Stiff-person syndrome (SPS) and anti-GAD-related CNS degenerations: Protean additions to the autoimmune central neuropathies

Fatima Ali, Merrill Rowley, Bindu Jayakrishnan, Suzanne Teuber, M Eric Gershwin, Ian Mackay

Research output: Contribution to journalReview ArticleResearchpeer-review

58 Citations (Scopus)

Abstract

Stiff Person Syndrome (SPS) is a rare autoimmune neurological disease attributable to autoantibodies to glutamic acid decarboxylase (anti-GAD) more usually associated with the islet beta cell destruction of autoimmune type 1 diabetes (T1D). SPS is characterized by interference in neurons with the synthesis/activity of the inhibitory neurotransmitter gamma amino butyric acid (GABA) resulting in the prototypic progressive spasmodic muscular rigidity of SPS, or diverse neurological syndromes, cerebellar ataxia, intractable epilepsy, myoclonus and several others. Remarkably, a single autoantibody, anti-GAD, can be common to widely different disease expressions, i.e. T1D and SPS. One explanation for these data is the differences in epitope engagement between the anti-GAD reactivity in SPS and T1D: in both diseases, anti-GAD antibody reactivity is predominantly to a conformational epitope region in the PLP- and C-terminal domains of the 65 kDa isoform but, additionally in SPS, there is reactivity to conformational epitope(s) on GAD67, and short linear epitopes in the C-terminal region and at the N-terminus of GAD65. Another explanation for disease expressions in SPS includes ready access of anti-GAD to antigen sites due to immune responsiveness within the CNS itself according to intrathecal anti-GAD-specific B cells and autoantibody. Closer study of the mysterious stiff-person syndrome should enhance the understanding of this disease itself, and autoimmunity in general. © 2011 Elsevier Ltd.

Original languageEnglish
Pages (from-to)79 - 87
Number of pages9
JournalJournal of Autoimmunity
Volume37
Issue number2
DOIs
Publication statusPublished - Sep 2011

Keywords

  • Anti-amphiphysin antibodies
  • Anti-GABAA receptor-associated protein antibody
  • Anti-GAD 65/67 antibodies
  • Autoimmunity
  • GABA neurotransmission
  • Glutamic acid decarboxylase (GAD) isoforms
  • Stiff-person syndrome

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