Complement After Trauma: Suturing Innate and Adaptive Immunity

Chakraborty, Shinjini; Karasu, Ebru; Huber‐Lang, Markus

doi:10.3389/fimmu.2018.02050

Cited by 34 publications

(37 citation statements)

References 178 publications

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“…It can be speculated that maybe upon reduced TAFI levels, missing inactivation of C3a and C5a may lead to an immunological imbalance and an excessive immunological reaction. As nicely reviewed and originally published by the expert group around Huber-Lang, anaphylatoxin C5a appears in the circulation of humans within 20 min post-polytrauma, and its levels have been related to the mortality rate [31,32]. That data indicated an almost synchronical rapid activation and dysfunction of the complement, suggesting a trauma-induced complementopathy early after injury [32].…”

Section: Discussionmentioning

confidence: 95%

Post-Traumatic Sepsis Is Associated with Increased C5a and Decreased TAFI Levels

Vollrath

Marzi

Herminghaus

et al. 2020

JCM

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Background: Sepsis frequently occurs after major trauma and is closely associated with dysregulations in the inflammatory/complement and coagulation system. Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a dual role as an anti-fibrinolytic and anti-inflammatory factor by downregulating complement anaphylatoxin C5a. The purpose of this study was to investigate the association between TAFI and C5a levels and the development of post-traumatic sepsis. Furthermore, the predictive potential of both TAFI and C5a to indicate sepsis occurrence in polytraumatized patients was assessed. Methods: Upon admission to the emergency department (ED) and daily for the subsequent ten days, circulating levels of TAFI and C5a were determined in 48 severely injured trauma patients (injury severity score (ISS) ≥ 16). Frequency matching according to the ISS in septic vs. non-septic patients was performed. Trauma and physiologic characteristics, as well as outcomes, were assessed. Statistical correlation analyses and cut-off values for predicting sepsis were calculated. Results: Fourteen patients developed sepsis, while 34 patients did not show any signs of sepsis (no sepsis). Overall injury severity, as well as demographic parameters, were comparable between both groups (ISS: 25.78 ± 2.36 no sepsis vs. 23.46 ± 2.79 sepsis). Septic patients had significantly increased C5a levels (21.62 ± 3.14 vs. 13.40 ± 1.29 ng/mL; p < 0.05) and reduced TAFI levels upon admission to the ED (40,951 ± 5637 vs. 61,865 ± 4370 ng/mL; p < 0.05) compared to the no sepsis group. Negative correlations between TAFI and C5a (p = 0.0104) and TAFI and lactate (p = 0.0423) and positive correlations between C5a and lactate (p = 0.0173), as well as C5a and the respiratory rate (p = 0.0266), were found. In addition, correlation analyses of both TAFI and C5a with the sequential (sepsis-related) organ failure assessment (SOFA) score have confirmed their potential as early sepsis biomarkers. Cut-off values for predicting sepsis were 54,857 ng/mL for TAFI with an area under the curve (AUC) of 0.7550 (p = 0.032) and 17 ng/mL for C5a with an AUC of 0.7286 (p = 0.034). Conclusion: The development of sepsis is associated with early decreased TAFI and increased C5a levels after major trauma. Both elevated C5a and decreased TAFI may serve as promising predictive factors for the development of sepsis after polytrauma.

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Section: Discussionmentioning

confidence: 95%

Post-Traumatic Sepsis Is Associated with Increased C5a and Decreased TAFI Levels

Vollrath

Marzi

Herminghaus

et al. 2020

JCM

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“…Excessive complement activation after major trauma triggers SIRS that leads to MODS and death. Recently, multiple preclinical and clinical studies have demonstrated that complement activation after major trauma plays critical role in contributing to the SIRS and MODS in traumatic brain injury, chest trauma, musculoskeletal trauma, and polytrauma 28–31. Taken together, the complement activation products represent the main drivers of the systemic inflammation after trauma.…”

Section: Discussionmentioning

confidence: 99%

Early complementopathy predicts the outcomes of patients with trauma

Zhao

Liu

et al. 2019

Trauma Surg Acute Care Open

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BackgroundComplementopathy (rapid complement activation and consumption after trauma) has been reported in trauma patients, but the underlying mechanism of these phenomena and their clinical significance remain unclear. This study aimed to determine the complement/complement pathway activation and identify the association of complement activation with clinical outcomes in trauma patients.MethodsWe studied 33 trauma patients with mean Injury Severity Score of 25, and 25 healthy volunteers. Sera were collected on patients’ arrival at the emergency department, as well as 1, 2, 3, 5, and 7 days after trauma, to measure the levels of terminal complement activation product soluble C5b-9 (sC5b-9) by ELISA. In addition, the functional complement activation pathway was evaluated using a commercial complement system screening kit.ResultsSerum concentrations of sC5b-9 (complement terminal pathway activity) were significantly increased in trauma patients throughout the entire observation period except on day 1. Complement terminal activities were significantly higher in 27 of 33 patients with systemic inflammatory response syndrome (SIRS) than non-SIRS patients on day 2, day 5, and day 7. Increased serum levels of sC5b-9 positively correlated with SIRS. Functional complement analysis revealed that the classical pathway was the predominant pathway responsible for complement activation. Burn patients tended to have a greater and prolonged classical pathway activation than non-burn patients, and burn injury and blunt injury were associated with higher blood levels of sC5b-9 than penetrating injury.DiscussionEarly complement activation through the classical pathway after trauma is observed and positively correlated with the development of SIRS. Thus, monitoring of the complement system might be beneficial in the care of critically injured patients.Level of evidenceIII.Study typePrognostic.

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Section: Complement Factorsmentioning

confidence: 97%

“…Exposure to traumatic or infectious insults results in an immediate activation of the complement cascade as major fluid defense system of innate immunity [48,299]. As nicely described by Huber-Lang, the complement system acts as a master alarm system during the molecular danger response after trauma and significantly contributes to the clearance of DAMPs and PAMPs [48,299]. Activation of complement in trauma patients has been verified by detection of elevated plasma C3a, C5a, and C5b-9 levels which correlate with disease severity [73,[300][301][302][303][304][305].…”

Section: Complement Factorsmentioning

confidence: 99%

Damage-associated molecular patterns in trauma

Relja

Land

2019

Eur J Trauma Emerg Surg

131

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In 1994, the "danger model" argued that adaptive immune responses are driven rather by molecules released upon tissue damage than by the recognition of "strange" molecules. Thus, an alternative to the "self versus non-self recognition model" has been provided. The model, which suggests that the immune system discriminates dangerous from safe molecules, has established the basis for the future designation of damage-associated molecular patterns (DAMPs), a term that was coined by Walter G. Land, Seong, and Matzinger. The pathological importance of DAMPs is barely somewhere else evident as in the posttraumatic or post-surgical inflammation and regeneration. Since DAMPs have been identified to trigger specific immune responses and inflammation, which is not necessarily detrimental but also regenerative, it still remains difficult to describe their "friend or foe" role in the posttraumatic immunogenicity and healing process. DAMPs can be used as biomarkers to indicate and/or to monitor a disease or injury severity, but they also may serve as clinically applicable parameters for optimized indication of the timing for, i.e., secondary surgeries. While experimental studies allow the detection of these biomarkers on different levels including cellular, tissue, and circulatory milieu, this is not always easily transferable to the human situation. Thus, in this review, we focus on the recent literature dealing with the pathophysiological importance of DAMPs after traumatic injury. Since dysregulated inflammation in traumatized patients always implies disturbed resolution of inflammation, so-called model of suppressing/inhibiting inducible DAMPs (SAMPs) will be very briefly introduced. Thus, an update on this topic in the field of trauma will be provided.

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Complement After Trauma: Suturing Innate and Adaptive Immunity

Cited by 34 publications

References 178 publications

Post-Traumatic Sepsis Is Associated with Increased C5a and Decreased TAFI Levels

Post-Traumatic Sepsis Is Associated with Increased C5a and Decreased TAFI Levels

Early complementopathy predicts the outcomes of patients with trauma

Damage-associated molecular patterns in trauma

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