Peripheral neuropathies and anti-glycolipid antibodies.

  • Willison H
  • Yuki N
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Abstract

This review charts the progress of anti-glycolipid antibodies in neuropathy, from their original discovery 20 years ago in immunoglobulin M paraproteinaemic neuropathy through to current discoveries mapping their relationship to subtypes of Guillain-Barré syndrome. Antibodies to >20 different glycolipids have now been associated with a wide range of clinically identifiable acute and chronic neuropathy syndromes. Particular progress has been achieved in understanding the link between acute motor axonal neuropathy and antibodies to GM1, GD1a, GM1b and GalNAc-GD1a, and between the cranial, bulbar and sensory variants of GBS and antibodies to the disialylated gangliosides GQ1b, GT1a, GD1b and GD3. In addition to clinical and serological studies, the origins and measurement of anti-glycolipid antibodies and their relationships to similar carbohydrate structures on infectious organisms, particularly Campylobacter jejuni, are discussed in the context of a molecular mimicry hypothesis. The structure and nomenclature of relevant glycolipids are outlined, along with information on their localization in nerve, and the influence this has on clinical phenotypes. Major advances have been made in animal modelling of anti-glycolipid antibody-associated diseases, both in vitro and in vivo. This has advanced our understanding of the role of anti-GQ1b antibodies in Miller Fisher syndrome with particular respect to the motor nerve terminal as a potential site of injury, and led to the creation of rabbit models of anti-GD1b and anti-GM1 antibody-mediated sensory and motor neuropathy, respectively. With such information in place, it will now be possible to determine the precise mechanisms by which antibodies injure the different compartments of peripheral nerve and establish how a range of immunomodulating therapies, including current treatments, exert their therapeutic effects. Despite these very significant advances, considerable gaps in our knowledge persist, and it is likely that other pathogenic pathways operate in inflammatory neuropathy that are unrelated to glycolipid antibodies, although these are outside the scope of this review.

Author-supplied keywords

  • Animals
  • Autoantibodies
  • Autoantibodies: biosynthesis
  • Autoantibodies: blood
  • Glycolipids
  • Glycolipids: blood
  • Glycolipids: immunology
  • Humans
  • Immunoglobulin G
  • Immunoglobulin G: biosynthesis
  • Immunoglobulin G: blood
  • Immunoglobulin M
  • Immunoglobulin M: biosynthesis
  • Immunoglobulin M: blood
  • Peripheral Nervous System Diseases
  • Peripheral Nervous System Diseases: blood
  • Peripheral Nervous System Diseases: immunology
  • Peripheral Nervous System Diseases: pathology

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Authors

  • Hugh J Willison

  • Nobuhiro Yuki

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