Qin J, Goswami R, Balabanov R, Dawson G
Department of Pediatrics, University of Chicago, Chicago, Illinois, USA.
J Neurosci Res. 2007 Apr;85(5):977-84. doi: 10.1002/jnr.21206.
Multiple sclerosis (MS) is a common autoimmune neurodegenerative disease of unknown cause, which results in inflammation and plaques of demyelination in brain and eventual axonal degeneration. We report the novel presence of oxidized phosphatidylcholine [1-palmitoyl-2-(5'-oxo)valeryl-sn-glycero-3-phosphorylcholine (POVPC)], a lipid associated with inflammatory diseases such as atherosclerosis and lung disease, in the brain of MS patients. The OxPC epitope was detected by Western blotting with the E06 monoclonal antibody. E06-positive lipid was present in the highest amounts in MS plaques, which also showed evidence of low-molecular-weight (15-kDa) OxPC-modified protein. E06 reactivity did not change with post-mortem interval, and E06-positive lipids were largely absent from control tissue. We then used a second monoclonal antibody (AB1-2, which recognizes the E06/T15 idiotype and therefore detects the presence of antibody to OxPC) to show that MS brain samples were strongly positive for the 50-kDa antibody heavy chain. We also showed that isoelectric focussing of the oligoclonal IgG characteristic of MS revealed some immunoglobulin bands that Western blotted with the AB1-2 antibody. Spinal cords from mice induced to undergo experimental allergic encephalomyelitis (EAE) also showed strong AB1-2 reactivity by both immunocytochemistry and Western blot analysis. We therefore conclude that we can detect both OxPC and 15-kDa protein modified by OxPC and the antibody to the antibody to OxPC (antiidiotype) in pathological tissue and suggest that this could play a role in the progression of MS.
多发性硬化症(MS)是一种病因不明的常见自身免疫性神经退行性疾病,可导致脑部炎症和脱髓鞘斑块,最终引起轴突变性。我们报告了在MS患者大脑中发现了氧化磷脂酰胆碱[1-棕榈酰-2-(5'-氧代)戊酰基-sn-甘油-3-磷酸胆碱(POVPC)],这种脂质与动脉粥样硬化和肺部疾病等炎症性疾病有关。通过使用E06单克隆抗体进行蛋白质印迹法检测到了氧化磷脂酰胆碱(OxPC)表位。E06阳性脂质在MS斑块中含量最高,同时也显示出低分子量(15 kDa)OxPC修饰蛋白的证据。E06反应性不会随死后间隔时间而改变,并且对照组织中基本不存在E06阳性脂质。然后,我们使用了第二种单克隆抗体(AB1-2,它识别E06/T15独特型,因此可检测到抗OxPC抗体的存在)来表明MS脑样本对50 kDa抗体重链呈强阳性。我们还表明,MS特征性寡克隆IgG的等电聚焦显示出一些免疫球蛋白条带,这些条带与AB1-2抗体进行蛋白质印迹反应。通过免疫细胞化学和蛋白质印迹分析,诱导发生实验性自身免疫性脑脊髓炎(EAE)的小鼠脊髓也显示出强烈的AB1-2反应性。因此,我们得出结论,我们可以在病理组织中检测到OxPC以及被OxPC修饰的15 kDa蛋白和抗OxPC抗体的抗体(抗独特型),并表明这可能在MS的进展中起作用。