Doctors Link Pathogenic Neutrophil Protein to Increased Septic Shock Complications

Published April 2017
Critical Care Medicine

Until recently, doctors assumed that neutrophils—the most abundant of the body’s leukocytes and the first line of response to infection—were fairly homogenous and presented the same throughout the body.

But new findings from the Division of Critical Care Medicine indicate that a pathogenic neutrophil subset and an associated protein appear to be far more prevalent in patients with septic shock compared to healthy controls.

“We found evidence that suggests there is a subset of neutrophils in patients who present with septic shock, a subset that expresses the olfacotmedin-4 (OLMF4) protein,” says Matthew Alder, MD, PhD, who co-authored the study with Hector Wong, MD, director of the Division of Critical Care Medicine. “The more of these subset neutrophils a patient has, the worse the prognosis.”

The study examined outcomes involving 41 patients with septic shock compared to a 29-patient pediatric ICU control group and 33 healthy controls. Among patients who died of septic shock, serum protein concentrations of the up-regulated olfactomedin-4 protein were nearly 100 times higher than among healthy controls. Patients with higher levels of the pathogenic neutrophils also were far more likely to experience organ failures.

Researchers are continuing to investigate these subsets of neutrophils in the body. They seek to confirm whether OLFM4 is a marker of cellular damage and whether it can be used as a marker for septic shock diagnosis.

The percentage of olfactomedin-4 (OLFM4)+ neutrophils is higher in those patients with complicated course. The boxed data in the left figure depicts flow cytometric analysis of leukocytes from a patient with septic shock. The boxed data in the right figure shows CD66b positive neutrophils, and the percentage of those neutrophils that express OLFM4.

Click image to enlarge.

The percentage of OLFM4+ neutrophils is not significantly different between healthy controls, intensive care controls, or patients with septic shock (B). When comparing just patients with septic shock, those with a complicated course had a higher percentage OLFM4+ cells when compared with non-complicated course (C).

Click image to enlarge.

Citation

Alder MN, Opoka AM, Lahni P, Hildeman DA, Wong HR. Olfactomedin-4 Is a Candidate Marker for a Pathogenic Neutrophil Subset in Septic Shock. Crit Care Med. 2017 Apr;45(4):e426-e432.

Matthew Alder, MD, PhD