Alterations in Blood-Brain Barrier Permeability in Patients with Systemic Lupus Erythematosus
Alterations in Blood-Brain Barrier Permeability in Patients with Systemic Lupus Erythematosus
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DOI：
10.3174/ajnr.a5990
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发表时间：
2019-03-01
影响因子：
3.5
通讯作者：
Sanelli, P. C.
中科院分区：
文献类型：
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作者：
Chi, J. M.;Mackay, M.;Sanelli, P. C.
背景和目的：神经精神系统性红斑狼疮是指中枢和外周神经系统受累，其可能继发于抗神经元抗体穿过血脑屏障，优先靶向海马中的细胞，导致异常高代谢和萎缩。因此，我们假设BBB通透性的改变，动态对比增强MR成像检测，发生在海马系统性红斑狼疮患者神经精神系统性红斑狼疮的发展。材料和方法：6例无神经精神系统性红斑狼疮的系统性红斑狼疮患者和5名健康对照者进行了动态对比增强MR成像，并进行了BBB渗透性参数（K-transs和Ve）和CBF的后处理。标准化方法选择FDG-PET上检测到的异常脑区域的ROI采样。计算K-transs、Ve和CBF的平均值和SD。对K-transs和Ve与CBF进行线性回归和非参数斯皮尔曼等级相关分析。动态对比增强曲线和曲线下的面积为每个大脑区域。进行学生t检验比较。研究结果：定量数据显示，与对照组相比，系统性红斑狼疮患者的K-transs（P <0.001）和Ve（P <0.001）在统计学上增加。在系统性红斑狼疮患者中，K-transs（P <0.001）和Ve（P <0.001）与CBF呈显著正相关。此外，与对照组相比，系统性红斑狼疮患者的平均曲线下面积显示海马区的BBB通透性与其他脑区相比有统计学差异（P = 0.02）。结论：这些初步发现是概念验证，以支持系统性红斑狼疮患者的BBB通透性增加的假设，特别是在海马体，与其他大脑区域相比。这些发现可能会促进我们对自身免疫性疾病影响大脑的潜在病理生理学的理解。
BACKGROUND AND PURPOSE: Neuropsychiatric systemic lupus erythematosus refers to central and peripheral nervous system involvement, which may occur secondary to antineuronal antibodies crossing the blood-brain barrier that preferentially target cells in the hippocampus leading to abnormal hypermetabolism and atrophy. Thus, we hypothesized that alterations in BBB permeability, detected on dynamic contrast-enhanced MR imaging, occur in the hippocampus in patients with systemic lupus erythematosus before development of neuropsychiatric systemic lupus erythematosus. MATERIALS AND METHODS: Six patients with systemic lupus erythematosus without neuropsychiatric systemic lupus erythematosus and 5 healthy controls underwent dynamic contrast-enhanced MR imaging with postprocessing into BBB permeability parameters (K-trans and Ve) and CBF. Standardized methods selected ROI sampling of the abnormal brain regions detected on FDG-PET. The mean and SD of K-trans, Ve, and CBF were calculated. Linear regression and nonparametric Spearman rank correlation analyses of K-trans and Ve with CBF were performed. Dynamic contrast-enhanced curves and the area under the curve were generated for each brain region. Student t test comparisons were performed. RESULTS: Quantitative data revealed that patients with systemic lupus erythematosus have statistically increased K-trans (P < .001) and Ve (P < .001) compared with controls. In patients with systemic lupus erythematosus, statistically significant positive correlations were seen between K-trans (P < .001) and Ve (P < .001) with CBF. Furthermore, the mean area under the curve revealed statistically increased BBB permeability in the hippocampus (P = .02) compared with other brain regions in patients with systemic lupus erythematosus compared with controls. CONCLUSIONS: These initial findings are proof-of-concept to support the hypothesis that patients with systemic lupus erythematosus have increased BBB permeability, specifically in the hippocampus, compared with other brain regions. These findings may advance our understanding of the underlying pathophysiology affecting the brain in autoimmune diseases.