BACKGROUND Lupus nephritis (LN) is the most common organ manifestation in systemic lupus erythematosus (SLE) and associated with a poor prognosis. Still, a noninvasive but reliable method to diagnose LN has not been established. Thus, we evaluated whether blood sphingolipids could serve as valid biomarkers for renal injury. METHODS In this cross-sectional study, 82 participants were divided into three groups: 36 healthy controls and 17 SLE patients without renal injury (both: estimated glomerular filtration rate (eGFR) ≥ 80 ml/min/1.73 m2 and albumin/creatinine ≤ 30 mg/g) and 29  LN patients. LN patients were identified by renal biopsies and impaired renal function (eGFR < 80 ml/min/1.73 m2 and albumin/creatinine ratio > 30 mg/g). Venous blood was collected from all participants and sphingolipid levels in plasma and serum were measured by LC-MS/MS. RESULTS Most interesting, concentrations of some specific ceramides, C16ceramide (Cer), C18Cer, C20Cer and C24:1Cer, were elevated in both, plasma and serum samples of patients suffering from biopsy-proven LN and impaired renal function, compared to healthy controls as well as SLE patients without renal injury. C24:1dhCer levels were elevated in plasma and serum samples from LN patients compared to SLE patients. Sphingosine levels were higher in plasma and serum of LN patients compared to healthy controls, but not compared to SLE patients. Sphinganine concentrations were significantly elevated in serum samples from LN patients compared to healthy controls and SLE. S1P and SA1P levels were higher in plasma samples of SLE and LN patients compared to healthy controls. Subsequent ROC analyses of plasma and serum data of the most altered ceramide species (C16Cer, C18Cer, C20Cer, C24:1Cer) between LN patients and SLE patients display a high diagnostic differentiation with significant AUCs especially for C24:1Cer serum levels. Further, C24:1Cer serum levels were not affected by glucocorticoid treatment and did not correlate with other renal markers, such as serum creatinine, eGFR and albumin/creatinine ratio. CONCLUSION Our data reveal that chain-length specific ceramides in blood, most likely C24:1Cer levels in serum, could act as potent biomarkers for renal impairment in patients suffering from SLE.

中文翻译：

---

血液神经酰胺是系统性红斑狼疮肾功能损害的新标记。

背景技术狼疮性肾炎（LN）是系统性红斑狼疮（SLE）中最常见的器官表现，且预后较差。仍然没有建立诊断LN的非侵入性但可靠的方法。因此，我们评估了血液鞘脂是否可以作为肾损伤的有效生物标志物。方法在这项横断面研究中，将82名参与者分为三组：36名健康对照者和17名无肾损伤的SLE患者（均：估计肾小球滤过率（eGFR）≥80 ml / min / 1.73 m2和白蛋白/肌酐≤30 mg / g）和29名LN患者。LN患者通过肾活检和肾功能受损（eGFR <80 ml / min / 1.73 m2和白蛋白/肌酐比> 30 mg / g）进行鉴定。从所有参与者收集静脉血，并通过LC-MS / MS测量血浆和血清中的鞘脂水平。结果最有趣的是，与活检证实的LN和肾功能受损的患者相比，血浆和血清样本中某些特定的神经酰胺，C16神经酰胺（Cer），C18Cer，C20Cer和C24：1Cer的浓度均升高。以及没有肾损伤的SLE患者。与SLE患者相比，LN患者的血浆和血清样本中C24：1dhCer水平升高。与健康对照组相比，LN患者血浆和血清中的鞘氨醇水平更高，但与SLE患者相比则没有。与健康对照组和SLE相比，LN患者血清样本中的Sphinganine浓度显着升高。与健康对照组相比，SLE和LN患者血浆样品中的S1P和SA1P水平更高。随后对LN患者和SLE患者之间神经酰胺种类变化最大的血浆和血清数据进行ROC分析（C16Cer，C18Cer，C20Cer，C24：1Cer），显示出高度的诊断差异性，尤其是C24：1Cer血清水平具有显着的AUC。此外，C24：1Cer血清水平不受糖皮质激素治疗的影响，并且与其他肾标志物（例如血清肌酐，eGFR和白蛋白/肌酐比值）不相关。结论我们的数据表明，血液中特定链长的神经酰胺，很可能是血清中C24：1Cer的水平，可以作为SLE患者肾功能损害的有效生物标志物。随后对LN患者和SLE患者之间神经酰胺种类变化最大的血浆和血清数据进行ROC分析（C16Cer，C18Cer，C20Cer，C24：1Cer），显示出高度的诊断差异性，尤其是C24：1Cer血清水平具有显着的AUC。此外，C24：1Cer血清水平不受糖皮质激素治疗的影响，并且与其他肾标志物（例如血清肌酐，eGFR和白蛋白/肌酐比值）不相关。结论我们的数据表明，血液中特定链长的神经酰胺，最有可能是血清中C24：1Cer的水平，可以作为SLE患者肾功能损害的有效生物标志物。随后对LN患者和SLE患者之间神经酰胺种类变化最大的血浆和血清数据进行ROC分析（C16Cer，C18Cer，C20Cer，C24：1Cer），显示出高度的诊断差异性，尤其是C24：1Cer血清水平具有显着的AUC。此外，C24：1Cer血清水平不受糖皮质激素治疗的影响，并且与其他肾标志物（例如血清肌酐，eGFR和白蛋白/肌酐比值）不相关。结论我们的数据表明，血液中特定链长的神经酰胺，很可能是血清中C24：1Cer的水平，可以作为SLE患者肾功能损害的有效生物标志物。1Cer血清水平不受糖皮质激素治疗的影响，并且与其他肾脏标志物（例如血清肌酐，eGFR和白蛋白/肌酐比值）不相关。结论我们的数据表明，血液中特定链长的神经酰胺，很可能是血清中C24：1Cer的水平，可以作为SLE患者肾功能损害的有效生物标志物。1Cer血清水平不受糖皮质激素治疗的影响，并且与其他肾脏标志物（例如血清肌酐，eGFR和白蛋白/肌酐比值）不相关。结论我们的数据表明，血液中特定链长的神经酰胺，很可能是血清中C24：1Cer的水平，可以作为SLE患者肾功能损害的有效生物标志物。