Go D J, Lee J Y, Kang M J, Lee E Y, Lee E B, Yi E C, Song Y W
1 Division of Rheumatology, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea.
2 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine, Medical Research Institute, Seoul National University, Seoul, Korea.
Lupus. 2018 Sep;27(10):1600-1615. doi: 10.1177/0961203318778774. Epub 2018 Jun 29.
Lupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE). Conventional biomarkers for assessing renal disease activity are imperfect in predicting clinical outcomes associated with LN. The aim of this study is to identify urinary protein biomarkers that reliably reflect the disease activity or predict clinical outcomes. A quantitative proteomic analysis was performed to identify protein biomarker candidates that can differentiate between SLE patients with and without LN. Selected biomarker candidates were further verified by enzyme-linked immunosorbent assay using urine samples from a larger cohort of SLE patients ( n = 121) to investigate their predictive values for LN activity measure. Furthermore, the association between urinary levels of a selected panel of potential biomarkers and prognosis of LN was assessed with a four-year follow-up study of renal outcomes. Urinary vitamin D-binding protein (VDBP), transthyretin (TTR), retinol binding protein 4 (RBP4), and prostaglandin D synthase (PTGDS) were significantly elevated in SLE patients with LN, especially in patients with active LN ( n = 21). Among them, VDBP well correlated with severity of proteinuria (rho = 0.661, p < 0.001) and renal SLE Disease Activity Index (renal SLEDAI) (rho = 0.520, p < 0.001). In the four-year follow-up, VDBP was a significant risk factor (hazard ratio 9.627, 95% confidence interval 1.698 to 54.571, p = 0.011) for the development of proteinuric flare in SLE patients without proteinuria ( n = 100) after adjustments for multiple confounders. Urinary VDBP correlated with proteinuria and renal SLEDAI, and predicted the development of proteinuria.
狼疮性肾炎（LN）是系统性红斑狼疮（SLE）的主要并发症。用于评估肾脏疾病活动的传统生物标志物在预测与LN相关的临床结局方面并不理想。本研究的目的是鉴定能够可靠反映疾病活动或预测临床结局的尿蛋白生物标志物。进行了定量蛋白质组学分析，以鉴定可区分有和无LN的SLE患者的蛋白质生物标志物候选物。使用来自更大队列的SLE患者（n = 121）的尿液样本，通过酶联免疫吸附测定进一步验证选定的生物标志物候选物，以研究它们对LN活动指标的预测价值。此外，通过对肾脏结局进行为期四年的随访研究，评估了一组选定的潜在生物标志物的尿液水平与LN预后之间的关联。在有LN的SLE患者中，尤其是在活动性LN患者（n = 21）中，尿维生素D结合蛋白（VDBP）、转甲状腺素蛋白（TTR）、视黄醇结合蛋白4（RBP4）和前列腺素D合酶（PTGDS）显著升高。其中，VDBP与蛋白尿严重程度（rho = 0.661，p < 0.001）和肾脏SLE疾病活动指数（renal SLEDAI）（rho = 0.520，p < 0.001）密切相关。在四年的随访中，在对多个混杂因素进行调整后，VDBP是无蛋白尿的SLE患者（n = 100）发生蛋白尿复发的重要危险因素（风险比9.627，95%置信区间1.698至54.571，p = 0.011）。尿VDBP与蛋白尿和renal SLEDAI相关，并可预测蛋白尿的发生。
