Passive immunization with anti-ganglioside antibodies directly inhibits axon regeneration in an animal model

Helmar C. Lehmann, Pablo Lopez, Gang Zhang, Thien Ngyuen, Jiangyang Zhang, Bernd C. Kieseier, Susumu Mori, Kazim A. Sheikh

Research output: Contribution to journalArticle

Abstract

Recent studies have proposed that neurite outgrowth is influenced by specific nerve cell surface gangliosides, which are sialic acid-containing glycosphingolipids highly enriched in the mammalian nervous system. For example, the endogenous lectin, myelin-associated glycoprotein (MAG), is reported to bind to axonal gangliosides (GD1a and GT1b) to inhibit neurite outgrowth. Clustering of gangliosides in the absence of inhibitors such as MAG is also shown to inhibit neurite outgrowth in culture. In some human autoimmune PNS and CNS disorders, autoantibodies against GD1a or other gangliosides are implicated in pathophysiology. Because of neurobiological and clinical relevance, we asked whether anti-GD1a antibodies inhibit regeneration of injured axons in vivo. Passive transfer of anti-GD1a antibody severely inhibited axon regeneration after PNS injury in mice. In mutant mice with altered ganglioside or complement expression, inhibition by antibodies was mediated directly through GD1a and was independent of complement-induced cytolytic injury. The impaired regenerative responses and ultrastructure of injured peripheral axons mimicked the abortive regeneration typically seen after CNS injury. These data demonstrate that inhibition of axon regeneration is induced directly by engaging cell surface gangliosides in vivo and imply that circulating autoimmune antibodies can inhibit axon regeneration through neuronal gangliosides independent of endogenous regeneration inhibitors such as MAG.

Original languageEnglish (US)
Pages (from-to)27-34
Number of pages8
JournalJournal of Neuroscience
Volume27
Issue number1
DOIs
StatePublished - Jan 3 2007

Fingerprint

Passive Immunization
Gangliosides
Axons
Regeneration
Anti-Idiotypic Antibodies
Animal Models
Myelin-Associated Glycoprotein
Wounds and Injuries
Glycosphingolipids
Antibodies
N-Acetylneuraminic Acid
Lectins
Autoantibodies
Nervous System
Cluster Analysis
Neurons
Neuronal Outgrowth

Keywords

  • Animal model
  • Anti-ganglioside antibodies
  • Axon regeneration
  • Gangliosides
  • Guillain-Barré syndrome
  • Passive transfer

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Passive immunization with anti-ganglioside antibodies directly inhibits axon regeneration in an animal model. / Lehmann, Helmar C.; Lopez, Pablo; Zhang, Gang; Ngyuen, Thien; Zhang, Jiangyang; Kieseier, Bernd C.; Mori, Susumu; Sheikh, Kazim A.

In: Journal of Neuroscience, Vol. 27, No. 1, 03.01.2007, p. 27-34.

Research output: Contribution to journalArticle

Lehmann, Helmar C. ; Lopez, Pablo ; Zhang, Gang ; Ngyuen, Thien ; Zhang, Jiangyang ; Kieseier, Bernd C. ; Mori, Susumu ; Sheikh, Kazim A. / Passive immunization with anti-ganglioside antibodies directly inhibits axon regeneration in an animal model. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 1. pp. 27-34.
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