Lipid microarrays identify key mediators of autoimmune brain inflammation
Lipid microarrays identify key mediators of autoimmune brain inflammation
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DOI：
10.1038/nm1344
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发表时间：
2006-01-01
期刊：
影响因子：
82.9
通讯作者：
Robinson, WH
中科院分区：
文献类型：
--
作者：
Kanter, JL;Narayana, S;Robinson, WH
最近的研究表明，T细胞和自身抗体对脂质的反应性增加可能存在于自身免疫性脱髓鞘疾病多发性硬化症中。为了对多发性硬化症中的脂质抗体反应进行大规模的多重分析，我们开发了由髓鞘中存在的脂质组成的微阵列，所述脂质包括神经节苷脂、硫苷脂、神经鞘磷脂和总脑脂质组分。脂质阵列分析显示，来自多发性硬化症患者的脑脊液（CSF）中存在针对硫苷脂、鞘磷脂和氧化脂质的脂质特异性抗体。在急性实验性自身免疫性脑脊髓炎（EAE）的SJL/J小鼠中也检测到了硫酸酯特异性抗体。用硫苷脂加髓鞘肽免疫小鼠导致EAE的更严重的病程，并且施用硫苷脂特异性抗体加重EAE。因此，对硫苷脂和其他脂质的自身免疫反应存在于患有多发性硬化症和EAE的个体中，并且可能有助于自身免疫性脱髓鞘的发病机制。
Recent studies suggest that increased T-cell and autoantibody reactivity to lipids may be present in the autoimmune demyelinating disease multiple sclerosis. To perform large-scale multiplex analysis of antibody responses to lipids in multiple sclerosis, we developed microarrays composed of lipids present in the myelin sheath, including ganglioside, sulfatide, cerebroside, sphingomyelin and total brain lipid fractions. Lipid-array analysis showed lipid-specific antibodies against sulfatide, sphingomyelin and oxidized lipids in cerebrospinal fluid (CSF) derived from individuals with multiple sclerosis. Sulfatide-specific antibodies were also detected in SJL/J mice with acute experimental autoimmune encephalomyelitis (EAE). Immunization of mice with sulfatide plus myelin peptide resulted in a more severe disease course of EAE, and administration of sulfatide-specific antibody exacerbated EAE. Thus, autoimmune responses to sulfatide and other lipids are present in individuals with multiple sclerosis and in EAE, and may contribute to the pathogenesis of autoimmune demyelination.