Document Detail


Neuronal surface glycolytic enzymes are autoantigen targets in post-streptococcal autoimmune CNS disease.
MedLine Citation:
PMID:  16356555     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Russell C Dale; Paul M Candler; Andrew J Church; Robin Wait; Jennifer M Pocock; Gavin Giovannoni
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-12-13
Journal Detail:
Title:  Journal of neuroimmunology     Volume:  172     ISSN:  0165-5728     ISO Abbreviation:  J. Neuroimmunol.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-02-28     Completed Date:  2006-05-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8109498     Medline TA:  J Neuroimmunol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  187-97     Citation Subset:  IM    
Affiliation:
Department of Neuroinflammmation, Institute of Neurology, University College London, and Neurosciences Unit, Great Ormond Street Hospital and Institute of Child Health, London WC1N 3JJ, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies / immunology*
Apoptosis / drug effects
Autoantigens / immunology*
Autoimmune Diseases / etiology,  immunology*
Blotting, Western / methods
Carrier Proteins / immunology
Case-Control Studies
Central Nervous System Diseases*
Chromatography / methods
Echocardiography / methods
Fructose-Bisphosphate Aldolase / immunology
Humans
Mass Spectrometry / methods
Membrane Proteins / immunology
Molecular Sequence Data
Molecular Weight
Phosphopyruvate Hydratase / immunology
RNA, Messenger / metabolism
Rats
Reverse Transcriptase Polymerase Chain Reaction / methods
Streptococcal Infections / complications,  immunology*
Thyroid Hormones / immunology
Chemical
Reg. No./Substance:
0/Antibodies; 0/Autoantigens; 0/Carrier Proteins; 0/Membrane Proteins; 0/RNA, Messenger; 0/Thyroid Hormones; 0/thyroid hormone-binding proteins; EC 4.1.2.13/Fructose-Bisphosphate Aldolase; EC 4.2.1.11/Phosphopyruvate Hydratase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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