Protective associations of HDL with blood-brain barrier injury in multiple sclerosis patients
Protective associations of HDL with blood-brain barrier injury in multiple sclerosis patients
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DOI：
10.1194/jlr.m060970
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发表时间：
2015-10-01
影响因子：
6.5
通讯作者：
Ramanathan, Murali
中科院分区：
文献类型：
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作者：
Fellows, Kelly;Uher, Tomas;Ramanathan, Murali
这项工作的目的是研究血清胆固醇和载脂蛋白与血脑屏障（BBB）通透性和CNS炎症的措施后，第一次临床脱髓鞘事件的关联。该研究包括154名患者[67%为女性;年龄为29.5 ± 8.2岁（平均值± SD）]，这些患者在首次脱髓鞘事件后参加了干扰素1-a治疗的多中心研究。治疗前筛选时采集血液和脑脊液（CSF）。获得了全面的血脂谱和BBB破坏和CNS免疫活性的多种替代标志物。血清HDL胆固醇（HDL-C）和ApoA-I水平升高与CSF总蛋白水平、CSF白蛋白水平、白蛋白商和CSF IgG水平降低相关（HDL-C均P <0.001，ApoA-I均P < 0.01）。HDL-C还与CSF CD 80+（P < 0.001）和CSF CD 80 + CD 19+（P = 0.007）细胞频率相关。较高的血清HDL与较低水平的BBB损伤和减少的CD 80+和CD 80 + CD 19+细胞外渗到CSF中相关。HDL可能潜在地抑制第一次脱髓鞘事件后致病性BBB损伤的起始和/或维持。
The purpose of this work was to investigate the associations of serum cholesterol and apolipoproteins with measures of blood-brain barrier (BBB) permeability and CNS inflammation following the first clinical demyelinating event. This study included 154 patients [67% female; age, 29.5 +/- 8.2 years (mean +/- SD)] enrolled in a multi-center study of interferon 1-a treatment following the first demyelinating event. Blood and cerebrospinal fluid (CSF) were obtained at screening prior to treatment. A comprehensive serum lipid profile and multiple surrogate markers of BBB breakdown and CNS immune activity were obtained. Higher levels of serum HDL cholesterol (HDL-C) and ApoA-I were associated with lower CSF total protein level, CSF albumin level, albumin quotient, and CSF IgG level (all P 0.001 for HDL-C and all P < 0.01 for ApoA-I). HDL-C was also associated with CSF CD80+ (P < 0.001) and with CSF CD80+CD19+ (P = 0.007) cell frequencies. Higher serum HDL is associated with lower levels of BBB injury and decreased CD80+ and CD80+CD19+ cell extravasation into the CSF. HDL may potentially inhibit the initiation and/or maintenance of pathogenic BBB injury following the first demyelinating event.