Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea.
Streptococcus pyogenes-induced acute rheumatic fever (ARF) is one of the best examples of postinfectious autoimmunity due to molecular mimicry between host and pathogen. Sydenham chorea is the major neurological manifestation of ARF but its pathogenesis has remained elusive, with no candidate autoantigen or mechanism of pathogenesis described. Chorea monoclonal antibodies showed specificity for mammalian lysoganglioside and N-acetyl-beta-D-glucosamine (GlcNAc), the dominant epitope of the group A streptococcal (GAS) carbohydrate. Chorea antibodies targeted the surface of human neuronal cells, with specific induction of calcium/calmodulin-dependent protein (CaM) kinase II activity by monoclonal antibody 24.3.1 and sera from active chorea. Convalescent sera and sera from other streptococcal diseases in the absence of chorea did not activate the kinase. The new evidence implicates antibody-mediated neuronal cell signaling in the immunopathogenesis of Sydenham chorea and will lead to a better understanding of other antibody-mediated neurological disorders.
Kirvan
Christine A
CA
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Swedo
Susan E
SE
Heuser
Janet S
JS
Cunningham
Madeleine W
MW
D000117:Acetylglucosamine / Q000276:immunology; D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism*; D001921:Brain / Q000276:immunology / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D002819:Chorea / Q000276:immunology* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005677:G(M1) Ganglioside / Q000031:analogs & derivatives* / Q000276:immunology; D006801:Humans; D007106:Immune Sera; D018716:Molecular Mimicry; D009474:Neurons / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D013291:Streptococcus / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007106:Immune Sera; C029465:lysoGM1 ganglioside; D005677:G(M1) Ganglioside; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000117:Acetylglucosamine