A Signpost for Sepsis

Norbert: Dave, do you know what's responsible for half of all hospital deaths in America?

Dave: I don't know... heart failure?

Norbert: No, it's sepsis!

Dave: Ah... of course! Sepsis is when the body's immune system overreacts to an infection and begins attacking its own organs and tissues. But it's possible scientists have identified the biomarker that can predict who's at risk of dying from sepsis so doctors can intervene earlier.

Sepsis can be triggered by any kind of an infection, including viruses, bacteria, fungi and parasites. Very early in sepsis, the immune system produces large amounts of various proteins to ramp up the immune response. One is a powerful process called pyroptosis which destroys infected cells. But it also fuels the development of sepsis.

When scientists looked for genetic variations that made people more susceptible to pyroptosis, they identified a single change in DNA that creates a molecule called methylthioadenosine or MTA. Scientists hypothesized that MTA levels can predict who would die of sepsis, and changing its levels can increase survival.

Early in infections, its level in the blood goes up, but falls in tissues. But if an infection isn't dealt with, more MTA is released, which indicates an out of control immune system. Indeed, in 62 patients, the chances of dying from sepsis were increased over seven times when MTA levels are doubled. But in their experiments with mice, those treated with MTA before a bacterial infection lived longer. The key is to find out when to raise and lower MTA levels during sepsis to improve survival.