A group of scientists led by Dr. Tomasz Kantyka from the Małopolska Center for Biotechnology at the Jagiellonian University, in collaboration with the Department of Microbiology at the Jagiellonian University, the University of Bergen, and the SOLARIS Center, is conducting research on the molecular mechanisms associated with rheumatoid arthritis (RA). This disease is an autoimmune disorder in which the immune system mistakenly attacks its own cells, leading to chronic inflammation and joint damage.
One of the characteristic features of RA is the presence of antibodies that recognize proteins containing citrulline, a modified form of the amino acid – arginine. The process of citrulline formation is influenced by the enzyme peptidyl arginine deiminase 4 (PAD4). Scientists are trying to investigate what causes the excessive activity of this enzyme and what environmental factors may promote the formation of citrullinated proteins, which then become targets for the immune system.
In the latest study, the team discovered that glycosaminoglycans—sugar-like molecules naturally found in the extracellular matrix of tissues, such as heparin, heparan sulfate, and chondroitin sulfate—can increase the activity of the PAD4 enzyme. Typically, this enzyme requires high calcium concentrations to function effectively. However, calcium levels in cells and tissues are too low to activate PAD4 on their own. The researchers showed that glycosaminoglycans can “help” the enzyme function even at physiological calcium levels.
Read more on the SOLARIS website
Image: PAD4 mechanism of action in rheumatoidal arthtitis (RA). PAD4 is responsible for citrulination of proteins. Interaction with glycosaminoglycans increases the citrulination level by increase calcium ions recruitment. This can lead to autoimmune degradation od health joint tissue.