Alicja Bauer, Poland
Centre of Postgraduate Medical Education Department of Biochemistry and Molecular BiologyPresenter of 2 Presentations
SERUM MATRIX METALLOPROTEINASE-3 CONCENTRATION IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS
Abstract
Background and Aims
Matrix metalloproteinase (MMP)-3 plays an important role in connective tissue remodeling, degradation of collagen types II, III, IV, IX, and X, proteoglycans, fibronectin, laminin, and elastin. In addition, MMP-3 can also activate other MMPs such as MMP-1, MMP-7, and MMP-9. Primary biliary cholangitis (PBC) is a cholestatic, autoimmune liver disease, characterized by the progressive destruction of intrahepatic bile ducts, leading to cholestasis, fibrosis, cirrhosis, and liver failure. During fibrosis the balance between production and degradation of the extracellular matrix surrounding hepatocytes is disturbed.
Our aims in the present study were to determine whether the measurement of serum MMP-3 is clinically useful for assessing ongoing liver fibrolysis in patients with PBC
Methods
Matrix metalloproteinase (MMP)-3 concentration was determined by commercially available ELISA kit (AESKU, Germany) in 70 PBC patients and 30 healthy controls.
Results
The frequencies of PBC patients with higher MMP-3 levels were 60%. PBC patients had greater MMP-3 levels than healthy controls (92.7 ± 118.9 versus 20.8 ±15.7 ng/ml, p< 0.001). Serum MMP-3 levels were significantly elevated in patients with higher bilirubin concentration (120.3 ± 119.2 vs. 66.5 ± 41.8 ng/mL, P< 0.01) and correlated with specific for PBC anti-nuclear autoantibodies.
Conclusions
Our study demonstrated significantly higher MMP-3 levels in PBC patients than in healthy controls and positive correlation with various clinical parameters. Serum MMP-3 was associated with hepatic dysfunction and could play a role in the pathophysiology of hepatic fibrosis in PBC.
DIAGNOSTIC AND CLINICAL SIGNIFICANCE OF ANTI-KELCH-LIKE 12 AUTOANTIBODIES IN THE PRIMARY BILIARY CHOLANGITIS
Abstract
Background and Aims
Primary biliary cholangitis (PBC) is a slowly progressing cholestatic, autoimmune liver disease, characterized by the presence of anti-mitochondrial (AMA) and antinuclear antibodies (ANA) in the patients sera. The aim of the study was to determine the autoantibodies reactive against novel potential autoantigen in PBC - kelch-like 12 (KLHL12) protein in a well characterized cohort of PBC patients and compare them with other specific autoantibodies and biochemical parameters.
Methods
Study population - 92 PBC patients, 30 pathological controls – 20 primary sclerosing cholangitis (PSC) and 10 autoimmune hepatitis (AIH) patients, 30 healthy blood donors.
AMA, anti-Sp100 and anti-gp210 were detected by commercially available kits (IMTEC-Human, Euroimmun; Germany and Inova Diagnostics; USA). The presence of anti- KLHL12 antibody was determined by an” in-house” ELISA technique using a full-length recombinant human KLHL12 protein.
Results
Anti-KLHL12 antibodies were detected in 35% of the total cohort of PBC patients, including AMA-negative PBC. They were found more frequently in PBC compared with non-PBC disease controls (P < 0.001). Specificity and positive predictive values of this test for PBC were 98% and 96%, respectively. We found anti-KLHL12 antibodies together with anti-Sp100 and/or anti-gp210 in 59 (64%) cases. Presence of anti-KLHL12 was associated with higher concentration of bilirubin and correlate with fibrosis (P<0.05).
Conclusions
Antibodies against KLHL12 protein are highly specific for PBC. The combination of anti-KLHL12 with other markers can increase the diagnostic sensitivity on PBC. Coexistence of different antibodies suggests an autoimmune reaction against multiple nuclear components in some of PBC patients.