Department of General Pharmacology and Toxicology, Goethe University Hospital and Goethe University Frankfurt, Frankfurt am Main, Germany; Department of Nephrology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany.
Department of Nephrology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany.
Prostaglandins Other Lipid Mediat. 2019 Oct;144:106348. doi: 10.1016/j.prostaglandins.2019.106348. Epub 2019 Jul 10.
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.
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 m 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 m 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.
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.
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.
狼疮肾炎（LN）是系统性红斑狼疮（SLE）最常见的器官表现，与预后不良有关。然而，尚未建立一种非侵入性但可靠的方法来诊断 LN。因此，我们评估了血液神经酰胺是否可以作为肾脏损伤的有效生物标志物。
在这项横断面研究中，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（肾小球滤过率（eGFR）均≥80 ml/min/1.73 m 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 m 和白蛋白/肌酐比>30 mg/g）确定。从所有参与者采集静脉血，并通过 LC-MS/MS 测量血浆和血清中的神经酰胺水平。
最有趣的是，与健康对照组和无肾损伤的 SLE 患者相比，在活检证实的 LN 患者和肾功能受损的患者的血浆和血清样本中，某些特定神经酰胺（Cer、C18Cer、C20Cer 和 C24:1Cer）的浓度升高。与 SLE 患者相比，C24:1dhCer 水平在 LN 患者的血浆和血清样本中升高。与健康对照组相比，LN 患者的神经鞘氨醇水平在血浆和血清中升高，但与 SLE 患者相比则没有升高。与健康对照组相比，LN 患者的神经鞘氨醇水平在血清样本中显著升高。与健康对照组和 SLE 患者相比，S1P 和 SA1P 水平在 SLE 和 LN 患者的血浆样本中升高。对 LN 患者与 SLE 患者之间最改变的神经酰胺种类（C16Cer、C18Cer、C20Cer、C24:1Cer）的血浆和血清数据进行后续 ROC 分析显示，具有显著 AUC 的高诊断区分度，尤其是 C24:1Cer 血清水平。此外，C24:1Cer 血清水平不受糖皮质激素治疗的影响，与其他肾脏标志物（如血清肌酐、eGFR 和白蛋白/肌酐比）无关。
我们的数据表明，血液中链长特异性神经酰胺，最有可能是 C24:1Cer 血清水平，可能作为 SLE 患者肾损伤的有效生物标志物。
