As an anesthesiologist, Dr. Martin Angst of Stanford University medical school wanted to know why some of the patients he treated bounced right back after surgery while others only inched back to normalcy.
Angst teamed up with Stanford professor of immunology and microbiology Garry Nolan to study 32 patients between the ages of 50 and 80 as they recovered from hip replacement surgery. Although the patients had the same surgery, the same initial health status, and the same anesthesia drugs, their recovery times varied widely.
Using a method called single-cell mass cytometry, the researchers identified a signature blood test result that predicted which patients would recover quickly from surgery and which would struggle. They published their findings today in the journal Science Translational Medicine.
The researchers surveyed the immune system in the hours following surgery. They found that if the activity of monocytes — considered the immune system’s “first responders” — peaked immediately following surgery but fell 24 hours after surgery, the patient would recover well. If the cells were still very active after 24 hours, the patient would have a more difficult recovery.
The initial blast of inflammation is a healthy way for the body to respond to trauma, said Angst. The trouble comes if it doesn’t serve its purpose and then dissipates.
“You need to unleash the dragon, but then you need to be able to ride it, because if it goes out of control you may recover much more slowly,” Angst said.
The monocytes make up just 1 to 2 percent of the white blood cells in a healthy person's blood, but their immune signature accounted for roughly half of the difference in how well patients healed. The patients reported in detail how well they were feeling every three days for six weeks after their surgery.
The same test could also be used to predict how well soldiers or athletes will recover from injuries.
“You can visualize the operating room as the perfect place to study injury and how we recover from injury under fairly well controlled circumstances,” Angst said.
Working Toward ‘A Simple Lab Test’
The next step is to find similar markers of recovery earlier. Ideally, surgical patients could learn before surgery how long it might take them to recover.
Angst, Nolan, and their colleagues at Stanford are already looking for telltale immune activity before surgery. They are using chemicals to challenge the immune system, essentially giving it a stress test to see how it responds.
Ideally, they’d like to “dilute it down to a simple lab test,” Angst said. Stanford has optimistically gotten a provisional patent on any such tests.
Knowing immediately after surgery how well a person will recover is a convenience. But knowing beforehand could be a game changer. There are more than 200 million surgeries around the world every year, a 2008 study found.
“You could stratify patients, educate them about risk factors. You might even be able to modify their immune system to turn them in to faster recoverers,” Angst said.
A Detailed Picture of the Immune System at Work
Single-cell mass cytometry could be used to solve a number of mysteries about the immune system.
The method gives researchers a “snapshot” not just of what kinds of immune cells are in the blood, but also what they are doing.
By using a different method to poke and prod cells than conventional cytometry, Nolan’s method means researchers can look at more parameters in their studies. They don’t have to know in advance what they’re looking for; instead they can conduct a broad survey.
If our current understanding of the immune system is like a schematic road map, these results promise to be more like satellite imagery.
Immune health is a hot topic. Grocery store aisles full of dietary supplements promise to boost immune health, but doctors don’t really know what a robust immune system looks like.
“There’s no way to measure immune fitness, and this is what we tried to accomplish,” Angst said.
The nuances of how the immune system works are also very much in play in research on HIV and cancer. Nolan is already looking at using the system he developed to support research into immunotherapies for cancer.