Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea

Speaker: 萬書文

Commentator:余俊強 老師

Time: 13:00-14:00 10/08/2003

Place: Room 601

Abstract

Acute rheumatic fever (ARF) is an autoimmune sequela of group A streptococcal (GAS) infection, and Sydenham chorea (SC) is the principal neurologic manifestation of ARF. Sydenham chorea is characterized by involuntary movements, muscle weakness and emotional disturbances¹. The monoclonal antibodies derived from a Sydenham chorea patient showed specificity for mammalian lysoganglioside and the group A streptococcal carbohydrate, N-acetyl-b-D-glucosamine (GlcNAc). Sydenham chorea antibodies reacted with human neuronal cells and basal ganglia. Thus, molecular mimicry was implicated in this disorder through the demonstration of antineuronal antibodies in sera from patients with Sydenham chorea². Antibody-mediated activation of calcium/calmodulin-dependent protein (CaM) kinase II was analyzed to determine whether signal transduction is involved in the mechanism of  immunopathogensis³. The ability of antineuronal antibodies to activate CaM kinase II was similar to acute Sydenham chorea sera and CSF. In contrast, convalescent Sydenham chorea sera and sera from patients with ARF in the absence of chorea could not induce significant CaM kinase II activity. This study revealed cross-reactivity between GAS and neuronal tissue, which may produce central nervous system (CNS) dysfunction through autoantibody-mediated signal transducation by CaM kinase II.

References:

1. Cunningham, M. W. (2000). Pathogenesis of group A streptococcal infections. Clinical Microbiology Reviews 13, 472-511.

2. Snider, L. A., et al. (2003). Post-streptococcal autoimmune disorders of the central nervous system. Current Opinion in Neurology 16, 359-365.

3. Kirvan, C. A., et al. (2003). Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea. Nature Medicine 9, 914-920.