Plasma proteomics reveals early, broad release of chemokine, cytokine, TNF, and interferon mediators following trauma with delayed increases in a subset of chemokines and cytokines in patients that remain critically ill

Abstract

Severe injury is known to cause a systemic cytokine storm that is associated with adverse outcomes. However, a comprehensive assessment of the time-dependent changes in circulating levels of a broad spectrum of protein immune mediators and soluble immune mediator receptors in severely injured trauma patients remains uncharacterized. To address this knowledge gap, we defined the temporal and outcome-based patterns of 184 known immune mediators and soluble cytokine receptors in the circulation of severely injured patients. Proteomics (aptamer-based assay, SomaLogic, Inc) was performed on plasma samples drawn at 0, 24, and 72 hours (h) from time of admission from 150 trauma patients, a representative subset from the Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock (PAMPer) trial. Patients were categorized into outcome groups including Early Non-Survivors (died within 72 h; ENS; n=38), Non-Resolvers (died after 72 h or required ≥7 days of intensive care; NR; n=78), and Resolvers (survivors that required < 7 days of intensive care; R; n=34), with low Injury Severity Score (ISS) patients from the Tranexamic Acid During Prehospital Transport in Patients at Risk for Hemorrhage After Injury (STAAMP) trial as controls. The major findings include an extensive release of immune mediators and cytokine receptors at time 0h that is more pronounced in ENS and NR patients. There was a selective subset of mediators elevated at 24 and 72 h to a greater degree in NR patients, including multiple cytokines and chemokines not previously described in trauma patients. These findings were validated in a quantitative fashion using mesoscale discovery immunoassays (MSD) from an external validation cohort (VC) of samples from 58 trauma patients matched for R and NR status. This comprehensive longitudinal description of immune mediator patterns associated with trauma outcomes provides a new level of characterization of the immune response that follows severe injury.

Mass spectrometry‐based proteomic applications in dental implants research

“…A common limitation seen in crevicular fluid proteomics is the lack of identification of cytokines, which was often explained by the low absolute abundance of these proteins [12,14]. Targeted approaches may be appropriate for the direct identification of these cytokines, yet DIAbased approaches have also proven to be suited for deeper proteome coverage, especially in cases of high dynamic ranges of protein expression [24,103]. This further emphasizes the need for well-constructed DIA analyses of the crevicular fluid.…”

“…Differentially adhering proteins were predominantly active in blood coagulation, chemokine and cytokine mediated inflammation and plasminogen activation cascade. Protein identification was neither validated nor was protein adherence assessed in vivo [24].…”

Time-Dependent Changes in Proinflammatory Mediators Are Associated With Trauma-Related Venous Thromboembolism

“…Compared with the no-VTE group, VTE patients received significantly more transfusions of red blood cells (8 [5, 13] vs. 9 [7,13], respectively; P = 0.002) and plasma (5 [2, 9] vs. 7 [4,12], respectively; P = 0.001). Furthermore, compared with no-VTE patients, those who developed VTE had significantly fewer ventilator-free (27 [13,29] vs. 23.5 [12,27], P < 0.01), intensive care unit-free (23 [9,27] vs. 16 [5,23], P < 0.001), and hospital-free days (10 [0, 20] vs. 0 [0, 8], P < 0.001). Interestingly, we observed that patients who did not develop VTE had a significantly higher incidence of in-hospital mortality compared with VTE patients, which could be due to the presence of traumatic brain injury.…”

“…Tissue trauma, particularly in the presence of HS, elicits a profound systemic inflammatory response, hallmarked by significant increases in circulating inflammatory mediators with distinct temporal patterns (23). Although past research has demonstrated an augmented proinflammatory response among trauma and HS patients who develop VTE (24), it remains unexplored whether distinct inflammatory mediators are independent predictors of VTE in this population or whether inflammation is directly linked with hypercoagulability.…”

A 3-O-sulfated heparan sulfate dodecasaccharide (12-mer) suppresses thromboinflammation and attenuates early organ injury following trauma and hemorrhagic shock

“…Organ injury and subsequent development of multiple organ dysfunction syndrome (MODS) is a leading cause of morbidity and mortality following major trauma and hemorrhagic shock (T/HS) (1). While the underlying pathogenesis of MODS after traumatic hemorrhage remains poorly understood, pronounced activation of the coagulation and inflammation systems is evident early in the clinical course and is a known mediator of organ injury in the critically ill (2)(3)(4). The vascular endothelium is a key regulator of thromboinflammation through its expression of an extensive network of anticoagulant and anti-adhesive molecules (5).…”