Nucleic acid-associated autoantigens: pathogenic involvement and therapeutic potential.

Abstract

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
• Journal: Journal of autoimmunity (J Autoimmun) Vol. 34 Issue 3 Pg. J178-206 (May 2010) ISSN: 1095-9157 [Electronic] England
• PMID: 20031372 (Publication Type: Journal Article, Review)
• Copyright: Copyright 2009 Elsevier Ltd. All rights reserved.

Chemical References

• Autoantigens
• Nucleoproteins
• Nucleosomes

Topics

• Animals
• Autoantigens (immunology, therapeutic use)
• Autoimmune Diseases (immunology, therapy)
• Humans
• Immunotherapy (trends)
• Nucleoproteins (immunology, therapeutic use)
• Nucleosomes (genetics, immunology, metabolism)
• Spliceosomes (genetics, immunology, metabolism)