Cerebrospinal fluid lipocalin 2 in patients with clinically isolated syndromes and early multiple sclerosis
Cerebrospinal fluid lipocalin 2 in patients with clinically isolated syndromes and early multiple sclerosis
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DOI：
10.1177/1352458515624560
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发表时间：
2016-10-01
影响因子：
5.8
通讯作者：
Fazekas, F.
中科院分区：
文献类型：
--
作者：
Khalil, M.;Renner, A.;Fazekas, F.
背景：脂质运载蛋白2（LCN 2）可能参与多发性硬化（MS）的免疫发病机制，并可能进一步影响铁稳态。MS时脑铁蓄积;目的：探讨早期多发性硬化（MS）患者脑脊液（CSF）和血清LCN 2、转铁蛋白（Trf）和铁蛋白（Ferritin）与疾病进展和脑组织铁累积的关系。我们用酶联免疫吸附试验（ELISA）分析了55例患者的CSF和血清LCN 2，用散射比浊法分析了Trf和铁蛋白（45例临床孤立综合征（CIS），10例MS，中位临床随访4.8年）和63例对照。在患者中，我们通过3 T磁共振成像（MRI）R2* 弛豫测定法（中位成像随访2.2年）评估皮质下灰质铁。结果：与对照组相比，患者血清（p < 0.01）、CSF（p < 0.001）LCN 2和CSF Trf（p < 0.001）水平降低。CSF LCN 2与CSF Trf相关（r = 0.5，p < 0.001）。在临床稳定的患者中，CSF LCN 2水平与基底节铁积累相关（r = 0.5，p < 0.05）。在CIS中，更高的CSF LCN 2水平与转化为临床确诊的MS相关（p < 0.05）。结论：我们证明了在早期MS中改变的LCN 2调节，并提供了这可能与临床MS活动和基底神经节中铁积累相关的第一个证据。
Background: Lipocalin 2 (LCN2) may be involved in the immunopathogenesis of multiple sclerosis (MS) and might further impact on iron homoeostasis. Brain iron accumulates in MS; however, the association to iron-related proteins is still unsolved.Objective: To investigate cerebrospinal fluid (CSF) and serum LCN2, transferrin (Trf) and ferritin in early MS in relation to disease evolution and longitudinal brain iron accumulation.Methods: We analysed CSF and serum LCN2 by enzyme-linked immunosorbent assay (ELISA) and Trf and ferritin by nephelometry in 55 patients (45 clinically isolated syndrome (CIS), 10 MS, median clinical follow-up 4.8 years) and 63 controls. In patients, we assessed sub-cortical grey matter iron by 3T magnetic resonance imaging (MRI) R2* relaxometry (median imaging follow-up 2.2 years).Results: Compared to controls serum (p < 0.01), CSF (p < 0.001) LCN2 and CSF Trf (p < 0.001) levels were reduced in the patients. CSF LCN2 correlated with CSF Trf (r = 0.5, p < 0.001). In clinically stable patients, CSF LCN2 levels correlated with basal ganglia iron accumulation (r = 0.5, p < 0.05). In CIS, higher CSF LCN2 levels were associated with conversion to clinically definite MS (p < 0.05).Conclusion: We demonstrate altered LCN2 regulation in early MS and provide first evidence for this to be possibly linked to both clinical MS activity and iron accumulation in the basal ganglia.