Abstract
Neuromyelitis optica spectrum disorder (NMOSD) is a neuroinflammatory disease caused by aquaporin-4 IgG antibodies, which damage astrocytes and trigger inflammation. Although altered lipid profiles have been observed in various neuroinflammatory diseases, the role of dyslipidemia in NMOSD disease activity remains poorly understood. In this study, we analyzed plasma lipoprotein profiles in 40 patients with NMOSD during relapses, 35 patients with multiple sclerosis (MS) during relapses, and 41 age- and sex-matched healthy controls (HCs). Among 112 lipoprotein components, 39 showed significant alterations in NMOSD patients compared with both MS patients and HCs. These components exhibited consistently lower levels during relapses. Receiver operating characteristic analysis identified total apolipoprotein-A2 (Apo-A2; area under the curve [AUC] = 0.808), HDL-3-Apo-A2 (AUC = 0.806), HDL-Apo-A2 (AUC = 0.798), VLDL-2-phospholipids (PLs; AUC = 0.774), VLDL-3-PLs (AUC = 0.769), and VLDL-3-triglycerides (AUC = 0.770) as robust biomarkers for distinguishing NMOSD from HCs, whereas VLDL-3-PLs (AUC = 0.791) and HDL-3-Apo-A2 (AUC = 0.752) effectively differentiated NMOSD from MS. Importantly, HDL-4-Apo-A2 levels negatively correlated with Expanded Disability Status Scale scores (r = -0.321, P = 0.043) and spinal cord lesion length (r = -0.391, P = 0.013) in NMOSD patients. Among 22 NMOSD patients evaluated longitudinally, 36 of the 39 dysregulated lipoprotein components return to normal levels during remission. This study represents the first comprehensive lipidomic analysis in NMOSD, revealing distinct dyslipidemia patterns associated with disease activity and highlighting the potential of lipoprotein profiling as a noninvasive prognostic biomarker.