Published online: 11 December 2005; | doi:10.1038/nm1344
Lipid microarrays identify key mediators of autoimmune brain inflammation
Jennifer L Kanter1, 2, Sirisha Narayana2, Peggy P Ho2, Ingrid Catz3, Kenneth G Warren3, Raymond A Sobel4, 6, Lawrence Steinman2 & William H Robinson5, 6
Correspondence should be addressed to William H Robinson wrobins@stanford.edu
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.
脂质微阵技术可确认自身免疫病脑组织炎症中的关键介质
近期研究发现，自身免疫性脱髓鞘疾病多发性硬化T细胞和抗脂质的自身抗体反应性升高。我们采用微列阵技术对多发性硬化脂质反应性抗体进行大规模多重分析，微列阵组成包括髓鞘中的脂质，其中包括神经节苷脂、脑硫脂、脑苷脂、鞘磷脂、总的脑脂质。脂质列阵分析发现多发性硬化病人脑脊液中存在抗脑硫脂、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)SJL/J小鼠也可检出脑硫脂特异性抗体。小鼠经脑硫脂和髓鞘肽免疫处理后可致更重的EAE病程，给予脑硫脂特异性抗体加重EAE损害。因此，多发性硬化和EAE病人可见针对脑硫脂和其他脂类的自身免疫性反应，这种免疫反应可致自身免疫性脱髓鞘的发病机制。
