Measurement of Neutrophil Motility may Have Predictive Value in Sepsis

New microfluidic device developed by scientists at the Massachusetts General Hospital (MGH) accurately measures migration patterns of neutrophils (a type of white blood cell important in the immune response). Measurement of neutrophil motility in a single drop of blood has been found to be able to predict patients at risk of developing sepsis so that appropriate treatment measures can be instituted to prevent its occurrence. The findings of the study appear in the journal Nature Biomedical Engineering.

"We found that neutrophils from sepsis patients exhibit specific spontaneous migration patterns when tested in whole blood samples," says Felix Ellett, PhD, a postdoctoral fellow in the BioMEMS Resource Center in the MGH Department of Surgery, lead author of the study.

"During sepsis, factors present in the plasma of these patients induce neutrophils to migrate spontaneously when placed into the mazes of our microfluidic device, and we were able to identify migration patterns specific to sepsis."

Reason for Study

Impaired neutrophil function has long been known to be an important reason for occurrence of sepsis. However, there are currently no methods to accurately measure neutrophil function to predict or diagnose sepsis accurately.

The newly designed microfluidic device hopes to overcome this critical gap and enable precise and early diagnosis and treatment of sepsis which would vastly improve patient prognosis and outcome.

• Daniel Irimia, MD, PhD, associate director of the BioMEMS Resource Center and senior author of the current study had earlier led a study in 2014 which found that measuring movement patterns of isolated neutrophils, (including rapid, spontaneous motion not stimulated by a chemical attractant), could accurately predict those patients who were likely to develop sepsis.
• The authors of the current study believed that the results of earlier study (2014) on isolated neutrophils could be further validated in blood samples obtained from seriously ill patients.

Methods of the Study

• Blood samples obtained from 23 patients under intensive care at various periods of hospitalization were assessed for neutrophil motility patterns using the special micro fluid device
• The newly developed microfluidic device - around 5 millimeters in diameter,  is made up of a central chamber surrounded by filters that prevent red blood cells and other blood components from passing through
• Only neutrophils can pass through the filters and reach a maze of channels within which their motility patterns can be studied
• The research team identified and measured five neutrophil parameters, namely, the number of neutrophils, their movements within the channels, the time spent remaining immobile, reverse movement back into the central chamber, and the average distance migrated.

These five parameters were used to establish a ‘Sepsis Score’ to predict those patients who were at risk for developing sepsis or had sepsis.

• The initial observations were reconfirmed by testing samples from a separate group of 19 patients from another ICU; results showed more than 95 percent accuracy in identifying patients at risk of or having sepsis

Thus the findings of the study underline the importance of impaired neutrophil function during sepsis.

"Using blood samples taken from patients on the first day of hospitalization, the assay identified sepsis patients with very high accuracy" says Jarone Lee, MD, medical director of the Blake 12 Intensive Care Unit at MGH and a co-author of the report. "We believe that this approach may allow us to identify patients at risk of developing sepsis earlier than any current method."

• Additional studies using the microfluidic device in a larger group and including a more diverse group of patients are now ongoing at the MGH

In conclusion, the discovery of this microfluidic device with the ability to correctly diagnose/predict sepsis early could be a potential game changer in the management of acutely ill patients with improved patient prognosis and a significant reduction in mortality rates.

About Sepsis In Brief

Sepsis is defined as life-threatening organ dysfunction due to an impaired host response to infection, and is still a leading cause of death in acutely ill patients. It is currently diagnosed based on clinical parameters (which may be subjective), rather than biologic and/or molecular criteria.

Neutrophils have long been known to play a major role in sepsis and studies such as these that enable precise measurement of neutrophil function can greatly improve the diagnostic accuracy of as well as treatment (and prevention) of sepsis.

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References:

1. Ellett F, Jorgensen J, Marand A L,  Liu Y M, Martinez M M, Sein V,  Butler K L,  Lee J &  Irimia D. Diagnosis of sepsis from a drop of blood by measurement of spontaneous neutrophil motility in a microfluidic assay. Nature Biomedical Engineering (2018) doi:10.1038/s41551-018-0208-z

Source-Medindia