1 Immunology, King's College Hospital, London, UK.
2 Immunology, Guy's & St Thomas' Hospitals, London, UK.
Lupus. 2019 May;28(6):713-721. doi: 10.1177/0961203319845487. Epub 2019 May 2.
Current non-invasive methods of assessing disease activity in systemic lupus erythematosus (SLE) are of limited sensitivity and specificity. Testing includes acute phase markers, autoantibodies and complement levels. Although measurements of dsDNA antibodies and complement C3/C4 levels are routine, they remain of limited value. Improved blood and urine markers may help in early detection of flare, distinction between flare and chronic damage, and monitoring response to therapy.
A total of 87 patients with SLE were tested for the following cytokines in serum and urine: monocyte chemoattractant protein 1 (MCP-1), regulated upon activation, normal T cell expressed and secreted (RANTES), soluble tumour necrosis factor receptor 1 (sTNF-R1), interferon-inducible protein 10 (IP-10), monocyte inhibitory protein 1α (MIP-1α) and vascular endothelial growth factor (VEGF). Patients attending the Lupus Unit at St Thomas' Hospital, London, UK were divided into active lupus nephritis (LN), inactive LN and non-renal SLE groups based on their renal pathology and SLE disease activity index (SLEDAI). Cytokine testing was performed using the FIDIS multiplex bead assay.
The mean level of serum sTNF-R1 was higher in the active LN group compared with both inactive LN and non-renal SLE groups ( p < 0.001). For urine measurements there were significant differences between active LN and non-renal SLE for VEGF ( p = 0.016), after statistical correction for multiple testing. Both urinary and serum sTNF-R1 and IP-10 levels correlated with SLEDAI scores ( p < 0.001), while serum VEGF correlated weakly with SLEDAI ( p = 0.025). The optimum combination for differentiating active from inactive LN patients was serum VEGF, sTNF-R1, MCP-1 and glomerular filtration rate plus urinary sTNF-R1 and protein-creatinine ratio.
These results indicate that for active LN, sTNF-R1 could be a useful serum cytokine marker, with potential for VEGF in the urine. This study has confirmed the ability of the multiplex bead technique to detect cytokines in a good analytical range, including very low and high levels, in both serum and urine. Combining serum and urine markers provided additional sensitivity in distinguishing active from inactive LN.
目前，评估系统性红斑狼疮（SLE）疾病活动的非侵入性方法的灵敏度和特异性均有限。检测包括急性期标志物、自身抗体和补体水平。虽然 dsDNA 抗体和补体 C3/C4 水平的测量是常规的，但它们的价值仍然有限。改进的血液和尿液标志物可能有助于早期发现疾病活动，区分疾病活动与慢性损害，并监测治疗反应。
共检测了 87 例 SLE 患者的血清和尿液中的以下细胞因子：单核细胞趋化蛋白 1（MCP-1）、活化正常 T 细胞表达和分泌因子（RANTES）、可溶性肿瘤坏死因子受体 1（sTNF-R1）、干扰素诱导蛋白 10（IP-10）、单核细胞抑制蛋白 1α（MIP-1α）和血管内皮生长因子（VEGF）。英国伦敦圣托马斯医院狼疮科的患者根据肾脏病理和系统性红斑狼疮疾病活动指数（SLEDAI）分为狼疮性肾炎（LN）活动组、LN 不活动组和非肾脏 SLE 组。细胞因子检测采用 FIDIS 多重珠粒检测法。
与 LN 不活动组和非肾脏 SLE 组相比，LN 活动组患者血清 sTNF-R1 水平较高（p<0.001）。尿液测量中，VEGF 在 LN 活动组与非肾脏 SLE 组之间存在显著差异（p=0.016），但经多次检测校正后无统计学意义。血清和尿液 sTNF-R1 及 IP-10 水平与 SLEDAI 评分均相关（p<0.001），而血清 VEGF 与 SLEDAI 评分相关较弱（p=0.025）。用于区分 LN 活动组与不活动组患者的最佳组合是血清 VEGF、sTNF-R1、MCP-1 和肾小球滤过率以及尿液 sTNF-R1 和蛋白-肌酐比。
这些结果表明，对于 LN 活动组，sTNF-R1 可能是一种有用的血清细胞因子标志物，尿液中 VEGF 也有潜在的作用。本研究证实了多重珠粒技术能够在良好的分析范围内检测血清和尿液中的细胞因子，包括非常低和高水平的细胞因子。联合血清和尿液标志物可提高区分 LN 活动组与不活动组的敏感性。
