UC San Diego

Background

We identified recently esophageal cancer related gene-4 (ECRG4) as a candidate cytokine that is expressed on the surface of quiescent polymorphonuclear leukocytes (PMNs) and shed in response to ex vivo treatment with lipopolysaccharide. To investigate the potential biologic relevance of changes in cell surface ECRG4 in human samples, we performed a pilot study to examine a population of burn patients in whom blood could be analyzed prospectively. We hypothesized that cutaneous burn injury would alter cell surface expression of ECRG4 on PMNs.

Methods

Patients admitted with more than 20% total burn surface area (TBSA) (n = 10) had blood collected at the time of admission and weekly thereafter. For comparison, blood was obtained from a control group of healthy human volunteers (n = 4). We used flow cytometry to measure changes in ECRG4(+) PMNs from patients during recovery from injury. Esophageal cancer related gene-4 expression at each time point was compared with the patient's clinical status based on a Multiple Organ Dysfunction (MOD) score.

Results

Esophageal cancer related gene-4 was detected on the PMN surface of cells collected from healthy volunteers, however, within 48 h of admission after burn injury (n = 10 patients), the number of PMNs with cell surface ECRG4 was decreased. Esophageal cancer related gene-4 expression in PMNs was re-established over the course of patient recovery, unless complications occurred. In this case, the decrease in cell surface ECRG4(+) PMNs preceded the clinical diagnosis of infectious complications and was reflected by increased organ injury scores.

Conclusion

From a small sample set, we were able to determine that PMN cell surface ECRG4 expression was decreased after burn injury and returned to baseline during recovery from injury. Although larger studies are needed to define the role of ECRG4 in human PMNs further, this report is the first assessment of cell surface ECRG4 protein in a patient population to support analogous findings in animal studies.