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A multi-year clinical investigation successfully tested the hypothesis that novel viral microRNA biomarkers can help identify trauma patients at risk for poor outcomes early on in their trauma recovery.
These viral microRNAs can be detected within hours of injury, according to the recent study, “Cellular MicroRNAs Correlate with Clinical Parameters in Polytrauma Patients,” published in the journal Critical Care Medicine, which was funded and supported by the Uniformed Services University of the Health Sciences (USU) Surgical Critical Care Initiative (SC2i).
Dr. Thomas Davis, USU professor and vice chair of research in the Department of Surgery, said the multidisciplinary investigative team found that a number of viral encoded micro-RNAs that promote viral replication are elevated and detectable in the blood early after injury.
“The degree of reactivation and release of viral micro-RNAs coincides with the early acute inflammatory response and poor clinical outcomes in critically ill patients,” says Davis.
Team lead, USU associate professor Navy Cmdr. (Dr.) Diego Vicente, a surgical oncologist and part of
the 1st Medical Battalion based at Camp Pendleton, Calif., says one big discovery from the study is that latent viruses are reactivating early in response to trauma and these particles have the potential to propagate the immune response.
Messenger ribonucleic acid, or mRNA, is an essential molecule used in constructing proteins for cell growth. MicroRNAs are non-coding RNAs that are involved with the regulation of gene expression through inhibition of mRNAs. Some RNA viruses create viral microRNAs, which help it to avoid the host’s natural immune response.
“Previously, we thought these viruses were slow to reactivate in patients with suppressed immune systems from other severe illnesses, such as sepsis,” says Vicente. “The findings in this study have completely changed the paradigm in understanding the timing of viral re-activation and the implication for recovery in critically ill patients.”
Vicente began to study the inflammatory response to trauma in 2012 while he was working with wounded warriors at Walter Reed National Military Medical Center. “These combat trauma patients were really sick, and I knew that while the comprehensive biomarkers panels available at that time predicted some of the clinical outcomes, they did not explain the whole picture of the inflammatory response to trauma,” Vicente says.
According to Vicente, while evaluating these same biomarkers panels to characterize the inflammatory response to surgery in patients at MD Anderson Cancer Center, his collaborators recommended they consider evaluating microRNAs in trauma patients, as these had demonstrated some predictive value in cancer patients and septic patients.
“That was the genesis of the SC2i microRNA project,” says Vicente. “My background in combat trauma studies contributed to my cancer research, and ultimately considering the inflammatory response in cancer patients translated back to identify novel microRNAs in trauma patients,” Vicente says. “From this initial idea, we developed a collaboration between SC2i and MD Anderson Cancer Center and had the opportunity to mentor investigators in a novel area of research.”
One of the study’s co-authors Dr. George Calin, a professor at MD Anderson Cancer Center and microRNA subject matter expert says this discovery could benefit people in the future by screening them beforehand for viral microRNAs.
“Specifically, before deployment, the military personnel can be screened for viral microRNAs and this information can be included in the medical record,” says Calin. “If, unfortunately, they suffered from severe traumatic injury, the ones with positivity for the viral microRNAs could be on the most aggressive therapy.”
Calin says one of the most interesting discoveries from the study was that the microRNAs in question are not generated from the human genome but from the viral genomes of Epstein Barr virus and Kaposi Sarcoma virus.
Calin adds immediately after the traumatic injury, the viral microRNA test can potentially be done in the future using a field PCR machine, used to amplify small segments of DNA or RNA, so the patients can be monitored daily for the evolution of viral microRNAs.
“Measuring the early expression of microRNAs in our critically injured service members may serve as an additive strategy to improve risk-stratified patient management with the aim to improve the prediction accuracy of individual patient health outcomes,” says Davis.
According to Vicente, there’s huge therapeutic potential in this discovery with the next steps including moving the clinical studies back to the research lab.
“If we can figure out how to manipulate these microRNA signaling molecules, we would have a new way of regulating inflammation,” says Vicente. “Which has not been done in the world of trauma. The adaptation for this in trauma is prime for studying.”
The study received the prestigious Critical Care award from the American Association of Surgeons of Trauma during the 80th annual conference in October.
| Date Taken: | 12.14.2021 |
| Date Posted: | 12.14.2021 09:30 |
| Story ID: | 411055 |
| Location: | BETHESDA, MARYLAND, US |
| Web Views: | 663 |
| Downloads: | 1 |
This work, Study Finds Viral MicroRNA Biomarkers Elevated, Detectable in Blood After Traumatic Injury, by Ian Neligh, identified by DVIDS, must comply with the restrictions shown on https://www.dvidshub.net/about/copyright.
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