The results of a study that identified the genetic factors of primary biliary cholangitis, an autoimmune liver disease, have been published.
Kangnam Severance Hospital Department of Laboratory Medicine Professor Lee Kyung-ah, Yonsei University College of Medicine Department of Biomedical Science Professor Kim Lak-gyun and Do So-hee, Yonsei University College of Medicine Department of Laboratory Medicine Professor Shin Sae-am, Hallym University Gangnam Sacred Heart Hospital Professor Park Sang-hoon and the research team -10)’ and presented the results of a study that identified the relationship between
The results of this study were published in an international journal
According to him, autoimmune liver disease is a disease that causes inflammation on its own by judging one’s own liver cells as pathogens beyond the immune system. It accounts for about 5% of all liver diseases. Primary biliary cholangitis (PBC) is a disease in which inflammation in the portal vein and bile duct damage in the liver progress chronically, resulting in cholestasis, which leads to hepatocellular destruction and fibrosis, leading to cirrhosis.
Although the pathogenesis of PBC has not been precisely identified, it is known that environmental factors such as infections and chemicals and genetic factors affect it.
The research team analyzed the genome of a rare family in which all four sisters in the same family were diagnosed with PBC to identify the genetic factors associated with the onset of PBC. As a result, it was confirmed that there was a mutation in the ‘caspase-10’ gene of the sisters. In addition, as a result of analyzing the nucleotide sequences of 62 patients with PBC, it was confirmed that mutations in caspase-10 were observed at a frequency 10 times higher (P=0.002) in PBC patients than in the general population.
Caspase is a proteolytic enzyme involved in cell death, inflammation, and autoimmunity, and acts as an important factor in tumor development and autoimmune diseases. However, little is known about the function of caspase-10 in the human body.
Accordingly, the research team utilized the CRISPR/Cas9 technology, a gene editing technology, to identify the role of caspase-10 in the pathogenesis of PBC. A cell line from which -8 was removed and a cell line from which caspase-10 gene was removed were created and compared to each other to investigate the differences.
As a result, it was found that unlike caspase-8, caspase-10 does not play a significant role during the process of differentiation into macrophages, but strongly regulates the inflammatory cell death process after differentiation.
In addition, it was confirmed that liver fibrosis can be promoted in macrophages in which the caspase-10 gene has been deleted, and that this progression can be inhibited by administering ursodeoxycholic acid and obeticholic acid, which are currently approved as PBC treatment drugs. .
Professor Rakkyun Kim said, “This study is the first to identify that defects in caspase-10 function in macrophages affect PBC pathogenesis.” We hope to be able to present it,” he said.