Renal Division, Department of Medicine, Peking University First Hospital; Peking University Institute of Nephrology; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education; Peking-Tsinghua Center for Life Sciences, No.8, Xishiku Street, Xicheng District, Beijing, China.
Nephrol Dial Transplant. 2017 Aug 1;32(8):1313-1322. doi: 10.1093/ndt/gfw427.
C5a plays a crucial role in anti-neutrophil cytoplasmic antibody (ANCA)-mediated neutrophil recruitment and activation. Our previous studies found that the interaction between sphingosine-1-phosphate (S1P) and C5a plays an important role in the ANCA-mediated activation of neutrophils. In the current study, the expression levels of S1P in plasma and its receptors (S1PR1-5) in kidneys were analysed in patients with ANCA-associated vasculitis (AAV).
Plasma samples from 32 AAV patients in active stage and 20 AAV patients in remission were collected. The plasma levels of S1P were determined by an enzyme-linked immunosorbent assay (ELISA). The expression of S1PR1-5 in the renal specimens from 24 AAV patients was detected by immunohistochemistry. The associations of the plasma levels of S1P and renal expression of S1PRs with clinical and pathological parameters were analysed.
The level of plasma S1P was significantly higher in AAV patients in active stage than it was in both patients in remission and in normal controls. Correlation analysis showed that the plasma levels of S1P correlated with the initial serum creatinine levels (r = 0.502, P = 0.003) and inversely correlated with the estimated glomerular filtration rate (eGFR; r = -0.358, P = 0.044) in AAV patients. Double-labelling immunofluorescence assay suggested that S1PR1-5 were expressed on endothelial cells in the glomeruli and that S1PR1, 4 and 5 were expressed on neutrophils.
In AAV patients, the circulating S1P levels were elevated and the renal expression of S1PR2-5 was upregulated. The levels of circulating S1P and the renal expression of S1PR were associated with the renal involvement and disease activity of AAV.
C5a 在抗中性粒细胞胞浆抗体 (ANCA) 介导的中性粒细胞募集和激活中发挥关键作用。我们之前的研究发现，鞘氨醇-1-磷酸 (S1P) 与 C5a 之间的相互作用在 ANCA 介导的中性粒细胞激活中起着重要作用。在本研究中，分析了 ANCA 相关性血管炎 (AAV) 患者血浆中 S1P 的表达水平及其在肾脏中的受体 (S1PR1-5)。
收集 32 例活动期 AAV 患者和 20 例缓解期 AAV 患者的血浆样本。通过酶联免疫吸附试验 (ELISA) 测定 S1P 血浆水平。免疫组化检测 24 例 AAV 患者肾组织中 S1PR1-5 的表达。分析 S1P 血浆水平和 S1PRs 肾表达与临床和病理参数的相关性。
活动期 AAV 患者的 S1P 血浆水平明显高于缓解期患者和正常对照组。相关性分析显示，AAV 患者 S1P 血浆水平与初始血清肌酐水平呈正相关 (r = 0.502，P = 0.003)，与估算肾小球滤过率 (eGFR) 呈负相关 (r = -0.358，P = 0.044)。双标记免疫荧光染色提示 S1PR1-5 在肾小球内皮细胞表达，S1PR1、4 和 5 在中性粒细胞表达。
AAV 患者循环 S1P 水平升高，S1PR2-5 在肾脏表达上调。循环 S1P 水平和 S1PR 在肾脏的表达与 AAV 的肾脏受累和疾病活动度有关。
