New biomarkers identify trauma patients at risk for chronic critical illness

New research, published in The Journal of Immunology, identified biomarkers of a distinct immune profile that could be used to identify patients at risk for chronic critical illness (CCI) upon admittance to the intensive-care unit (ICU) after traumatic injury. Identifying which patients are at increased risk for CCI could allow doctors to intervene earlier, leading to shorter ICU stays and improved patient outcomes. 

Our findings are highly novel, challenging what scientists have long thought about the immune changes that cause organ dysfunction and mortality in severely injured trauma patients. Rather than the immune system being exhausted, our data show overactivity and dysfunction."

Dr. Scott Brakenridge, Professor of Surgery, University of Washington and senior author for the study

Severe traumatic injury, such as from a car crash or fall, causes changes to the immune system that can lead to immune and organ dysfunction, as well as recurrent infections. Researchers have long thought this was due to deficiency in an immune signal, or cytokine, called interferon-gamma (IFN��), which regulates immune responses. While CCI, which describes patients who remain dependent on ICU care for more than 14 days, is related to these immune changes, clinicians did not know what drove the disease. 

This new research now shows that CCI patients exhibited increased numbers of immune cells including neutrophils, a type of T cell called Th17, and amplified inflammatory cytokines including IFN�� and IL-17A. These markers indicate a patient's immune system is inducing a misdirected or imbalanced response. This immune profile was distinctly different when compared to trauma patients who recovered within 14 days. 

"As the immune changes observed in CCI patients are distinct from patients who recover before 14 days, these findings reveal immunological features that may be used to quickly identify trauma patients at risk for CCI when they are admitted to the ICU. Developing a test for this profile would allow clinicians to tailor patient care, quickening recovery time and saving lives," shared Caleb Kim, PhD candidate at the University of Minnesota and first author of the paper. 

Traumatic injury triggers a dynamic immune response that can increase inflammation or immune dysregulation. Trauma patients are also susceptible to infections during their stay in the ICU, which can elongate or complicate their recovery. However, only about 20% of trauma patients develop CCI. 

To understand what drives CCI, researchers collected blood samples from blunt/penetrating trauma patients admitted to the ICU on days 4, 7, 10, 14, and 28 of their ICU stay or until they were discharged. Patients were sorted into groups based on the length of their stay with rapid recovery (RR) patients discharged within 7 days, intermediate (IM) patients discharged between day 7-14, and CCI patients admitted longer that 14 days. The researchers compared blood samples from the different groups to determine any differences that may explain why some patients developed CCI. 

"IL-17A was the most informative marker that distinguished CCI patients from RR or IM. Some CCI patients had elevated IL-17A even at day 1 in the ICU, suggesting almost immediate immune dysregulation," said Dr. Brakenridge. 

"Understanding that CCI patients do not simply experience an early failure of immunity but rather a misdirected or imbalanced response, is critical to developing early interventions to help patients at risk for CCI," continued Dr. Brakenridge. 

The researchers plan to build on these findings by further delineating the immune mechanisms driving CCI.