Anti-glycolipid antibodies in guillain-barré syndrome and related neuropathies: Therapeutic strategies for disease treatment

Robert K Yu, Seigo Usuki, Toshio Ariga

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations

Abstract

Guillain-Barré syndrome (GBS) and its variants are autoimmune neuropathies that frequently occur as a result of enteritis resulting from an infectious event caused by bacterial pathogens such as Campylobacter jejuni. These neuropathies are classified as several disorders characterized by an immune-mediated attack on the peripheral nervous system, particularly on the myelin sheath and axon of sensory and motor nerves. Increased antibody titers in GBS and its variants are thought to be caused by production of antibodies to C. jejuni-containing carbohydrate antigen(s) that also show cross-reactivity with gangliosides of the myelin sheath and the axons of peripheral nerve cells. For this reason, the most common diagnostic test of GBS is to detect circulating anti-glycolipid antibodies in patients thought to have GBS. Pathogenesis of GBS is believed to involve a molecular mimicry mechanism between epitopes on bacterial (e.g., C. jejuni) lipo-oligosaccharides (LOSs) and peripheral nerve glycolipids, particularly gangliosides, resulting in demyelination and/or axonal degeneration. It has been reported that sera of 60% of patients with GBS contain one or more anti-ganglioside antibodies. Other glycolipid antigens include sulfatides and sulfated glucuronosyl glycolipids (SGGLs). These antibodies contribute to the pathogenesis of GBS, and their presence represents an important diagnostic marker for GBS. Recently it has been shown that these antibodies are often concealed in certain patients' sera that are anti-ganglioside antibody negative but they react with a mixed form of gangliosides (e.g., GD1a and GD1b), and not with individual purified ganglioside alone. This novel class of autoantibodies has been termed anti-ganglioside-complex (GSC) antibodies. These anti-GSC antibodies also are involved in the pathogenesis of GBS and its variants. Antibody- and/or cell-mediated immune responses are believed to induce pathological lesions of the nerve, resulting in loss of conduction velocity or conduction block. Recent studies also revealed that interruption of neurotransmission could occur as a result of interaction of anti-ganglioside antibodies with ion channels at the nodes of Ranvier. Accumulating ex vivo electrophysiological evidence suggests that ganglioside molecular mimicry may be responsible for muscle weakness, possibly via the action of anti-ganglioside antibodies on cell-surface ganglioside antigens of the neuromuscular junction. Although plasmapheresis and intravenous immunoglobulin (IVIG) are commonly used for the treatment of patients with GBS, we have recently developed novel and effective therapeutic strategies employing glycomimics such as anti-idiotypic antibodies and phage-displayed peptides to target specific pathogenic antibodies for elimination in an animal model of GBS. These treatment strategies should represent a novel approach for treatment of GBS and related autoimmune disorders.

Original languageEnglish (US)
Title of host publicationAnticarbohydrate Antibodies
Subtitle of host publicationFrom Molecular Basis to Clinical Application
PublisherSpringer-Verlag Wien
Pages327-359
Number of pages33
Volume9783709108703
ISBN (Electronic)9783709108703
ISBN (Print)3709108691, 9783709108697
DOIs
StatePublished - Oct 1 2012

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology and Microbiology(all)

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    Yu, R. K., Usuki, S., & Ariga, T. (2012). Anti-glycolipid antibodies in guillain-barré syndrome and related neuropathies: Therapeutic strategies for disease treatment. In Anticarbohydrate Antibodies: From Molecular Basis to Clinical Application (Vol. 9783709108703, pp. 327-359). Springer-Verlag Wien. https://doi.org/10.1007/978-3-7091-0870-3_14