Rovin Brad H, Song Huijuan, Birmingham Dan J, Hebert Lee A, Yu Chack Yung, Nagaraja Haikady N
Ohio State University, Nephrology Division, N210 Means Hall, 1654 Upham Drive, Columbus, OH 43210, USA.
J Am Soc Nephrol. 2005 Feb;16(2):467-73. doi: 10.1681/ASN.2004080658. Epub 2004 Dec 15.
The purpose of this study was to evaluate urine monocyte chemoattractant protein-1 (MCP-1) and IL-8 as biomarkers of SLE flare. Urine was collected every 2 mo from patients who were followed prospectively in the Ohio SLE Study. Renal and nonrenal flares were identified and MCP-1 and IL-8 were measured by specific ELISA in samples that were collected at flare. When available, MCP-1 and IL-8 were also measured in urine samples before and after flare. For comparison, MCP-1 and IL-8 were measured in the urine of healthy individuals and in renal and nonrenal SLE patients with stable disease activity (disease controls). Most patients were receiving maintenance immunosuppressive therapy before flare. At renal flare, mean urine MCP-1 (uMCP-1) was significantly greater than uMCP-1 at nonrenal flare and from healthy volunteers and renal disease controls. The level of uMCP-1 correlated with the increase in proteinuria at flare and was higher in patients with proliferative glomerulonephritis and in patients with impaired renal function. Urine MCP-1 was increased beginning 2 to 4 mo before flare. Patients who responded to therapy showed a slow decline in uMCP-1 over several months, whereas nonresponders had persistently high uMCP-1. In contrast, uIL-8 did not change with disease activity and was not elevated at renal or nonrenal flare compared with disease controls. In conclusion, uMCP-1 but not uIL-8 is a sensitive and specific biomarker of renal SLE flare and its severity, even in patients who receive significant immunosuppressive therapy. Persistently elevated uMCP-1 after treatment may indicate ongoing kidney injury that may adversely affect renal prognosis.
本研究的目的是评估尿单核细胞趋化蛋白-1（MCP-1）和白细胞介素-8（IL-8）作为系统性红斑狼疮（SLE）病情复发生物标志物的价值。在俄亥俄州SLE研究中，对患者进行前瞻性随访，每2个月收集一次尿液。确定肾脏和非肾脏病情复发情况，并通过特异性酶联免疫吸附测定（ELISA）法检测复发时采集样本中的MCP-1和IL-8。如有可能，还在病情复发前后的尿液样本中检测MCP-1和IL-8。作为对照，检测健康个体以及病情活动稳定的肾脏和非肾脏SLE患者（疾病对照组）尿液中的MCP-1和IL-补体8。大多数患者在病情复发前接受维持性免疫抑制治疗。在肾脏病情复发时，尿MCP-1（uMCP-1）均值显著高于非肾脏病情复发时、健康志愿者以及肾脏疾病对照组的uMCP-1。uMCP-1水平与复发时蛋白尿的增加相关，在增殖性肾小球肾炎患者和肾功能受损患者中更高。尿液MCP-1在病情复发前2至4个月开始升高。对治疗有反应的患者在数月内uMCP-1缓慢下降，而无反应者的uMCP-1持续处于高位。相比之下，尿IL-8（uIL-8）不随疾病活动而变化，与疾病对照组相比，在肾脏或非肾脏病情复发时也未升高。总之，即使在接受显著免疫抑制治疗的患者中，uMCP-1而非uIL-8是肾脏SLE病情复发及其严重程度的敏感且特异的生物标志物。治疗后uMCP-1持续升高可能表明存在持续的肾损伤，这可能对肾脏预后产生不利影响。
