Sepsis is a deadly complication that results from the immune system attacking organs and tissues after an infection. It is hard to diagnose and may be involved in the deaths of a quarter million people in the U.S. every year. Scientists have identified a new biomarker that can be used to find patients likely to have sepsis, and possibly even prevent it.
Sepsis can be triggered by any kind of infection, and even hospitalized sepsis patients have mortality rates of up to 30 percent. There have been more than 100 failed clinical trials of ways to treat sepsis. Part of the difficulty has been identifying which immune responses will lead to sepsis. Without better ways to identify sepsis and decide how the immune system should be manipulated, it is difficult to know whether a sepsis treatment failed or was simply the wrong choice for an individual patient.
Sepsis treatment includes supportive care and drugs for the infection. In early stages, the immune system produces a series of proteins that kill infected cells in a process called pyroptosis. The problem is that pyroptosis also fuels the immune response, contributing to the development of sepsis. Scientists looked for natural genetic variations and found a single change in DNA that made people more susceptible to sepsis. It was in a process that the body uses to recycle an amino acid called methionine, and one of the products of that process is methylthioadenosine (MTA).
Scientists hypothesized that MTA could control the immune response and could be used to predict who would die of sepsis. They found that high levels of MTA in the blood helped predict death from sepsis. In 62 patients, the chances of dying from sepsis were increased over seven times when MTA levels were doubled. This is comparable to the accuracy of the current scoring system used to predict the outcome of sepsis in patients in the intensive care unit. Because measurement of MTA levels is specific for infection, it could be a better marker for predicting the outcome of sepsis.
MTA may be a marker for the runaway immune response that is thought to lead to death from sepsis. In early stages of infection, MTA levels in the blood increase but decrease in tissues. Scientists speculate that elevated MTA levels may be involved in limiting the immune response. If an infection is not effectively dealt with, more MTA is released, indicating an out-of-control immune response trying to deal with a major infection.
Scientists also wondered if they could manipulate MTA levels to alter the outcome of sepsis. Mice treated with MTA before infection with a deadly Salmonella bacterium lived longer, suggesting that MTA could work as therapy. The best timing for MTA therapies is still unknown. Sepsis patients at early stages of the disease might benefit from treatments that increase the immune response, whereas patients at later stages might benefit from therapies that decrease it.
Measuring MTA levels may be a new tool that could help determine the treatment of more than one million sepsis patients in the United States every year, and millions more throughout the world.