1(st) Department of Neurology, National and Kapodistrian University of Athens, Eginition Hospital, Athens, Greece.
1(st) Department of Neurology, National and Kapodistrian University of Athens, Eginition Hospital, Athens, Greece.
Neurobiol Dis. 2022 Nov;174:105889. doi: 10.1016/j.nbd.2022.105889. Epub 2022 Oct 6.
Cholesterol is essential for myelin formation, but may also modulate mechanisms involved in adaptive immune responses. It is unclear whether lack of remyelination in multiple sclerosis (MS) results from an insufficient capacity of oligodendrocyte precursor cells to differentiate or from cholesterol insufficiency. Several studies have assessed the potential association of lipid profile and its metabolism with demyelination, disability, and disease progression. The aim of the present study was to measure cholesterol levels in plasma and cerebrospinal fluid (CSF) of patients with relapsing remitting MS (RRMS) or with clinically isolated syndrome (CIS), and to investigate whether there is an association between cholesterol levels and disease characteristics. Sixty-two patients with CIS and 46 patients with RRMS were included in the study. All patients had low EDSS and were medication-free at assessment. Forty-eight subjects within the same age range served as controls. Cholesterol concentrations were measured in plasma and in CSF by the same enzymatic - colorimetric method, and were related to clinical status, disease activity in magnetic resonance imaging (MRI) and presence of oligoclonal bands in CSF (OBs). Significantly lower levels of plasma and CSF cholesterol were found in patients compared to controls. Patients with OBs showed significantly lower levels of CSF cholesterol but not plasma cholesterol compared to OBs-negative patients. A positive correlation of plasma cholesterol with age and of CSF cholesterol with EDSS was found. Our results suggest that low CSF cholesterol in MS patients with positive OBs might reflect extensive demyelination and a more aggressive disease course associated with an increased humoral immune response against membrane components.
胆固醇对于髓鞘形成至关重要,但也可能调节适应性免疫反应的机制。多发性硬化症(MS)中髓鞘再生不足是由于少突胶质前体细胞分化能力不足还是由于胆固醇不足引起的尚不清楚。几项研究评估了脂质谱及其代谢与脱髓鞘、残疾和疾病进展的潜在关联。本研究旨在测量复发缓解型多发性硬化症(RRMS)或临床孤立综合征(CIS)患者血浆和脑脊液(CSF)中的胆固醇水平,并探讨胆固醇水平与疾病特征之间是否存在关联。本研究纳入了 62 例 CIS 患者和 46 例 RRMS 患者。所有患者在评估时 EDSS 较低且未接受药物治疗。48 名年龄相仿的受试者作为对照。采用相同的酶比色法测量血浆和 CSF 中的胆固醇浓度,并将其与临床状况、磁共振成像(MRI)中的疾病活动度和 CSF 中寡克隆带(OBs)的存在相关联。与对照组相比,患者的血浆和 CSF 胆固醇水平明显降低。与 OBs 阴性患者相比,OBs 阳性患者的 CSF 胆固醇水平明显降低,但血浆胆固醇水平无差异。发现血浆胆固醇与年龄呈正相关,CSF 胆固醇与 EDSS 呈正相关。我们的研究结果表明,OBs 阳性的 MS 患者 CSF 胆固醇水平较低可能反映了广泛的脱髓鞘和更具侵袭性的疾病过程,与针对膜成分的体液免疫反应增强有关。