Phenotyping the Immune Response to Trauma: A Multiparametric Systems Immunology Approach*

Seshadri, Anupamaa; Brat, Gabriel; Yorkgitis, Brian K.; Keegan, Joshua; Dolan, James W.; Salim, Ali; Askari, Reza; Lederer, James A.

doi:10.1097/ccm.0000000000002577

Cited by 61 publications

(41 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, in the grey area represented by trauma patients without an overt derangement of physiologic parameters and with a RTS score of 7.84, copeptin was again superior to lactate in predicting major trauma, need for blood transfusion, and hospital admission. Severe trauma is a complex syndrome encompassing physical damages to multiple organs and tissues, and the physiological reactions to them, including neuroendocrine, metabolic, hemocoagulatory, inflammatory, and immune responses [19][20][21][22]. Neuroendocrine response to multiple trauma is complex and far to be completely understood.…”

Section: Discussionmentioning

confidence: 99%

Serum Copeptin levels in the emergency department predict major clinical outcomes in adult trauma patients

et al. 2020

View full text Add to dashboard Cite

Background: Early prognostication in trauma patients is challenging, but particularly important. We wanted to explore the ability of copeptin, the C-terminal fragment of arginine vasopressin, to identify major trauma, defined as Injury Severity Score (ISS) > 15, in a heterogeneous cohort of trauma patients and to compare its performances with lactate. We also evaluated copeptin performance in predicting other clinical outcomes: mortality, hospital admission, blood transfusion, emergency surgery, and Intensive Care Unit (ICU) admission. Methods: This single center, pragmatic, prospective observational study was conducted at Arcispedale Santa Maria Nuova, a level II trauma center in Reggio Emilia, Italy. Copeptin determination was obtained on Emergency Department (ED) arrival, together with venous lactate. Different outcomes were measured including ISS, Revised Trauma Score (RTS), hospital and ICU admission, blood transfusion, emergency surgery, and mortality. Results: One hundred and twenty five adult trauma patients admitted to the ED between June 2017 and March 2018. Copeptin showed a good ability to identify patients with ISS > 15 (AUC 0.819). Similar good performances were recorded also in predicting other outcomes. Copeptin was significantly superior to lactate in identifying patients with ISS > 15 (P 0.0015), and in predicting hospital admission (P 0.0002) and blood transfusion (P 0.016). Comparable results were observed in a subgroup of patients with RTS 7.84. Conclusions: In a heterogeneous group of trauma patients, a single copeptin determination at the time of ED admission proved to be an accurate biomarker, statistically superior to lactate for the identification of major trauma, hospital admission, and blood transfusion, while no statistical difference was observed for ICU admission and emergency surgery. These results, if confirmed, may support a role for copeptin during early management of trauma patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Serum Copeptin levels in the emergency department predict major clinical outcomes in adult trauma patients

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Overall, the cellular translation results in largely balanced pro-inflammatory and anti-inflammatory protective effects mediated by targeted chemotaxis, cytokine release (with the systemic appearance of, for example, IL-6, IL-8, IL-1Ra and IL-10), the generation of reactive oxygen species (ROS), phagocytosis, the formation of neutrophil extracellular traps (NETs) and the killing of bacteria 6,24–28 . The release of microvesicles from leukocytes can also enhance leukocyte adhesion and systemic inflammation and promote activation of the clotting system as a strategy for containing hemorrhage 29,30 .…”

Section: Protective and Harmful Innate Immune Responses To Traumamentioning

confidence: 99%

Innate immune responses to trauma

2018

View full text Add to dashboard Cite

Trauma can affect any individual at any location and at any time over a lifespan. The disruption of macrobarriers and microbarriers induces instant activation of innate immunity. The subsequent complex response, designed to limit further damage and induce healing, also represents a major driver of complications and fatal outcome after injury. This Review aims to provide basic concepts about the posttraumatic response and is focused on the interactive events of innate immunity at frequent sites of injury: the endothelium at large, and sites within the lungs, inside and outside the brain and at the gut barrier.

show abstract

“…(2017) found significantly increased levels of circulating monocytes in trauma patients in the first five days after trauma compared to healthy volunteers. [ 9 ] Conversely, they found a significant depression of monocytic cytokine production (TNF-α, IL-1β) as well as significantly impaired expression of MHC-II molecules on the surface, while the phagocytic capability was not affected over the 5 days post-trauma. [ 9 ] Heftrig et al .…”

Section: Introductionmentioning

confidence: 99%

Early decreased TLR2 expression on monocytes is associated with their reduced phagocytic activity and impaired maturation in a porcine polytrauma model

et al. 2017

View full text Add to dashboard Cite

In their post-traumatic course, trauma patients suffering from multiple injuries have a high risk for immune dysregulation, which may contribute to post-injury complications and late mortality. Monocytes as specific effector cells of the innate immunity play a crucial role in inflammation. Using their Pattern Recognition Receptors (PRRs), notably Toll-Like Receptors (TLR), the monocytes recognize pathogens and/or pathogen-associated molecular patterns (PAMPs) and organize their clearance. TLR2 is the major receptor for particles of gram-positive bacteria, and initiates their phagocytosis. Here, we investigated the phagocytizing capability of monocytes in a long-term porcine severe trauma model (polytrauma, PT) with regard to their TLR2 expression. Polytrauma consisted of femur fracture, unilateral lung contusion, liver laceration, hemorrhagic shock with subsequent resuscitation and surgical fracture fixation. After induction of PT, peripheral blood was withdrawn before (-1 h) and directly after trauma (0 h), as well as 3.5 h, 5.5 h, 24 h and 72 h later. CD14+ monocytes were identified and the expression levels of H(S)LA-DR and TLR2 were investigated by flow cytometry. Additionally, the phagocytizing activity of monocytes by applying S. aureus particles labelled with pHrodo fluorescent reagent was also assessed by flow cytometry. Furthermore, blood samples from 10 healthy pigs were exposed to a TLR2-neutralizing antibody and subsequently to S. aureus particles. Using flow cytometry, phagocytizing activity was determined. P below 0.05 was considered significant. The number of CD14+ monocytes of all circulating leukocytes remained constant during the observational time period, while the percentage of CD14+H(S)LA-DR+ monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of TLR2+ expressing cells out of all monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of phagocytizing monocytes decreased immediately and remained lower during the first 3.5 h after trauma, but increased after 24 h. Antagonizing TLR2 significantly decreased the phagocytizing activity of monocytes. Both, decreased percentage of activated as well as TLR2 expressing monocytes persisted as long as the reduced phagocytosis was observed. Moreover, neutralizing TLR2 led to a reduced capability of phagocytosis as well. Therefore, we assume that reduced TLR2 expression may be responsible for the decreased phagocytizing capacity of circulating monocytes in the early post-traumatic phase.

show abstract

Phenotyping the Immune Response to Trauma: A Multiparametric Systems Immunology Approach*

Cited by 61 publications

References 29 publications

Serum Copeptin levels in the emergency department predict major clinical outcomes in adult trauma patients

Serum Copeptin levels in the emergency department predict major clinical outcomes in adult trauma patients

Innate immune responses to trauma

Early decreased TLR2 expression on monocytes is associated with their reduced phagocytic activity and impaired maturation in a porcine polytrauma model

Contact Info

Product

Resources

About