Plasma Lipidome Acts As Diagnostic Marker and Predictor for Cyclosporin Response in Patients with Aplastic Anemia

Abstract

Background：The lipid metabolomic profile has been well defined in the pathogenesis and differential diagnosis in patients with different myeloid diseases. However, the role of plasma lipidome was rarely explored, especially in aplastic anemia (AA), a disease which has close connection with lipid metabolism.Methods: Peripheral fasting serum levels of patients newly diagnosed with AA from March 2019 to December 2019 were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the serum lipid profiles. Meanwhile, the lipidomes for patients with hypocellular myelodysplastic syndrome (h-MDS) and age and sex matched healthy volunteers were taken as controls. The lipid profiles were tested again 6 months after standard cyclosporin A（CsA）treatment in patients with AA. For all the patients, those with a history of hyperlipidemia, diabetes, obesity (body mass index > 28 kg/m 2) or complications with other malignant diseases at diagnosis were excluded.Results: The study enrolled 15 patients with AA, 11 patients with h-MDS and 20 healthy controls. All the enrolled AA patients were non-severe and transfusion dependent, and were treated with CsA 3-5mg/kg/d for at least 6 months. For h-MDS patients, five were MDS with single lineage dysplasia, three were MDS with multilineage dysplasia, and three were MDS-Excess Blasts 1 (MDS-RAEB1). Metabolites in arachidonic acid pathway and retinol metabolism were significantly decreased in the AA patients compared with the healthy controls (P<0.05). AA patients had decreased arachidonic acid pathway metabolites and retinol metabolism-related metabolites as compared with h-MDS（P<0.05), whereas h-MDS patients had increased metabolism of proline and threonine and abnormal sphingolipid metabolism compared with AA patients and the normal controls. After 6-month of CsA treatment, leukotriene B4, 15(S)-HETE, all-trans-retinal and protectin D1 decreased significantly. Patients who had response to CsA had higher levels of baseline protectin D1 (p=0.011), leukotriene B4 (p=0.011), 15(S)-HETE (p=0.004) and all-trans-retinal (p=0.000) than those who had no response.Conclusion: The lipid profiles showed significant difference not only between patients with AA and healthy controls, but also between AA and h-MDS. Meanwhile, some of baseline value and the change in lipid molecules may predict the CsA response at 6 months. DisclosuresNo relevant conflicts of interest to declare.