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Decreased serum DNase1-activity in patients with autoimmune liver diseases

Nikolaos K Gatselis1, Aigli G Vakrakou2,3, Kalliopi Zachou1

  • 1a Department of Medicine and Research Laboratory of Internal Medicine , School of Medicine, University of Thessaly , Larissa , Greece.

Autoimmunity
|March 7, 2017
PubMed

Insights

Serum deoxyribonuclease 1 (DNase1) activity is significantly lower in patients with autoimmune liver diseases (ALD), suggesting its role in disease pathogenesis. Lower baseline DNase1 activity may predict treatment response in autoimmune hepatitis (AIH).

Area of Science:

  • Immunology
  • Hepatology
  • Biochemistry

Background:

  • Deoxyribonuclease 1 (DNase1) is crucial for clearing self-DNA from apoptotic cells, preventing autoimmune responses.
  • DNase1 deficiency can lead to DNA accumulation, potentially triggering inflammation and autoimmunity.
  • Autoimmune liver diseases (ALD) encompass autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC).

Purpose of the Study:

  • To investigate serum DNase1 activity in treatment-naïve patients with AIH, PBC, and PSC for the first time.
  • To compare DNase1 activity in ALD patients with those suffering from viral hepatitis, nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH), and healthy controls.
  • To explore the correlation between DNase1 activity and disease markers, and its potential as a predictive biomarker for treatment response in AIH.

Main Methods:

  • Serum DNase1 activity was measured using single radial enzyme-diffusion (SRED) in 224 AIH, 249 PBC, and 36 PSC patients.
  • Control groups included 146 patients with viral hepatitis, 140 with NAFLD/NASH, and 114 healthy individuals.
  • Paired analyses were performed on serum samples from AIH and PBC patients during remission.

Main Results:

  • Serum DNase1 activity was significantly lower in patients with AIH, PBC, and PSC compared to viral hepatitis, NAFLD/NASH, and healthy controls (p < 0.05).
  • No significant differences in DNase1 activity were observed among the specific ALD subtypes.
  • In AIH, DNase1 activity correlated positively with AST, bilirubin, and elevated IgG. In PBC, it correlated with AST, ALT, and AMA. In PSC, it was inversely associated with ALP.
  • Higher baseline DNase1 activity in AIH patients predicted a better response to treatment, and activity increased significantly upon achieving remission.

Conclusions:

  • Serum DNase1 activity is markedly reduced in patients with autoimmune liver diseases, suggesting a role in their pathogenesis.
  • DNase1 activity may serve as a novel surrogate biomarker for predicting treatment response in autoimmune hepatitis (AIH).
Keywords:
Liver autoimmunityapoptosisautoimmune hepatitisdeoxyribonuclease1primary biliary cirrhosisprimary sclerosing cholangitis

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