title: Decreased serum DNase1-activity in patients with autoimmune liver diseases.
abstract: Deoxyribonuclease1 (DNase1) is involved in chromatin degradation of apoptotic cells. Its deficiency results in accumulation of self-DNA, which in turn may induce inflammation and autoimmunity. We assessed for the first time serum DNase1-activity in a large consecutive cohort of treatment-naïve patients with autoimmune liver diseases (ALD). DNase1-activity was determined by single radial enzyme-diffusion (SRED) at diagnosis of 224 patients with autoimmune hepatitis (AIH), 249 with primary biliary cirrhosis (PBC) and 36 with primary sclerosing cholangitis (PSC). Sera from 146 patients with chronic hepatitis B or C, 140 with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) and 114 healthy individuals served as disease and healthy controls. Available serum samples during remission from 50 AIH and 39 PBC patients were also investigated by paired analyzes. DNase1-activity was significantly lower in AIH, PBC and PSC compared to viral hepatitis (p < 0.02, p < 0.001, p = 0.03), NAFLD/NASH (p < 0.001) and healthy (p < 0.001). No significant difference was found in between each specific ALD. In AIH, DNAse1-activity was positively correlated with aspartate aminotransferase (AST) (p < 0.02), bilirubin (p < 0.01) and increased IgG (>1400 mg/dl; p < 0.05); in PBC, with AST (p < 0.01), alanine aminotransferase (ALT) (p < 0.03) and anti-mitochondrial antibodies (AMA) (p = 0.008). In PSC, DNase1-activity was inversely associated with alkaline phosphatase (ALP) (p < 0.05). In AIH, complete responders were characterized by increased baseline DNase1-activity compared to partial responders, relapsers and non-responders (p < 0.02), whereas it was significantly increased after achievement of remission (p < 0.001). Serum DNase1-activity is significantly decreased in ALD patients, indicating its potential implication in their pathogenesis. Furthermore, DNase1-activity could be used as a new surrogate biomarker for predicting response to AIH treatment.
authors.affiliation: a Department of Medicine and Research Laboratory of Internal Medicine , School of Medicine, University of Thessaly , Larissa , Greece.
authors.forename: Nikolaos K
authors.initials: NK
authors.lastname: Gatselis
authors.affiliation: b Department of Pathophysiology , School of Medicine, National and Kapodistrian University of Athens , Athens , Greece.|c Department of Molecular Medicine , Hellenic Pasteur Institute , Athens , Greece , and.
authors.forename: Aigli G
authors.initials: AG
authors.lastname: Vakrakou
authors.affiliation: a Department of Medicine and Research Laboratory of Internal Medicine , School of Medicine, University of Thessaly , Larissa , Greece.
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Zachou
authors.affiliation: b Department of Pathophysiology , School of Medicine, National and Kapodistrian University of Athens , Athens , Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Androutsakos
authors.affiliation: a Department of Medicine and Research Laboratory of Internal Medicine , School of Medicine, University of Thessaly , Larissa , Greece.
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Azariadis
authors.affiliation: b Department of Pathophysiology , School of Medicine, National and Kapodistrian University of Athens , Athens , Greece.
authors.forename: Gregorios
authors.initials: G
authors.lastname: Hatzis
authors.affiliation: b Department of Pathophysiology , School of Medicine, National and Kapodistrian University of Athens , Athens , Greece.|c Department of Molecular Medicine , Hellenic Pasteur Institute , Athens , Greece , and.|d Joint Academic Rheumatology Program, National and Kapodistrian University of Athens , Athens , Greece.
authors.forename: Menelaos N
authors.initials: MN
authors.lastname: Manoussakis
authors.affiliation: a Department of Medicine and Research Laboratory of Internal Medicine , School of Medicine, University of Thessaly , Larissa , Greece.
authors.forename: George N
authors.initials: GN
authors.lastname: Dalekos
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D015551:Autoimmunity; D015415:Biomarkers; D001706:Biopsy; D003850:Deoxyribonuclease I / Q000097:blood*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D008875:Middle Aged
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D003850:Deoxyribonuclease I
keywords: Liver autoimmunity; apoptosis; autoimmune hepatitis; deoxyribonuclease1; primary biliary cirrhosis; primary sclerosing cholangitis