刘毅,
Email: yi2006liu@163.com
狼疮肾炎是系统性红斑狼疮标志性特征之一，可见于40%～60%的患者，其特点是复发与缓解交替。肾脏穿刺活体组织检查是评估肾损害和疾病活动的金标准，但其为侵入性检测手段，并且有出血及感染的风险，不是十分适用于狼疮肾炎疾病活动性的监测。因此不少学者尝试通过一些无创或者微创的检测方法来评估狼疮肾炎疾病活动，而尿液凭借其具有容易获得性、并且可通过非侵入性途径获取的特点而成为研究的热点。目前这方面的研究主要集中在对狼疮肾炎患者尿液中生物标志物的研究，包括检测尿液中的趋化因子、细胞因子等，通过各种相关的检测手段以期发现一些关键的生物标志物来反映狼疮肾炎疾病活动性，已有一些生物标志物包括17相关细胞因子、叉头状转录因子、单核细胞趋化蛋白-1 等被报道和狼疮肾炎疾病活动有比较密切的关系。
Citation： 杜霁儒, 刘毅. 评估狼疮肾炎活动性尿液标志物的研究进展. West China Medical Journal, 2015, 30(7): 1369-1373. doi: 10.7507/1002-0179.20150395 Copy
| 1. | Peschken CA, Katz SJ, Silverman E, et al. The 1 000 Canadian faces of lupus:determinants of disease outcome in a large multiethnic cohort[J]. J Rheumatol, 2009, 36(6):1200-1208. |
| 2. | Moore RA, Derry S. Systematic review and meta-analysis of randomised trials and cohort studies of mycophenolate mofetil in lupus nephritis[J]. Arthritis Res Ther, 2006, 8(6):R182. |
| 3. | Linnik MD, Hu JZ, Heilbrunn KR, et al. Relationship between antidouble-stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus[J]. Arthritis Rheum, 2005, 52(4):1129-1137. |
| 4. | Goulet JR, Mackenzie T, Levinton C, et al. The longterm prognosis of lupus nephritis:the impact of disease activity[J]. J Rheumatol, 1993, 20(1):59-65. |
| 5. | Schiffenbauer J, Simon LS. Randomized controlled trials in systemic lupus erythematosus:what has been done and what do we need to do?[J]. Lupus, 2004, 13(5):398-405. |
| 6. | Foster MH, Kelley VR. Lupus nephritis:update on pathogenesis and disease mechanisms[J]. Semin Nephrol, 1999, 19(2):173-181. |
| 7. | Chan R, Lai F, Li E, et al. Imbalance of Th1/Th2 transcription factors in patients with lupus nephritis[J]. Rheumatology, 2006, 45(8):951-957. |
| 8. | Chan R, Lai F, Li E, et al. Expression of T-bet, a type 1 T-helper cell transcription factor, in the urinary sediment of lupus patients predicts disease flare[J]. Rheumatology, 2007, 46(1):44-48. |
| 9. | Horwitz DA, Gray JD, Behrendsen SC, et al. Decreased production of interleukin-12 and other Th1-type cytokines in patients with recent-onset systemic lupus erythematosus[J]. Arthritis Rheum, 1998, 41(5):838-844. |
| 10. | Akahoshi M, Nakashima H, Tanaka Y, et al. Th1/Th2 balance of peripheral T helper cells in systemic lupus erythematosus[J]. Arthritis Rheum, 1999, 42(8):1644-1648. |
| 11. | Steinman L. A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage[J]. Nat Med, 2007, 13(2):139-145. |
| 12. | Hernández-Cruz B, Tapia N, Villa-Romero AR, et al. Risk factors associated with mortality in systemic lupus erythematosus. A casecontrol study in a tertiary care center in Mexico City[J]. Clin Exp Rheumatol, 2001, 19(4):395-401. |
| 13. | Kwan BC, Tam LS, Lai KB, et al. The gene expression of type 17 T-helper cell-related cytokines in the urinary sediment of patients with systemic lupus erythematosus[J]. Rheumatology (Oxford), 2009, 48(12):1491-1497. |
| 14. | Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells[J]. Nat Immunol, 2003, 4(4):330-336. |
| 15. | Sakaguchi S. Naturally arising Foxp3-expressing CD25 + CD4+regulatory T cells in immunological tolerance to self and nonself[J]. Nat Immunol, 2005, 6(4):345-352. |
| 16. | Lee JH, Wang LC, Lin YT, et al. Inverse correlation between CD4+ regulatory T-cell population and autoantibody levels in paediatric patients with systemic lupus erythematosus[J]. Immunology, 2006, 117(2):280-286. |
| 17. | Valencia X, Yarboro C, Illei G, et al. Deficient CD4+CD25 high T regulatory cell function in patients with active systemic lupus erythematosus[J]. J Immunol, 2007, 178(4):2579-2588. |
| 18. | Lyssuk EY, Torgashina AV, Soloviev SK, et al. Reduced number and function of CD4+ CD25 high FoxP3+ regulatory T cells in patients with systemic lupus erythematosus[M]//Shurin MR, Smolkin YS. Immune-Mediated Diseases. New York:Springer, 2007:113-119. |
| 19. | Banham AH, Powrie FM, Suri-Payer E. FOXP3+ regulatory T cells:current controversies and future perspectives[J]. Eur J Immunol, 2006, 36(11):2832-2836. |
| 20. | Bonelli M, Von Dalwigk K, Savitskaya A, et al. Foxp3 expression in CD4+ T cells of patients with systemic lupus erythematosus:a comparative phenotypic analysis[J]. Ann Rheum Dis, 2008, 67(5):664-671. |
| 21. | Wang G, Lai FM, Tam LS, et al. Urinary FOXP3 mRNA in patients with lupus nephritis——relation with disease activity and treatment response[J]. Rheumatology (Oxford), 2009, 48(7):755-760. |
| 22. | Chan RW, Lai FM, Li EK, et al. Intrarenal cytokine gene expression in lupus nephritis[J]. Ann Rheum Dis, 2007, 66(7):886-892. |
| 23. | Dai C, Liu Z, Zhou H, et al. Monocyte chemoattractant protein-1 expression in renal tissue is associated with monocyte recruitment and tubulo-interstitial lesions in patients with lupus nephritis[J]. Chin Med J, 2001, 114(8):864-868. |
| 24. | Wada T, Yokoyama H, Su SB, et al. Monitoring urinary levels of monocyte chemotactic and activating factor reffects disease activity of lupus nephritis[J]. Kidney Int, 1996, 49(3):761-767. |
| 25. | El-Shehaby A, Darweesh H, El-Khatib M, et al. Correlations of urinary biomarkers, TNF-like weak inducer of apoptosis (TWEAK), osteoprotegerin (OPG), monocyte chemoattractant protein-1 (MCP-1), and IL-8 with lupus nephritis[J]. J Clin Immunol, 2011, 31(5):848-856. |
| 26. | Rovin BH, Song H, Birmingham DJ, et al. Urine chemokines as biomarkers of human systemic lupus erythematosus activity[J]. J Am Soc Nephrol, 2005, 16(2):467-473. |
| 27. | Abujam B, Cheekatla S, Aggarwal A. Urinary CXCL-10/IP-10 and MCP-1 as markers to assess activity of lupus nephritis[J]. Lupus, 2013, 22(6):614-623. |
| 28. | Lu J, Kwan BC, Lai FM, et al. Gene expression of TWEAK/Fn14 and IP-10/CXCR3 in glomerulus and tubulointerstitium of patients with lupus nephritis[J]. Nephrology (Carlton), 2011, 16(4):426-432. |
| 29. | Schwartz N, Rubinstein T, Burkly LC, et al. Urinary TWEAK as a biomarker of lupus nephritis:a multicenter cohort study[J]. Arthritis Res Ther, 2009, 11(5):R143. |
| 30. | Schwartz N, Su L, Burkly LC, et al. Urinary TWEAK and the activity of lupus nephritis[J]. J Autoimmun, 2006, 27(4):242-250. |
| 31. | Xuejing Z, Jiazhen T, Jun L, et al. Urinary TWEAK level as a marker of lupus nephritis activity in 46 cases[J]. J Biomed Biotechnol, 2012(6):359647. |
| 32. | Dai Y, Huang YS, Tang M, et al. Microarray analysis of microRNA expression in peripheral blood cells of systemic lupus erythematosus patients[J]. Lupus, 2007, 16(12):939-946. |
| 33. | Dai Y, Sui W, Lan H, et al. Comprehensive analysis of microRNA expression patterns in renal biopsies of lupus nephritis patients[J]. Rheumatol Int, 2009, 29(7):749-754. |
| 34. | Cortez MA, Calin GA. MicroRNA identification in plasma and serum:a new tool to diagnose and monitor diseases[J]. Expert Opin Biol Ther, 2009, 9(6):703-711. |
| 35. | Pauley KM, Cha S, Chan EK. MicroRNA in autoimmunity and autoimmune diseases[J]. J Autoimmun, 2009, 32(3/4):189-194. |
| 36. | Lu LF, Liston A. MicroRNA in the immune system, microRNA as an immune system[J]. Immunology, 2009, 127(3):291-298. |
| 37. | Liang TJ, Qin CY. The emerging role of microRNAs in immune cell development and differentiation[J]. APMIS, 2009, 117(9):635-643. |
| 38. | Wang G, Tam LS, Kwan BC, et al. Expression of miR-146a and miR-155 in the urinary sediment of systemic lupus erythematosus[J]. Clin Rheumatol, 2012, 31(3):435-440. |
| 39. | Wang G, Tam LS, Li EK, et al. Serum and urinary cell-free MiR-146a and MiR-155 in patients with systemic lupus erythematosus[J]. J Rheumatol, 2010, 37(12):2516-2522. |
| 40. | Gong AY, Hu G, Zhou R, et al. MicroRNA-221 controls expression of intercellular adhesion molecule-1 in epithelial cells in response to Cryptosporidium parvum infection[J]. Int J Parasitol, 2011, 41(3/4):397-403. |
| 41. | Hu G, Gong AY, Liu J, et al. miR-221 suppresses ICAM-1 translation and regulates interferon-gamma-induced ICAM-1 expression in human cholangiocytes[J]. Am J Physiol Gastrointest Liver Physiol, 2010, 298(4):G542-G550. |
| 42. | Ueda R, Kohanbash G, Sasaki K, et al. Dicer-regulated microRNAs 222 and 339 promote resistance of cancer cells to cytotoxic T-lymphocytes by down-regulation of ICAM-1[J]. Proc Natl Acad Sci USA, 2009, 106(26):10746-10751. |
| 43. | Urbich C, Kuehbacher A, Dimmeler S. Role of microRNAs in vascular diseases, inflammation, and angiogenesis[J]. Cardiovasc Res, 2008, 79(4):581-588. |
| 44. | Zhu N, Zhang D, Chen S, et al. Endothelial enriched microRNAs regulate angiotensinⅡ-induced endothelial inflammation and migration[J]. Atherosclerosis, 2011, 215(2):286-293. |
| 45. | Trachtman H, Christen E, Cnaan A, et al. Urinary neutrophil gelatinase-associated lipocalcin in D+HUS:a novel marker of renal injury[J]. Pediatr Nephrol, 2006, 21(7):989-994. |
| 46. | Mishra J, Mori K, Ma Q, et al. Neutrophil gelatinase-associated lipocalin:a novel early urinary biomarker for cisplatin nephrotoxicity[J]. Am J Nephrol, 2004, 24(3):307-315. |
| 47. | Malyszko J, Malyszko JS, Bachorzewska-Gajewska H, et al. Neutrophil gelatinase-associated lipocalin is a new and sensitive marker of kidney function in chronic kidney disease patients and renal allograft recipients[J]. Transplant Proc, 2009, 41(1):158-161. |
| 48. | Brunner HI, Mueller M, Rutherford C, et al. Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus[J]. Arthritis Rheum, 2006, 54(8):2577-2584. |
| 49. | Pitashny M, Schwartz N, Qing X, et al. Urinary lipocalin-2 is associated with renal disease activity in human lupus nephritis[J]. Arthritis Rheum, 2007, 56(6):1894-1903. |
| 50. | Rubinstein T, Pitashny M, Levine B, et al. Urinary neutrophil gelatinase-associated lipocalin as a novel biomarker for disease activity in lupus nephritis[J]. Rheumatology (Oxford), 2010, 49(5):960-971. |
| 51. | Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000[J]. J Rheumatol, 2002, 29(2):288-291. |
| 52. | Yilmaz A, Sevketoglu E, Gedikbasi A, et al. Early prediction of urinary tract infection with urinary neutrophil gelatinase associated lipocalin[J]. Pediatr Nephrol, 2009, 24(12):2387-2392. |
- 1. Peschken CA, Katz SJ, Silverman E, et al. The 1 000 Canadian faces of lupus:determinants of disease outcome in a large multiethnic cohort[J]. J Rheumatol, 2009, 36(6):1200-1208.
- 2. Moore RA, Derry S. Systematic review and meta-analysis of randomised trials and cohort studies of mycophenolate mofetil in lupus nephritis[J]. Arthritis Res Ther, 2006, 8(6):R182.
- 3. Linnik MD, Hu JZ, Heilbrunn KR, et al. Relationship between antidouble-stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus[J]. Arthritis Rheum, 2005, 52(4):1129-1137.
- 4. Goulet JR, Mackenzie T, Levinton C, et al. The longterm prognosis of lupus nephritis:the impact of disease activity[J]. J Rheumatol, 1993, 20(1):59-65.
- 5. Schiffenbauer J, Simon LS. Randomized controlled trials in systemic lupus erythematosus:what has been done and what do we need to do?[J]. Lupus, 2004, 13(5):398-405.
- 6. Foster MH, Kelley VR. Lupus nephritis:update on pathogenesis and disease mechanisms[J]. Semin Nephrol, 1999, 19(2):173-181.
- 7. Chan R, Lai F, Li E, et al. Imbalance of Th1/Th2 transcription factors in patients with lupus nephritis[J]. Rheumatology, 2006, 45(8):951-957.
- 8. Chan R, Lai F, Li E, et al. Expression of T-bet, a type 1 T-helper cell transcription factor, in the urinary sediment of lupus patients predicts disease flare[J]. Rheumatology, 2007, 46(1):44-48.
- 9. Horwitz DA, Gray JD, Behrendsen SC, et al. Decreased production of interleukin-12 and other Th1-type cytokines in patients with recent-onset systemic lupus erythematosus[J]. Arthritis Rheum, 1998, 41(5):838-844.
- 10. Akahoshi M, Nakashima H, Tanaka Y, et al. Th1/Th2 balance of peripheral T helper cells in systemic lupus erythematosus[J]. Arthritis Rheum, 1999, 42(8):1644-1648.
- 11. Steinman L. A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage[J]. Nat Med, 2007, 13(2):139-145.
- 12. Hernández-Cruz B, Tapia N, Villa-Romero AR, et al. Risk factors associated with mortality in systemic lupus erythematosus. A casecontrol study in a tertiary care center in Mexico City[J]. Clin Exp Rheumatol, 2001, 19(4):395-401.
- 13. Kwan BC, Tam LS, Lai KB, et al. The gene expression of type 17 T-helper cell-related cytokines in the urinary sediment of patients with systemic lupus erythematosus[J]. Rheumatology (Oxford), 2009, 48(12):1491-1497.
- 14. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells[J]. Nat Immunol, 2003, 4(4):330-336.
- 15. Sakaguchi S. Naturally arising Foxp3-expressing CD25 + CD4+regulatory T cells in immunological tolerance to self and nonself[J]. Nat Immunol, 2005, 6(4):345-352.
- 16. Lee JH, Wang LC, Lin YT, et al. Inverse correlation between CD4+ regulatory T-cell population and autoantibody levels in paediatric patients with systemic lupus erythematosus[J]. Immunology, 2006, 117(2):280-286.
- 17. Valencia X, Yarboro C, Illei G, et al. Deficient CD4+CD25 high T regulatory cell function in patients with active systemic lupus erythematosus[J]. J Immunol, 2007, 178(4):2579-2588.
- 18. Lyssuk EY, Torgashina AV, Soloviev SK, et al. Reduced number and function of CD4+ CD25 high FoxP3+ regulatory T cells in patients with systemic lupus erythematosus[M]//Shurin MR, Smolkin YS. Immune-Mediated Diseases. New York:Springer, 2007:113-119.
- 19. Banham AH, Powrie FM, Suri-Payer E. FOXP3+ regulatory T cells:current controversies and future perspectives[J]. Eur J Immunol, 2006, 36(11):2832-2836.
- 20. Bonelli M, Von Dalwigk K, Savitskaya A, et al. Foxp3 expression in CD4+ T cells of patients with systemic lupus erythematosus:a comparative phenotypic analysis[J]. Ann Rheum Dis, 2008, 67(5):664-671.
- 21. Wang G, Lai FM, Tam LS, et al. Urinary FOXP3 mRNA in patients with lupus nephritis——relation with disease activity and treatment response[J]. Rheumatology (Oxford), 2009, 48(7):755-760.
- 22. Chan RW, Lai FM, Li EK, et al. Intrarenal cytokine gene expression in lupus nephritis[J]. Ann Rheum Dis, 2007, 66(7):886-892.
- 23. Dai C, Liu Z, Zhou H, et al. Monocyte chemoattractant protein-1 expression in renal tissue is associated with monocyte recruitment and tubulo-interstitial lesions in patients with lupus nephritis[J]. Chin Med J, 2001, 114(8):864-868.
- 24. Wada T, Yokoyama H, Su SB, et al. Monitoring urinary levels of monocyte chemotactic and activating factor reffects disease activity of lupus nephritis[J]. Kidney Int, 1996, 49(3):761-767.
- 25. El-Shehaby A, Darweesh H, El-Khatib M, et al. Correlations of urinary biomarkers, TNF-like weak inducer of apoptosis (TWEAK), osteoprotegerin (OPG), monocyte chemoattractant protein-1 (MCP-1), and IL-8 with lupus nephritis[J]. J Clin Immunol, 2011, 31(5):848-856.
- 26. Rovin BH, Song H, Birmingham DJ, et al. Urine chemokines as biomarkers of human systemic lupus erythematosus activity[J]. J Am Soc Nephrol, 2005, 16(2):467-473.
- 27. Abujam B, Cheekatla S, Aggarwal A. Urinary CXCL-10/IP-10 and MCP-1 as markers to assess activity of lupus nephritis[J]. Lupus, 2013, 22(6):614-623.
- 28. Lu J, Kwan BC, Lai FM, et al. Gene expression of TWEAK/Fn14 and IP-10/CXCR3 in glomerulus and tubulointerstitium of patients with lupus nephritis[J]. Nephrology (Carlton), 2011, 16(4):426-432.
- 29. Schwartz N, Rubinstein T, Burkly LC, et al. Urinary TWEAK as a biomarker of lupus nephritis:a multicenter cohort study[J]. Arthritis Res Ther, 2009, 11(5):R143.
- 30. Schwartz N, Su L, Burkly LC, et al. Urinary TWEAK and the activity of lupus nephritis[J]. J Autoimmun, 2006, 27(4):242-250.
- 31. Xuejing Z, Jiazhen T, Jun L, et al. Urinary TWEAK level as a marker of lupus nephritis activity in 46 cases[J]. J Biomed Biotechnol, 2012(6):359647.
- 32. Dai Y, Huang YS, Tang M, et al. Microarray analysis of microRNA expression in peripheral blood cells of systemic lupus erythematosus patients[J]. Lupus, 2007, 16(12):939-946.
- 33. Dai Y, Sui W, Lan H, et al. Comprehensive analysis of microRNA expression patterns in renal biopsies of lupus nephritis patients[J]. Rheumatol Int, 2009, 29(7):749-754.
- 34. Cortez MA, Calin GA. MicroRNA identification in plasma and serum:a new tool to diagnose and monitor diseases[J]. Expert Opin Biol Ther, 2009, 9(6):703-711.
- 35. Pauley KM, Cha S, Chan EK. MicroRNA in autoimmunity and autoimmune diseases[J]. J Autoimmun, 2009, 32(3/4):189-194.
- 36. Lu LF, Liston A. MicroRNA in the immune system, microRNA as an immune system[J]. Immunology, 2009, 127(3):291-298.
- 37. Liang TJ, Qin CY. The emerging role of microRNAs in immune cell development and differentiation[J]. APMIS, 2009, 117(9):635-643.
- 38. Wang G, Tam LS, Kwan BC, et al. Expression of miR-146a and miR-155 in the urinary sediment of systemic lupus erythematosus[J]. Clin Rheumatol, 2012, 31(3):435-440.
- 39. Wang G, Tam LS, Li EK, et al. Serum and urinary cell-free MiR-146a and MiR-155 in patients with systemic lupus erythematosus[J]. J Rheumatol, 2010, 37(12):2516-2522.
- 40. Gong AY, Hu G, Zhou R, et al. MicroRNA-221 controls expression of intercellular adhesion molecule-1 in epithelial cells in response to Cryptosporidium parvum infection[J]. Int J Parasitol, 2011, 41(3/4):397-403.
- 41. Hu G, Gong AY, Liu J, et al. miR-221 suppresses ICAM-1 translation and regulates interferon-gamma-induced ICAM-1 expression in human cholangiocytes[J]. Am J Physiol Gastrointest Liver Physiol, 2010, 298(4):G542-G550.
- 42. Ueda R, Kohanbash G, Sasaki K, et al. Dicer-regulated microRNAs 222 and 339 promote resistance of cancer cells to cytotoxic T-lymphocytes by down-regulation of ICAM-1[J]. Proc Natl Acad Sci USA, 2009, 106(26):10746-10751.
- 43. Urbich C, Kuehbacher A, Dimmeler S. Role of microRNAs in vascular diseases, inflammation, and angiogenesis[J]. Cardiovasc Res, 2008, 79(4):581-588.
- 44. Zhu N, Zhang D, Chen S, et al. Endothelial enriched microRNAs regulate angiotensinⅡ-induced endothelial inflammation and migration[J]. Atherosclerosis, 2011, 215(2):286-293.
- 45. Trachtman H, Christen E, Cnaan A, et al. Urinary neutrophil gelatinase-associated lipocalcin in D+HUS:a novel marker of renal injury[J]. Pediatr Nephrol, 2006, 21(7):989-994.
- 46. Mishra J, Mori K, Ma Q, et al. Neutrophil gelatinase-associated lipocalin:a novel early urinary biomarker for cisplatin nephrotoxicity[J]. Am J Nephrol, 2004, 24(3):307-315.
- 47. Malyszko J, Malyszko JS, Bachorzewska-Gajewska H, et al. Neutrophil gelatinase-associated lipocalin is a new and sensitive marker of kidney function in chronic kidney disease patients and renal allograft recipients[J]. Transplant Proc, 2009, 41(1):158-161.
- 48. Brunner HI, Mueller M, Rutherford C, et al. Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus[J]. Arthritis Rheum, 2006, 54(8):2577-2584.
- 49. Pitashny M, Schwartz N, Qing X, et al. Urinary lipocalin-2 is associated with renal disease activity in human lupus nephritis[J]. Arthritis Rheum, 2007, 56(6):1894-1903.
- 50. Rubinstein T, Pitashny M, Levine B, et al. Urinary neutrophil gelatinase-associated lipocalin as a novel biomarker for disease activity in lupus nephritis[J]. Rheumatology (Oxford), 2010, 49(5):960-971.
- 51. Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000[J]. J Rheumatol, 2002, 29(2):288-291.
- 52. Yilmaz A, Sevketoglu E, Gedikbasi A, et al. Early prediction of urinary tract infection with urinary neutrophil gelatinase associated lipocalin[J]. Pediatr Nephrol, 2009, 24(12):2387-2392.