Clues about Immune Resolution Identified in Blood
New profiling procedure identifies immunoresolvents in coagulated human blood
Stopping a wound from bleeding is essential for human health. Blood coagulation – in which blood goes from liquid to gel and forms a clot – can prevent excessive bleeding and infection. But exactly what molecular events transpire when blood coagulates has remained somewhat mysterious. Using a new profiling procedure invented by investigators from Brigham and Women’s Hospital permitted them to elucidate the role of immunoresolvents – molecules that help resolve inflammation and infections –in blood coagulation, identifying a new cluster of these molecules that are produced when blood coagulates. The team’s findings are published online in Science Signaling.
“We’ve identified factors biosynthesized by human blood coagulation that elicit immune responses that protect the host,” said corresponding author Charles N. Serhan, PhD, DSc. director and principal investigator at the Center for Experimental Therapeutics and Reperfusion Injury at BWH. “Our results uncover a previously uncharacterized connection between the coagulation of blood and innate host defense mechanisms. We’ve demonstrated for the first time how the innate immune response is connected to coagulation via novel pro-resolving mediators.”
The new profiling procedure allowed the team to identify a cluster of immunoresolvents, namely resolvin D1, resolvin D5, resolvin E1, lipoxin B4 and maresin 1. These molecules activate immune cells called phagocytes, which can engulf and kill bacteria in the blood. Treating human blood with the components of this cluster of molecules discovered at BWH enhanced the abilities of phagocytes and helped the immune system attack E. coli, a common source of bacterial infection.
Interestingly, the newly developed profiling technique holds potential for profiling immunoresolvants in many contexts. The current study offers a glimpse of immunoresolvents found in the blood of healthy individuals, but the researchers are also interested in studying blood samples from patients with sepsis to pinpoint differences in immunoresolvents. Beyond blood, the research team also found a distinct profile of immunoresolvents in samples of healthy versus cancerous tissue from the testes – they note that this new profiling technique could potentially be used in the future to help distinguish between cancerous and healthy tissue from the testes or elsewhere in the body.
This work was supported, in part, by the National Institutes of Health (grant numbers R01GM38765, R01GM38765-29S1, and P01GM095467).
Paper cited: P. C. Norris, S. Libreros, N. Chiang, C. N. Serhan, “A cluster of immunoresolvents links coagulation to innate host defense in human blood.” Sci. Signal. 10, eaan1471 (2017).
Kidney Disease Risk Score Can Be Built Into Patients’ Electronic Health Records
More than 26 million Americans have chronic kidney disease (CKD). Primary care physicians who take care of these patients can help reduce the risk of complications and death if they recognize the progression of kidney failure early, but this is often difficult to do – deterioration can be rapid and more than one laboratory test may be needed to accurately predict a patient’s risk. A new electronic health record (EHR) tool could help physicians quickly and accurately flag patients that should be referred to a nephrologist. Designed by Brigham and Women’s Hospital investigators, this tool draws upon recent research that has identified several tests that can be used to calculate an individual’s risk score. Now, an automatic calculator can be built into EHRs and displayed prominently for a physician to see when they open a patient’s record. The tool was piloted at ten North Shore Physicians Group clinics this year, and a paper detailing the design and implementation of the application appear online this week in The Journal of the American Medical Informatics Association.
“Retrospective studies of patients who have had to go on dialysis show that being referred to a nephrologist just a few months earlier can have major benefits,” said corresponding author Lipika Samal, MD, MPH, a clinician investigator in the Division of General Internal Medicine. “We want to make it as easy as possible for a physician to quickly access and track a patient’s risk. This tool automatically calculates and displays a risk score within the health record, making it easier for a physician to spot disease progression and take action.”
The new clinical decision support tool calculates and displays kidney failure risk based on criteria identified from a large cohort study conducted by Canadian researchers (Tangri et al., 2011). Predictive risk factors that go into the calculation include serum and urine tests that collected during routine care. If test results for any of these predictive measures have not been collected and are not in a patient’s record at the time of a visit, the tool will display a recommendation to order the tests. Otherwise, the tool will display a five-year kidney disease risk score, and if the risk is high, a recommendation for a referral to a nephrologist.
The tool was deployed outside of the EHR in a way that would allow it to be used with different EHRs by utilizing interoperability standards called continuity of care documents (CCDs). The tool extracted the necessary tests from this interoperable document.
The research team validated the tool in 255 patients and subsequently deployed it to 10 primary care clinics. The team made improvements and updates to the tool based on feedback from physicians. In the course of the pilot, they processed more than half a million CCDs to diagnose CKD and to generate risk scores for patients with CKD.
Because of the interoperable nature of the tool, the team sees an opportunity to deploy this single application across multiple EHRs. They plan to implement it in eCare at BWH later this year. Samal also envisions applications for clinical decision support tools beyond CKD.
“One of the positive things about EHRs is that there is now a wealth of data that can be used to help us better predict an individual’s risk, especially for chronic and progressive diseases, like CKD,” said Samal. “We have the opportunity to use EHRs to improve patient care– tools like this one can help us seize that opportunity.”
This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award no. K23DK097187.
Paper cited: Samal L et al. “Implementation of a scalable, web-based, automated clinical decision support risk-prediction tool for chronic kidney disease using C-CDA and application programming interfaces” Journal of the American Medical Informatics Association DOI: 10.1093/jamia/ocx065