狼疮性肾炎的生物标志物研究进展

doi:10.3877/cma.j.issn.2095-3216.2022.03.009

狼疮性肾炎(LN)是系统性红斑狼疮(SLE)最常见和最严重的表现之一，20%~60%的SLE患者会出现肾脏损伤。抗双链DNA抗体、补体成分C3和C4、尿蛋白肌酐比值等作为LN诊断传统生物标志物，在监测疾病活动和早期肾脏病理损害方面缺乏特异性和敏感性。LN诊断的金标准是肾组织病理活检，这是一种有创检查，不利于早期诊断和反复监测。寻找能替代肾组织病理活检的新型生物标志物，对早期诊断、疾病活动监测、改善预后具有重要意义。本文总结了血液和尿液中新型生物标志物的研究进展，并对其临床应用前景提出展望，为临床诊断工作提供理论支持。

关键词: 狼疮性肾炎, 新型生物标志物, 传统生物标志物, 血液, 尿液

Lupus nephritis (LN) is one of the most common and serious manifestations of systemic lupus erythematosus (SLE). Kidney damage occurs in 20% to 60% of patients with SLE. As traditional biomarkers for LN diagnosis, anti-double-stranded DNA antibodies, complement components C3 and C4, and urine protein-creatinine ratio, etc., lack specificity and sensitivity in monitoring disease activity and early renal pathological damage. The gold standard for LN diagnosis is pathological biopsy of renal tissue, which is an invasive examination that is not suitable for early diagnosis and repeated monitoring. Finding novel biomarkers that can replace renal biopsy is of great significance for early diagnosis, monitoring of disease activity, and improving prognosis. This paper summarized the research progress for novel biomarkers in blood and urine, and put forward the prospect of their clinical application, providing theoretical support for clinical diagnosis.

Key words: Lupus nephritis, Novel biomarkers, Traditional biomarkers, Blood, Urine

表1 狼疮性肾炎的生物标志物

组别		组份	表达		引用文献
传统生物标志物		补体蛋白	C3, C4	减少	[5，6，7]
		自身抗体	抗dsDNA抗体	增加	[8，9，10]
			抗核小体抗体	增加	[12，13]
			抗Sm抗体	增加	[14，15]
			抗核糖核蛋白抗体	增加	[14，16]
			抗磷脂抗体	增加	[17，18]
			尿蛋白/肌酐比值	增加	[19，20]
新型生物标志物	尿液中新型生物标志物	黏附分子	VCAM-1	增加	[22，23]
			ICAM-1	增加	[23，24，25]
		生长因子	PDGF-Rβ	增加	[26]
			TGF-β1	增加	[27，28]
		趋化因子	MCP-1	增加	[29，30]
		miRNAs	miR-3201, miR-1273e, miR-654	减少	[32，34]
			miR-21, miR-155	增加	[33]
		其他新型生物标志物	NGAL	增加	[30，35]
			ACT	增加	[36]
			纤溶酶	增加	[37]
			CD163	增加	[41，42，43]
	血液中新型生物标志物	细胞因子	IL-25	增加	[44，45]
			IFN-Ⅰ	增加	[47，48]
		趋化因子	CCL2, CCL4, CCL5, CXCL10, CXCL12	增加	[49，50]
		脂肪分子	ADPN	增加	[51，52]
		自身抗体	抗C1q抗体	增加	[10，53]

表1 狼疮性肾炎的生物标志物

组别		组份	表达		引用文献
传统生物标志物		补体蛋白	C3, C4	减少	[5，6，7]
		自身抗体	抗dsDNA抗体	增加	[8，9，10]
			抗核小体抗体	增加	[12，13]
			抗Sm抗体	增加	[14，15]
			抗核糖核蛋白抗体	增加	[14，16]
			抗磷脂抗体	增加	[17，18]
			尿蛋白/肌酐比值	增加	[19，20]
新型生物标志物	尿液中新型生物标志物	黏附分子	VCAM-1	增加	[22，23]
			ICAM-1	增加	[23，24，25]
		生长因子	PDGF-Rβ	增加	[26]
			TGF-β1	增加	[27，28]
		趋化因子	MCP-1	增加	[29，30]
		miRNAs	miR-3201, miR-1273e, miR-654	减少	[32，34]
			miR-21, miR-155	增加	[33]
		其他新型生物标志物	NGAL	增加	[30，35]
			ACT	增加	[36]
			纤溶酶	增加	[37]
			CD163	增加	[41，42，43]
	血液中新型生物标志物	细胞因子	IL-25	增加	[44，45]
			IFN-Ⅰ	增加	[47，48]
		趋化因子	CCL2, CCL4, CCL5, CXCL10, CXCL12	增加	[49，50]
		脂肪分子	ADPN	增加	[51，52]
		自身抗体	抗C1q抗体	增加	[10，53]

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Research progress in biomarkers of lupus nephritis

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