18:2 Cholesterol Ester is a Novel Prognostic Biomarker of Disease Progression in Multiple Sclerosis

Multiple sclerosis (MS) presents diverse clinical outcomes. Cholesterol esterification (CE) has been implicated as a disease mechanism involved in the remyelination process. We investigated whether cerebrospinal fluid (CSF) 18:2 cholesterol ester (18:2 CE) levels at diagnosis could predict 10-year MS progression. We aimed to determine if CSF 18:2 CE levels correlate with long-term disease progression. In a retrospective case-control single-centre study with 115 MS patients and 57 controls, we conducted targeted lipidomic analysis of CSF. Clinical data, oligoclonal bands, brain and spinal cord MRI, and CSF 18:2 CE levels were collected. Elevated CSF 18:2 CE levels were significantly associated with a higher risk of 10-year MS progression, with an AUC of 0.91 in a multivariable logistic regression model. Patients initially treated with a high-efficacy drug did not show a worse prognosis despite presenting elevated CE18:2 levels at the time of diagnosis. However, patients treated with a high-efficacy drug as a second or third option showed a positive correlation between CE18:2 levels and EDSS at 10 years. CSF 18:2 CE is a potential prognostic biomarker for predicting long-term MS progression, potentially indicating reduced remyelination capacity. These findings hold promise for improved patient management and warrant prospective validation.