Lipid microarrays identify key mediators of autoimmune brain inflammation.
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.
Kanter
Jennifer L
JL
Department of Microbiology and Immunology, Stanford University School of Medicine, 279 Campus Drive, Stanford, California 94305, USA.
Narayana
Sirisha
S
Ho
Peggy P
PP
Catz
Ingrid
I
Warren
Kenneth G
KG
Sobel
Raymond A
RA
Steinman
Lawrence
L
Robinson
William H
WH
D000818:Animals; D001327:Autoimmune Diseases / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000473:pathology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000134:cerebrospinal fluid / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D046228:Microarray Analysis / Q000295:instrumentation / Q000379:methods*; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013433:Sulfoglycosphingolipids / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism
D008055:Lipids; D013433:Sulfoglycosphingolipids