Jean Pierre Aashika Raagavi, Kasirajan Anand, Green Siva Ranganathan, Sivaprakasam Manikandan, Sahaya Raj Rithanya Syam, Josyula Jhansi Venkata Nagamani, Mutheneni Srinivasa Rao, Subramanyam Veni, Pillai Agieshkumar Balakrishna
MGM Advanced Research Institute (MGMARI), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry 607402, India.
Department of General Medicine, Mahatma Gandhi Medical College and Research Institute (MGMCRI), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry 607 402, India.
Clin Chim Acta. 2025 Jun 15;574:120335. doi: 10.1016/j.cca.2025.120335. Epub 2025 Apr 28.
Sphingolipids are crucial for vascular integrity and cellular homeostasis, with recent studies highlighting their role in viral diseases.
The study aimed to assess the plasma levels of sphingolipids, specifically Sphingosine-1-phosphate (S1P) and the key enzymes of sphingolipid metabolism: Sphingomyelin synthase (SMS1), Ceramide Kinase (CERK) and acid ceramidase (ASAH1) and its association with clinical outcomes of dengue.
This prospective cohort study had 102 dengue cases with 17 severe dengue (SD), 33 dengue with warning signs (DWW), 52 dengue without warning signs (DWOW) along with 10 each from other febrile illnesses and healthy controls. Blood was collected across febrile, defervescence, and convalescence phases. Plasma levels of S1P and the enzymes were measured using ELISA, mRNA using qRT-PCR. Predictive efficacy was determined using Support vector machine (SVM) models.
Study showed a significant reduction in S1P levels across all dengue forms during febrile phases, with further decline in SD during the critical phase (P < 0.05).mRNA levels of the enzymes were increasing during critical phase (P ≤ 0.001) with no significant difference noted in their respective protein levels. S1P and SMS1 levels correlated significantly with clinical severity indicators, including hematocrit, albumin, platelet count, and liver enzymes. SVM analysis identified CERK levels along with platelet count, HCT, and ALT as markers with high predictive accuracy for dengue severity.
The study reports an association of sphingolipids with dengue virulence, emphasizing the role of S1P metabolism in disease progression and plasma leakage, and highlighting the potential of targeting sphingolipids in managing severe dengue.
鞘脂对血管完整性和细胞稳态至关重要，最近的研究突出了其在病毒性疾病中的作用。
本研究旨在评估鞘脂的血浆水平，特别是鞘氨醇-1-磷酸（S1P）以及鞘脂代谢的关键酶：鞘磷脂合酶（SMS1）、神经酰胺激酶（CERK）和酸性神经酰胺酶（ASAH1），并探讨其与登革热临床结局的关联。
这项前瞻性队列研究纳入了102例登革热病例，其中17例为重症登革热（SD），33例为有警告体征的登革热（DWW），52例为无警告体征的登革热（DWOW），另外还分别选取了10例其他发热性疾病患者和健康对照。在发热期、退热期和恢复期采集血液。采用酶联免疫吸附测定法（ELISA）检测血浆中S1P和酶的水平，采用定量逆转录聚合酶链反应（qRT-PCR）检测mRNA水平。使用支持向量机（SVM）模型确定预测效能。
研究表明，在发热期，所有登革热类型的S1P水平均显著降低，在重症登革热的关键期进一步下降（P < 0.05）。在关键期，这些酶的mRNA水平升高（P≤0.001），但其各自的蛋白质水平无显著差异。S1P和SMS1水平与临床严重程度指标显著相关，包括血细胞比容、白蛋白、血小板计数和肝酶。支持向量机分析确定CERK水平以及血小板计数、血细胞比容和丙氨酸转氨酶（ALT）是登革热严重程度预测准确性较高的标志物。
该研究报告了鞘脂与登革热病毒毒力的关联，强调了S1P代谢在疾病进展和血浆渗漏中的作用，并突出了靶向鞘脂治疗重症登革热的潜力。
