title: Nucleosomal DNA fragments in autoimmune diseases.
abstract: The inadequate response of immune cells to circulating apoptotic products, such as nucleosomal DNA fragments, is assumed to be a potent stimulus for the production of autoantibodies during the pathogenesis and progression of systemic lupus erythematosus (SLE). Here, we analyzed the levels of circulating nucleosomes, caspases, and C-reactive protein in sera of 244 individuals with various autoimmune diseases (155 with autoimmune hepatic disorders, 25 with ANCA-associated vasculitis, and 64 with various connective tissue diseases), and 32 healthy controls. Nucleosomes and caspase activities were significantly elevated in sera of patients with hepatic autoimmune diseases, connective tissue diseases, and particularly in ANCA-associated vasculitis when compared with healthy individuals. Nucleosomes showed a correlation with caspases, and caspases with C-reactive protein, but nucleosomes did not correlate with C-reactive protein. Serum levels of the apoptotic products, nucleosomes, and caspases are increased in various autoimmune diseases but may not be solely responsible for antinucleosome antibody production in SLE patients. It remains to be clarified whether qualitative changes in nucleosomes are linked with pathogenesis and disease progression in SLE.
authors.affiliation: Institute of Clinical Chemistry, University Hospital Munich-Grosshadern, Munich, Germany. Stefan.Holdenrieder@med.uni-muenchen.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Holdenrieder
authors.forename: Peter
authors.initials: P
authors.lastname: Eichhorn
authors.forename: Ulrich
authors.initials: U
authors.lastname: Beuers
authors.forename: Walter
authors.initials: W
authors.lastname: Samtleben
authors.forename: Ulf
authors.initials: U
authors.lastname: Schoenermarck
authors.forename: Reinhart
authors.initials: R
authors.lastname: Zachoval
authors.forename: Dorothea
authors.initials: D
authors.lastname: Nagel
authors.forename: Petra
authors.initials: P
authors.lastname: Stieber
mesh_terms: D017209:Apoptosis / Q000502:physiology; D001327:Autoimmune Diseases / Q000235:genetics*; D002097:C-Reactive Protein / Q000378:metabolism; D020169:Caspases / Q000097:blood; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053938:DNA Fragmentation; D006801:Humans; D009707:Nucleosomes / Q000235:genetics* / Q000378:metabolism; D013223:Statistics as Topic
chemical_list: D009707:Nucleosomes; D002097:C-Reactive Protein; D004247:DNA; D020169:Caspases