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Altered monocyte and NK cell phenotypes correlate with posttrauma infection

Seshadri, Anupamaa MD; Brat, Gabriel A. MD; Yorkgitis, Brian K. DO; Giangola, Matt MD; Keegan, Joshua BS; Nguyen, Jennifer P. BS; Li, Wei MD; Nakahori, Yasutaka MD; Wada, Takeshi MD; Hauser, Carl MD; Salim, Ali MD; Askari, Reza MD; Lederer, James A. PhD

Journal of Trauma and Acute Care Surgery: August 2019 - Volume 87 - Issue 2 - p 337–341
doi: 10.1097/TA.0000000000002264
AAST 2017 PODIUM
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BACKGROUND Trauma induces a complex immune response, requiring a systems biology approach to capture multicellular changes. Using mass cytometry by time-of-flight (CyTOF), we evaluated time-dependent changes in peripheral blood in trauma patients to identify changes correlated with infection.

METHODS Total leukocytes were prepared via red blood cell lysis using peripheral blood samples from trauma patients with an Injury Severity Score greater than 20 at Days 1, 3, and 5 after injury, and from age- and sex-matched uninjured controls. Cells were stained using a 33-marker immunophenotyping CyTOF panel. Statistics were calculated using one-way analysis of variance with multiple comparisons.

RESULTS The CyTOF staining demonstrated changes in many cell subsets. The mean expression intensity of CD86 on monocytes decreased significantly at all time points after injury. When the patients were stratified based on development of infection, there was a trend to decreased CD86 expression on monocytes of those patients that developed subsequent infection. Based on stratification, we identified significantly increased expression of CD39 on NK cells only in patients that developed an infection.

CONCLUSION This study used a systems biology approach to identify novel changes in circulating immune cell subsets in trauma patients correlating with post-traumatic infection. Decreased expression of CD86, a costimulatory molecule, on monocytes demonstrates that trauma affects the innate system's ability to control T-cell immunity. We also found that CD39 expression on NK cells increased significantly in patients with subsequent infection. CD39 is a protein that generates adenosine, which has immunosuppressive effects on several immune cell types including NK cells. In summary, our results point to pathways that may be central to second-hit infections and further study to delineate these pathways could be key to generating clinical biomarkers or targeted immune therapies for trauma patients.

LEVEL OF EVIDENCE Prognostic study, level II.

From the Department of Surgery, Brigham and Women's Hospital and Harvard Medical School (A.S., B.K.Y., M.G., J.K., J.P.N., W.L., Y.N., T.W., A.S., R.A., J.A.L.); Boston, Massachusetts; Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School (G.A.B. C.H.), Boston, MA.

Submitted: July 14, 2017, Revised: September 25, 2018, Accepted: October 8, 2018, Published online: April 18, 2019.

This article was presented at the 76th Annual Meeting of AAST and Clinical Congress of Acute Care Surgery, September 13–16, 2017, Baltimore, MD.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.jtrauma.com).

Address for Reprints: James A. Lederer, 75 Francis St., Boston, MA 02115; email: jlederer@rics.bwh.harvard.edu.

Online date: April 19, 2019

© 2019 Lippincott Williams & Wilkins, Inc.