Immune-cell biomarker may provide early diagnosis tool for bacterial sepsis

BOSTON – Sepsis, a life-threatening immune response to infection, can lead to tissue damage, organ failure and amputation; its mortality rate is 15 to 34 percent, and it is the most expensive condition treated in U.S. hospitals, accounting for 13 percent of hospital costs and an estimated $62 billion annually.

Early detection is a major challenge in managing sepsis, largely because it is heterogeneous and symptoms are often vague and may not be obvious. But now, researchers at Massachusetts General Hospital (MGH), Brigham and Women’s Hospital, the Massachusetts Institute of Technology (MIT), and the Broad Institute of MIT and Harvard have come a step closer to early diagnosis of sepsis and perhaps to the development of treatments that can stop it before it even begins. The findings are described in the journal Nature Medicine.

“The underlying problem is an abnormal immune response,” said corresponding co-author Marcia B. Goldberg, MD, a physician and researcher in MGH’s Infectious Diseases Division, a member of the Broad Institute, and a professor at Harvard Medical School. To tease out the cause, she and her colleagues — a multidisciplinary team of immunologists, infectious disease doctors, and engineers, all affiliated with Broad — looked at a small sample of hospitalized patients in early sepsis and a control group who had infections without sepsis. “We identified a new subset of monocytes, or innate immune cells, that was markedly expanded in the patients with sepsis.”

The team also identified two genes that together serve as a strong biomarker of patients with sepsis, indicating the potential for even more unknown biomarkers to be uncovered.

“This subset of monocytes has the potential to enable us to learn much more about why the immune system is dysregulated,” Goldberg said. Though the scientists don’t yet know whether the MS1 cells, which they’ve called the newly identified monocytes, are causing the dysbiosis or are a result of it, just knowing they’re there is important for future research.

“Not only might this be a way to monitor patients with known infections to predict which of them will develop sepsis,” said Goldberg, “but it could also lead to medications that interfere with the dysbiosis and thereby treat sepsis more effectively than we currently do.” The team is currently seeking funding for a larger study. “Once we look at more patients,” Goldberg said, “we can dig deeper.”

The study’s co-authors are Miguel Reyes of MIT and the Broad Institute; Michael R. Filbin and Roby P. Bhattacharyya of MGH and the Broad Institute; Kianna Billman and Thomas Eisenhaure, both of the Broad Institute; Deborah T. Hung of Brigham and Women’s Hospital and the Broad Institute; Bruce D. Levy and Rebecca M. Baron, both of Brigham and Women’s Hospital; Paul C. Blainey of MIT and the Broad Institute; and Nir Hacohen of MGH and the Broad Institute.

About the Massachusetts General Hospital
Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $1 billion and comprises more than 8,500 researchers working across more than 30 institutes, centers and departments. In August 2019 the MGH was once again named #2 in the nation by U.S. News & World Report in its list of "America’s Best Hospitals."