Protein “switch” could be key to controlling blood poisoning

Scientists at the University of British Columbia have discovered a new protein “switch” that could stop the progression of sepsis and increase the chances of surviving the life-threatening disease. Sepsis causes an estimated 14 million deaths every year. In a study published recently in Immunity, researchers examined the role of a protein called ABCF1 in regulating the progression of sepsis. Researchers discovered that ABCF1 acts as a “switch” at the molecular level that can stop the uncontrolled chain-reaction of inflammation in the body and dampen the potential damage. With no specific course of treatment, management of sepsis for the 30 million people who develop it each year relies on infection control and organ-function support.

Though sepsis is hard to diagnose, scientists do know that it occurs in two phases. The first phase, systemic inflammatory response syndrome (SIRS), results in a “cytokine storm,” a dramatic increase in immune cells such as macrophages, a type of white blood cell. This results in inflammation and a decrease in anti-inflammatory cells, leading to chemical imbalances in blood and damage to tissues and organs. Recovery starts to take place when the body enters a second phase (endotoxtin tolerance, or ET), where the opposite occurs.

Building on previous knowledge of ABCF1 as part of a family of proteins that plays a key role in the immune system, researchers examined its role in white blood cells during inflammation in a mouse model of sepsis. They discovered that ABCF1 had the ability to act as a “switch” in sepsis to transition from the initial SIRS phase into the ET phase and regulate the “cytokine storm.” Furthermore, without the ABCF1 switch, immune responses are stalled in the SIRS phase, causing severe tissue damage and death.

The discovery opens up potential for new treatments for chronic and acute inflammatory diseases, as well as autoimmune diseases.

The research was conducted in collaboration with the Vancouver Prostate Centre, a Vancouver Coastal Health Research Institute research centre, and was funded by the Canadian Institutes of Health Research. The article is available online at https://doi.org/10.1016/j.immuni.2019.01.014.