Document Detail


Nucleic acid-associated autoantigens: pathogenic involvement and therapeutic potential.
MedLine Citation:
PMID:  20031372     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Autoimmunity to ubiquitously expressed macromolecular nucleic acid-protein complexes such as the nucleosome or the spliceosome is a characteristic feature of systemic autoimmune diseases. Disease-specificity and/or association with clinical features of some of these autoimmune responses suggest pathogenic involvement which, however, has been proven in only a few cases so far. Although the mechanisms leading to autoimmunity against nucleic acid-containing complexes are still far from being fully understood, there is increasing experimental evidence that the nucleic acid component may act as a co-stimulator or adjuvans via activation of nucleic acid-binding receptor systems such as Toll-like receptors in antigen-presenting cells. Dysregulated apoptosis and inappropriate stimulation of nucleic acid-sensing receptors may lead to loss of tolerance against the protein components of such complexes, activation of autoreactive T cells and formation of autoantibodies. This has been demonstrated to occur in systemic lupus erythematosus and seems to represent a general mechanism that may be crucial for the development of systemic autoimmune diseases. This review provides a comprehensive overview of the most thoroughly-characterized nucleic acid-associated autoantigens, describing their structure and biological function, as well as the nature and pathogenic importance of the reactivities directed against them. Furthermore, recent advances in immunotherapy such as antigen-specific approaches targeted at nucleic acid-binding antigens are discussed.
Authors:
Markus H Hoffmann; Sylvie Trembleau; Sylviane Muller; Günter Steiner
Publication Detail:
Type:  Journal Article; Review     Date:  2009-12-23
Journal Detail:
Title:  Journal of autoimmunity     Volume:  34     ISSN:  1095-9157     ISO Abbreviation:  J. Autoimmun.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-03-09     Completed Date:  2010-09-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8812164     Medline TA:  J Autoimmun     Country:  England    
Other Details:
Languages:  eng     Pagination:  J178-206     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Ltd. All rights reserved.
Affiliation:
Division of Rheumatology, Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
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MeSH Terms
Descriptor/Qualifier:
Animals
Autoantigens / immunology*,  therapeutic use
Autoimmune Diseases / immunology*,  therapy
Humans
Immunotherapy / trends
Nucleoproteins / immunology*,  therapeutic use
Nucleosomes / genetics,  immunology*,  metabolism
Spliceosomes / genetics,  immunology*,  metabolism
Chemical
Reg. No./Substance:
0/Autoantigens; 0/Nucleoproteins; 0/Nucleosomes

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