The role of glycosphinglipids in neurological disorders - Mechanisms of immune action

Robert K. Yu, Toshio Ariga

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Specific criteria that are required for understanding the significance of glycosphingolipid (GSL) antibodies, as well as mechanisms that may underlie the immunopathogenesis of these disorders, are proposed. These criteria are illustrated by describing the role of a unique family of acidic GSLs, the sulfated glucuronosyl glycolipids (SGGLs), in the pathogenic mechanisms of peripheral neuropathy with IgM paraproteinemia. High anti-SGGL antibody titers are detected in patients suffering from this disorder. It is demonstrated that SGGLs, which possess a common carbohydrate epitope with myelin-associated glycoprotein (MAG), several low-molecular-weight glycoproteins in the PNS, and a number of cell adhesion molecules, are potential target antigens for the neuropathy. Evidence is provided that sensitization of laboratory animals with pure SGGLs elicits experimental peripheral neuropathies that exhibit remarkable similarities with respect to antibody specificity, and electrophysiological and pathological features to the human conditions. By intraneural injection of antibodies into the sciatic nerve of rats, it is demonstrated that pathological changes consisting of demyelination and axonal degeneration are mediated by an antibody- and complement-dependent process. To elucidate the mechanisms of antibody penetration from circulation into the endoneurial space, it is further shown that brain microvascular endothelial cells express SGGLs. Moreover it has been found that inflammatory cytokines are capable of upregulating the expression of SGGLs on the endothelial cell surface, resulting in a greater attachment of leukocytes. This latter observation suggests that SGGLs may also participate in cell-mediated responses in certain inflammatory neurological disorders.

Original languageEnglish (US)
Pages (from-to)285-306
Number of pages22
JournalAnnals of the New York Academy of Sciences
Volume845
DOIs
StatePublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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