LEBANON, NH – Sepsis kills a quarter of a million Americans each year – as many as stroke and Alzheimer’s combined – but very little has changed in the treatment of this age-old scourge. Now an international group of researchers including Dartmouth-Hitchcock Medical Center (D-H) may have identified a simple blood test that could identify patients at greatest risk of dying from sepsis, a condition that has long defied treatment. The discovery, published in Nature, could save thousands of lives each year.
For most people, the immune system is incredibly effective at dealing with minor injuries such as scrapes and cuts. The body is able to wall of and clear an infection. But, when that system fails, a local infection can spread throughout the bloodstream, creating the condition known as sepsis. The body’s life-threatening reaction is known as septic shock and it can quickly kill the patient. Numerous treatments attempt to save the patients by targeting the overzealous immune response, but they have been largely ineffective in saving lives.
Researchers may have determined how sustained inflammation from a sepsis infection can trigger immunoparalysis, a condition in which patients are at much higher risk of new infections because their immune system is not capable of responding to new threats. The research team, including Matthew S. Hayden M.D., Ph.D, a senior scientist in Dermatology at D-H, identified two tiny pieces of genetic code known as microRNAs (miR-221 and miR-222) that are produced in immune cells during prolonged inflammation.
“When cells of the immune system are exposed to bacterial products for long periods of time, they increase their expression of these two small RNAs, which target a part of the cellular machinery that is needed for the inflammatory response,” Hayden explains. “As a result, when immune cells have high levels of these microRNAs, as they do in some sepsis patients, they are no longer effective at fighting off new infections.”
Testing for sepsis is not easy. The problem has been pinpointing what is causing the massive infection and applying the right treatment without doing more harm to the patient. Many patients who survive this initial spread of infection remain at significant risk of death, partly because their immune system is almost paralyzed.
“The best treatment for sepsis starts with rapid detection. Our results suggest that specific molecules called microRNAs may be potential biomarkers of poor prognosis, indicating the need for more aggressive treatment options,” explains the study’s senior leader Sankar Ghosh, PhD, the chair of the Department of Microbiology & Immunology at Columbia University Vagelos College of Physicians and Surgeons.
The researchers have now shown that sepsis patients have higher levels of these microRNAs and are more likely to experience organ failure and immunosuppression. A simple blood test looking for these tiny particles may help identify the highest-risk sepsis patients. That could help identify therapies that help to reinvigorate the immune system by reversing immunoparalysis in order to prevent the secondary infections in sepsis patients.
Clinical trials will test the validity and usefulness of testing patients for these microRNAs as a quick guide to prognosis and treatment. The research comes at a time when the number of sepsis cases per year has been on the rise in the United States, according to the National Institute of Health. Creating better diagnostics may be able to help reverse this trend and save lives.
The study, published in Nature, is titled, “Induction of innate immune memory via microRNA targeting of chromatin remodelling factors.”