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A Haemophilus influenzae Strain Associated with Fisher Syndrome Expresses a Novel Disialylated Ganglioside Mimic
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文摘
The non-typeable Haemophilus influenzae strain DH1 was isolated from a 25 year old malepatient with Fisher syndrome, a postinfectious autoimmune condition characterized by the presence ofanti-GQ1b IgG antibodies that target and initiate damage to peripheral nerves. DH1 was found to displayan chars/alpha.gif" BORDER=0>NeuAc(2-8)chars/alpha.gif" BORDER=0>NeuAc(2-3)chars/beta2.gif" BORDER=0 ALIGN="middle">Gal branch bound to the tetraheptosyl backbone core of its lipooligosaccharide (LOS). The novel sialylation pattern was found to be dependent on the activity of a bifunctionalsialyltransferase, Lic3B, which catalyzes the addition of both the terminal and subterminal sialic acidresidues. Patient serum IgGs bind to DH1 LOS, and the reactivity is significantly influenced by the presenceof sialylated glycoforms. The display by DH1, of a surface glycan that mimics the terminal trisaccharideportion of disialosyl-containing gangliosides, provides strong evidence for its involvement in thedevelopment of Fisher syndrome.

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