Trauma-Induced Long-Term Alterations of Human T Cells and Monocytes—Results of an Explorative, Cross-Sectional Study. Issue 1 (January 2020)

• Record Type: Journal Article
• Authors: Ruhrmann, Sophie; Schneck, Emmanuel; Markmann, Melanie; Zink, Jan; Zajonz, Thomas Simon; Arens, Christoph; Uhle, Florian; Sander, Michael; Koch, Christian
• Is Part Of: Shock. Volume 53:Issue 1(2020)
• Publication Date: 2020-01
• Subjects: CARS -- immune tolerance -- inflammation -- multiple trauma -- SIRS -- Abbreviations -- APC -- allophycocyan -- BTLA -- B- and T-lymphocyte attenuator -- CARS -- compensatory anti-inflammatory response syndrome -- CD -- cluster of differentiation -- CRP -- C-reactive protein -- CTLA-4 -- cytotoxic T-lymphocyte-associated protein 4 -- CTRL -- control -- DAMP -- damage-associated patterns -- EDTA -- ethylenediaminetetraacetic acid -- FITC -- fluorescin isothiocyanate -- HLA-DR -- human leucocyte antigen D-related receptor -- IL -- interleukin -- INF -- interferon -- ISS -- injury severity score -- LPS -- lipopolysaccharide -- MODS -- multiple organ dysfunction syndrome -- PCT -- procalcitonin -- PD 1 -- programmed cell death protein 1 -- PD-1 L -- programmed death ligand 1 -- PDMS -- patient data management system -- PE -- phycoerythrin -- PICS -- persistent inflammation, immunosuppression and catabolism syndrome -- RAGE -- receptors for advanced glycation end products -- SIRS -- systemic inflammatory response syndrome -- TLR -- toll-like receptor -- TNF -- tumor necrosis factor; Shock -- Periodicals; Shock -- Periodicals; Choc (Pathologie) -- Périodiques; Shock; Periodicals; 616.0475
• DOI: 10.1097/SHK.0000000000001358
• Languages: English
• ISSNs: 1073-2322

Abstract

ABSTRACT: Background: Major trauma leads to complex immune reactions, known to result in a transient immunodeficiency. The long-term consequences of severe trauma on immune function and regulation as well as its clinical impact remain unclear. Methods: Six months (ranging from −12 to +5 days) after a major trauma event, 12 former trauma patients (Injury Severity Score ≥ 16) and 12 healthy volunteers were enrolled. The current clinical status and infection history since discharge were assessed by a standardized questionnaire. Immune cell subsets (cluster of differentiation (CD)4 +, CD8 +, CD14 + ), cell surface receptor expression (programmed cell death protein 1 (PD-1), B- and T-lymphocyte attenuator (BTLA), cytotoxic T-lymphocyte-associated protein 4, toll-like receptor (TLR)-2, -4, and -5, Dectin-1, programmed death ligand 1 (PD-1L)), and human leucocyte antigen D-related receptor (HLA-DR)-expression were quantified by flow cytometry. Cytokine secretion (IL-2, -4, -6, -10, and 17A, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ) was assessed after stimulation of whole blood with LPS-, α-CD3/28, or zymosan. Results: Analysis of surface receptors on T cells revealed a significant elevation of PD-1 expression on CD4 + T cells, whereas BTLA expression on CD4 + and CD8 + T cells was significantly suppressed in the trauma cohort. Monocytes showed a significantly reduced expression of TLR-2 and -4 as well as a reduced proportion of TLR-4 monocytes. HLA-DR receptor density revealed no significant changes between both cohorts. LPS-induced IL-6 and TNF-α secretion showed non-significant trends toward reduced values. No differences regarding clinical apparent infections could be detected. Conclusions: Six months following major trauma, changes of cell surface receptors on CD4 + and CD8 + T cells as well as on CD14 + monocytes were present, hinting toward an immunosuppressive phenotype. Following major trauma, although IL-6 and TNF-α release after stimulation were reduced, they did not reach statistical significance. Overall, further studies are necessary to evaluate the clinical implications of these findings. Trial registration: DRKS00009876, Internet Portal of the German Clinical Trials Register (DRKS), registration date 11.08.2016, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00009876 . Abstract : Supplemental Digital Content is available in the text