RGD Reference Report - Neuronal surface glycolytic enzymes are autoantigen targets in post-streptococcal autoimmune CNS disease. - Rat Genome Database

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Neuronal surface glycolytic enzymes are autoantigen targets in post-streptococcal autoimmune CNS disease.

Authors: Dale, RC  Candler, PM  Church, AJ  Wait, R  Pocock, JM  Giovannoni, G 
Citation: Dale RC, etal., J Neuroimmunol. 2006 Mar;172(1-2):187-97. Epub 2005 Dec 13.
RGD ID: 2301134
Pubmed: PMID:16356555   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jneuroim.2005.10.014   (Journal Full-text)

Infection with the Group A Streptococcus (GAS) can result in immune mediated brain disease characterised by a spectrum of movement and psychiatric disorders. We have previously described anti-neuronal antibodies in patients that bind to a restricted group of brain antigens with molecular weights 40 kDa, 45 kDa (doublet) and 60 kDa. The aim of this study was to define these antigens using 2-dimensional electrophoresis or ion exchange and hydrophobic interaction chromatography, followed by mass spectrometry. The findings were confirmed using commercial antibodies, commercial antigens and recombinant human antigens. The autoantigens were neuronal glycolytic enzymes--NGE (pyruvate kinase M1, aldolase C, neuronal-specific and non-neuronal enolase). These are multifunctional proteins that are all expressed intracellularly and on the neuronal cell surface. On the neuronal plasma membrane, NGE are involved in energy metabolism, cell signalling and synaptic neurotransmission. Anti-NGE antibodies were more common in the 20 unselected post-streptococcal CNS patients compared to 20 controls. In vitro experiments using cultured neurons showed that commercial anti-NGE antibodies induced apoptosis compared to blank incubation and control anti-HuD antibody. GAS also expresses glycolytic enzymes on cell surfaces that have 0-49% identity with human NGE, suggesting molecular mimicry and autoimmune cross-reactivity may be the pathogenic mechanism in post-streptococcal CNS disease.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ALDOCHumanautoimmune disease of the nervous system  IDA associated with Streptococcal InfectionsRGD 
AldocRatautoimmune disease of the nervous system  ISOALDOC (Homo sapiens)associated with Streptococcal InfectionsRGD 
AldocMouseautoimmune disease of the nervous system  ISOALDOC (Homo sapiens)associated with Streptococcal InfectionsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Aldoc  (aldolase, fructose-bisphosphate C)

Genes (Mus musculus)
Aldoc  (aldolase C, fructose-bisphosphate)

Genes (Homo sapiens)
ALDOC  (aldolase, fructose-bisphosphate C)


Additional Information