Nucleic acid-associated autoantigens: pathogenic involvement and therapeutic potential.
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.
Hoffmann
Markus H
MH
Division of Rheumatology, Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Trembleau
Sylvie
S
Muller
Sylviane
S
Steiner
Günter
G
D000818:Animals; D001324:Autoantigens / Q000276:immunology* / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007167:Immunotherapy / Q000639:trends; D009698:Nucleoproteins / Q000276:immunology* / Q000627:therapeutic use; D009707:Nucleosomes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017381:Spliceosomes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D001324:Autoantigens; D009698:Nucleoproteins; D009707:Nucleosomes