1q抗体在系统性红斑狼疮及狼疮肾炎诊断中的作用. 天津医学大学学报, 2011, 17(4):546-548.
28.	崔婵娟, 柏明见, 冯珍如, 等. 血清抗C1q抗体在评价系统性红斑活动性及狼疮性肾炎病理分型中的临床意义. 中国全科医学, 2014, 17(17):1989-1993.
29.	Tan Y, Zhou W, Yu F, et al. Detection of anti-C1q antibodies and anti-C1q globular head domain antibodies in sera from Chinese patients with lupus nephritis. Mol Immunol, 2009, 46(11-12):2178-2182.
30.	Fang QY, Yu F, Tan Y, et al. Anti-C1q antibodies and IgG subclass distribution in sera from Chinese patients with lupus nephritis. Nephrol Dial Transplant, 2009, 24(1):172-178.
31.	Wu FQ, Zhao Q, Cui XD, et al. C1q and anti-C1q antibody levels are correlated with disease severity in Chinese pediatric systemic lupus erythematosus. Rheumatol Int, 2011, 31(4):501-505.
32.	Zhang CQ, Ren L, Gao F, et al. Anti-C1q antibodies are associated with systemic lupus erythematosus disease activity and lupus nephritis in northeast of China. Clin Rheumatol, 2011, 30(7):967-973.
33.	Botto M, Dell'Agnola C, Bygrave AE, et al. Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat Genet, 1998, 19(1):56-59.
34.	Tsacheva I, Radanova M, Todorova N, et al. Detection of autoantibodies against the globular domain of human C1q in the sera of systemic lupus erythematosus patients. Mol Immunol, 2007, 44(8):2147-2151.
35.	Coremans IE, Daha MR, van der Voort EA, et al. Antibodies against C1q in anti-glomerular basement membrane nephritis. Clin Exp Immunol, 1992, 87(2):256-260.
36.	Mahler M, van Schaarenburg RA, Trouw LA. Anti-C1q autoantibodies, novel tests, and clinical consequences. Front Immunol, 2013, 5(4):117.
37.	Moura CG, Lima I, Barbosa L, et al. Anti-C1q antibodies:association with nephritis and disease activity in systemic lupus erythematosus. J Clin Lab Anal, 2009, 23(1):19-23.
38.	Moroni G, Quaglini S, Radice A, et al. The value of a panel of autoantibodies for predicting the activity of lupus nephritis at time of renal biopsy. J Immunol Res, 2015, 2015:106904.
39.	Oelzner P, Deliyska B, Funfstuck R, et al. Anti-C1q antibodies and antiendothelial cell antibodies in systemic lupus erythematosus-relationship with disease activity and renal involvement. Clin Rheumatol, 2003, 22(4-5):271-278.
40.	Grootscholten C, Dieker JW, McGrath FD, et al. A prospective study of anti-chromatin and anti-C1q autoantibodies in patients with proliferative lupus nephritis treated with cyclophosphamide pulses or azathioprine/methylprednisolone. Ann Rheum Dis, 2007, 66(5):693-696.
41.	Yang XW, Tan Y, Yu F, et al. Combination of anti-C1q and anti-dsDNA antibodies is associated with higher renal disease activity and predicts renal prognosis of patients with lupus nephritis. Nephrol Dial Transplant, 2012, 27(9):3552-3559.

1. Danila MI, Pons-Estel GJ, Zhang J, et al. Renal damage is the most important predictor of mortality within the damage index:data from LUMINA LXIV, a multiethnic US cohort. Rheumatology (Oxford), 2009, 48(5):542-545.
2. Lu L, Kaliyaperumal A, Boumpas DT, et al. Major peptide autoepitopes for nucleosome-specific T cells of human lupus. J Clin Invest, 1999, 104(3):345-355.
3. Uwatoko S, Aotsuka S, Okawa M, et al. Characterization of C1q-binding IgG complexes in systemic lupus erythematosus. Clin Immunol Immunopathol, 1984, 30(1):104-116.
4. Potlukova E, Kralikova P. Complement component c1q and anti-c1q antibodies in theory and in clinical practice. Scand J Immunol, 2008, 67(5):423-430.
5. Trouw LA, Daha MR. Role of anti-C1q autoantibodies in the pathogenesis of lupus nephritis. Expert Opin Biol Ther, 2005, 5(2):243-251.
6. Potlukova E, Jiskra J, Limanova Z, et al. Autoantibodies against complement C1q correlate with the thyroid function in patients with autoimmune thyroid disease. Clin Exp Immunol, 2008, 153(1):96-101.
7. Saadoun D, Sadallah S, Trendelenburg M, et al. Anti-C1q antibodies in hepatitis C virus infection. Clin Exp Immunol, 2006, 145(2):308-312.
8. Meyer OC, Nicaise-Roland P, Cadoudal N, et al. Anti-C1q antibodies antedate patent active glomerulonephritis in patients with systemic lupus erythematosus. Arthritis Res Ther, 2009, 11(3):87.
9. Moura CG, Mangueira CL, Cruz LA, et al. Negative anti-C1q antibody titers may influence therapeutic decisions and reduce the number of renal biopsies in systemic lupus erythematosus. Nephron Clin Pract, 2011, 118(4):355-360.
10. Marto N, Bertolaccini ML, Calabuig E, et al. Anti-C1q antibodies in nephritis:correlation between titres and renal disease activity and positive predictive value in systemic lupus erythematosus. Ann Rheum Dis, 2005, 64(3):444-448.
11. Moroni G, Radice A, Giammarresi G, et al. Are laboratory tests useful for monitoring the activity of lupus nephritis? A 6-year prospective study in a cohort of 228 patients with lupus nephritis. Ann Rheum Dis, 2009, 68(2):234-237.
12. Julkunen H, Ekblom-Kullberg S, Miettinen A. Nonrenal and renal activity of systemic lupus erythematosus:a comparison of two anti-C1q and five anti-dsDNA assays and complement C3 and C4. Rheumatol Int, 2012, 32(8):2445-2451.
13. Akhter E, Burlingame RW, Seaman AL, et al. Anti-C1q antibodies have higher correlation with flares of lupus nephritis than other serum markers. Lupus, 2011, 20(12):1267-1274.
14. Katsumata Y, Miyake K, Kawaguchi Y, et al. Anti-C1q antibodies are associated with systemic lupus erythematosus global activity but not specifically with nephritis:a controlled study of 126 consecutive patients. Arthritis Rheum, 2011, 63(8):2436-2444.
15. Yin Y, Wu X, Shan G, et al. Diagnostic value of serum anti-C1q antibodies in patients with lupus nephritis:a meta-analysis. Lupus, 2012, 21(10):1088-1097.
16. Eggleton P, Ukoumunne OC, Cottrell I, et al. Autoantibodies against C1q as a Diagnostic Measure of Lupus Nephritis:Systematic Review and Meta-analysis. J Clin Cell Immunol, 2014, 5(2):210.
17. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum, 1997, 40(9):1725.
18. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum, 1982, 25(11):1271-1277.
19. Whiting P, Rutjes AW, Reitsma JB, et al. The development of QUADAS:a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol, 2003, 3:25.
20. Deville WL, Buntinx F, Bouter LM, et al. Conducting systematic reviews of diagnostic studies:didactic guidelines. BMC Med Res Methodol, 2002, 2:9.
21. Egger B, Schmid SW, Schafer M, et al.[2-year evaluation of a cooperation model between a surgical university clinic and a general hospital]. Chirurg, 2001, 72(1):30-36.
22. 郭珲, 罗静, 李荣山, 等. 抗核小体抗体与抗C1q抗体在狼疮肾炎血清的表达及其临床意义. 中华风湿病学杂志, 2005, 9(8):479-481.
23. 王琴, 杨铁生, 樊春红. 血清C1q抗体水平与系统性红斑狼疮活动性和狼疮肾炎的关系. 临床内科杂志, 2007, 24(4):238-240.
24. 罗宇鸿, 付俊, 张洪海. 联合检测血清中C1q抗体、IL-18对系统性红斑狼疮的诊断价值. 实用临床医学, 2009, 10(1):4-6, 9.
25. 王丽, 王琳. 狼疮肾炎患者血清自身抗体检测及意义. 中国基层医药, 2010, 17(21):2917-2918.
26. 冯江超, 青玉凤, 周京国. 血清抗C1q抗体在系统性红斑狼疮活动性判断及狼疮肾炎诊断中的价值. 免疫学杂志, 2010, (3):228-231.
27. 李娜, 李宝全, 巩路. 抗C1q抗体在系统性红斑狼疮及狼疮肾炎诊断中的作用. 天津医学大学学报, 2011, 17(4):546-548.
28. 崔婵娟, 柏明见, 冯珍如, 等. 血清抗C1q抗体在评价系统性红斑活动性及狼疮性肾炎病理分型中的临床意义. 中国全科医学, 2014, 17(17):1989-1993.
29. Tan Y, Zhou W, Yu F, et al. Detection of anti-C1q antibodies and anti-C1q globular head domain antibodies in sera from Chinese patients with lupus nephritis. Mol Immunol, 2009, 46(11-12):2178-2182.
30. Fang QY, Yu F, Tan Y, et al. Anti-C1q antibodies and IgG subclass distribution in sera from Chinese patients with lupus nephritis. Nephrol Dial Transplant, 2009, 24(1):172-178.
31. Wu FQ, Zhao Q, Cui XD, et al. C1q and anti-C1q antibody levels are correlated with disease severity in Chinese pediatric systemic lupus erythematosus. Rheumatol Int, 2011, 31(4):501-505.
32. Zhang CQ, Ren L, Gao F, et al. Anti-C1q antibodies are associated with systemic lupus erythematosus disease activity and lupus nephritis in northeast of China. Clin Rheumatol, 2011, 30(7):967-973.
33. Botto M, Dell'Agnola C, Bygrave AE, et al. Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat Genet, 1998, 19(1):56-59.
34. Tsacheva I, Radanova M, Todorova N, et al. Detection of autoantibodies against the globular domain of human C1q in the sera of systemic lupus erythematosus patients. Mol Immunol, 2007, 44(8):2147-2151.
35. Coremans IE, Daha MR, van der Voort EA, et al. Antibodies against C1q in anti-glomerular basement membrane nephritis. Clin Exp Immunol, 1992, 87(2):256-260.
36. Mahler M, van Schaarenburg RA, Trouw LA. Anti-C1q autoantibodies, novel tests, and clinical consequences. Front Immunol, 2013, 5(4):117.
37. Moura CG, Lima I, Barbosa L, et al. Anti-C1q antibodies:association with nephritis and disease activity in systemic lupus erythematosus. J Clin Lab Anal, 2009, 23(1):19-23.
38. Moroni G, Quaglini S, Radice A, et al. The value of a panel of autoantibodies for predicting the activity of lupus nephritis at time of renal biopsy. J Immunol Res, 2015, 2015:106904.
39. Oelzner P, Deliyska B, Funfstuck R, et al. Anti-C1q antibodies and antiendothelial cell antibodies in systemic lupus erythematosus-relationship with disease activity and renal involvement. Clin Rheumatol, 2003, 22(4-5):271-278.
40. Grootscholten C, Dieker JW, McGrath FD, et al. A prospective study of anti-chromatin and anti-C1q autoantibodies in patients with proliferative lupus nephritis treated with cyclophosphamide pulses or azathioprine/methylprednisolone. Ann Rheum Dis, 2007, 66(5):693-696.
41. Yang XW, Tan Y, Yu F, et al. Combination of anti-C1q and anti-dsDNA antibodies is associated with higher renal disease activity and predicts renal prognosis of patients with lupus nephritis. Nephrol Dial Transplant, 2012, 27(9):3552-3559.

Chinese Journal of Evidence-Based Medicine

Diagnostic Value of Serum anti-C1q Antibodies for Lupus Nephritis in Chinese Population: A Meta-analysis

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