Immunobiology of Stiff-Person Syndrome

Abstract

The two possibilities to explain the pathogenic basis of stiff-person syndrome (SPS) are intrathecal sensitization of GAD65-reactive CD4⁺T cells and synthesis of GAD65-specific autoantibodies within the CNS [Rakocevic et al., Arch. Neurol. 61: 902–904, 2004]; and peripheral antigen sensitization followed by CNS antigen recognition by autoantibodies that cross the blood-brain barrier. Antigen-specific CD4⁺ T cells are essential for the generation of high-affinity autoantibodies [Lanzavecchia, Nature 314: 537–539, 1985], but there is no evidence of cellular infiltration in the CNS of SPS patients [Warich-Kirches et al., Clin. Neuropathol. 16: 214–219, 1997; Ishizawa et al., Acta Neuropathol.(Berl) 97: 63–70, 1999]. This review discusses the possible role of autoantibodies and autoreactive T cells specific to neuronal antigens in SPS pathogenesis.

Keywords:

• autoimmunity
• gamma aminobutyric acid (GABA)
• glutamic acid decarboxylase autoantibodies
• stiff-person syndrome
• T cells