Scientists identify biomarkers that indicate likelihood of survival in infected patients
News Release
November 16, 2017 
RICHLAND, Wash. - Scientists have identified a set of biomarkers that indicate which patients infected with the Ebola virus are most at risk of dying from the disease.
The results come from scientists at the D.O.E.'s Pacific Northwest National Lab and their colleagues at the University of Wisconsin-Madison, Icahn School of Medicine at Mount Sinai, the University of Tokyo and the University of Sierra Leone. The results were published online Nov. 16 in the journal Cell Host & Microbe.
The findings could allow clinicians to prioritize the scarce treatment resources accessible and provide them to the sickest patients, said the senior author of the study, Yoshihiro Kawaoka, a virology professor at the UW-Madison School of Veterinary Medicine.
The focus of the study were blood samples from Ebola patients that were obtained during the outbreak in Sierra Leone in 2014. The Wisconsin team obtained 29 blood samples from eleven patients who ultimately survived and 9 blood samples from 9 patients who died from the virus. The Wisconsin team inactivated the virus according to approved protocols, developed in part at PNNL, and then shipped the samples to PNNL and other institutions for analysis.
The team looked at activity levels of genes and proteins as well as the amounts of lipids and byproducts of metabolism. The team found eleven biomarkers that distinguish fatal infections from non-fatal ones and 2 that, when screened for early upon symptom onset, accurately predict which patients are likely to die.
"Our team studied thousands of molecular clues in each of these samples, sifting through extensive data on the activity of genes, proteins, and other molecules to identify those of most interest," said Katrina Waters, the leader of the PNNL team and a corresponding author of the paper. "This may be the most thorough analysis yet of blood samples of patients infected with the Ebola virus."
The team found that survivors had higher levels of some immune-related molecules and lower levels of others compared to those who died. Plasma cytokines, which are involved in immunity and stress response, were higher in the blood of people who perished. Fatal cases had unique metabolic responses compared to survivors, higher levels of virus, changes to plasma lipids involved in processes like blood coagulation, and more pronounced activation of some types of immune cells.
Pancreatic enzymes also leaked into the blood of patients who died, suggesting that these enzymes contribute to the tissue damage characteristic of fatal Ebola virus disease.
The scientists found that levels of 2 biomarkers, known as L-threonine (an amino acid) and vitamin-D-binding-protein, may accurately predict which patients live and which die. Both were present at lower levels at the time of admission in the patients who ultimately perished.
The team found that many of the molecular signals present in the blood of sick, infected patients overlap with sepsis, a condition in which the body - in response to infection by bacteria or other pathogens - mounts a damaging inflammatory reaction.
Fifteen PNNL scientists contributed to the study. Among the corresponding authors of the study are 3 PNNL scientists: Waters, Thomas Metz and Richard D. Smith. 3 additional PNNL scientists - Jason P. Wendler, Jennifer E. Kyle and Kristin E. Burnum-Johnson - are among 6 scientists who share "first author" honors.
Other PNNL authors include Jon Jacobs, Young-Mo Kim, Cameron Casey, Kelly Stratton, Bobbie-Jo Webb-Robertson, Marina Gritsenko, Matthew Monroe, Karl Weitz, and Anil Shukla.
Analyses of proteins, lipids and metabolites in the blood samples were performed at EMSL, the Environmental Molecular Sciences Laboratory, a D.O.E. Office of Science User Facility at PNNL.
The study was funded by a Japanese Health and Labor Sciences Research Grant; by grants for Scientific Research on Innovative Areas from the Ministry of Education, Cultures, Sports, Science and Technology of Japan; by Emerging/Re-emerging Infectious Diseases Plan of Japan; and by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. Support was also provided by the Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai and by a grant from the National Institute of General Medicine.
Reference:
Amie J. Eisfeld and others, Multi-platform 'Omics Analysis of Human Ebola Virus Disease Pathogenesis, Cell Host & Microbe, Nov. 16, 2017, https://doi.org/10.1016/j.chom.2017.10.011.
Tags: Fundamental Science, EMSL, Biology, Molecular Biology and Biochemistry, Mass Spectrometry and Separations, Proteomics, Microbiology
EMSL, the Environmental Molecular Sciences Lab, is a D.O.E. Office of Science User Facility. Located at Pacific Northwest National Lab in Richland, Wash., EMSL offers an open, collaborative environment for scientific discovery to researchers around the world. Its integrated computational and experimental resources enable researchers to realize important scientific insights and create new technologies. Follow EMSL on Facebook, LinkedIn and Twitter.
Interdisciplinary teams at Pacific Northwest National Lab address many of America's most pressing issues in energy, the environment and national security through advances in basic and applied science. Founded in 1965, PNNL employs 4,400 staff and has an yearly budget of nearly $1 billion. It is managed and operated by Battelle for the D.O.E.'s Office of Science. As the single biggest supporter of basic research in the physical sciences in the United States, the Office of Science is working to address some of the most pressing challenges of our time. For more information on PNNL, visit the PNNL News Center, or follow PNNL on Facebook, Google+, Instagram, LinkedIn and Twitter.
