Early complementopathy after multiple injuries in humans.

Abstract

After severe tissue injury, innate immunity mounts a robust systemic inflammatory response. However, little is known about the immediate impact of multiple trauma on early complement function in humans. In the present study, we hypothesized that multiple trauma results in immediate activation, consumption, and dysfunction of the complement cascade and that the resulting severe "complementopathy" may be associated with morbidity and mortality. Therefore, a prospective multicenter study with 25 healthy volunteers and 40 polytrauma patients (mean injury severity score = 30.3 ± 2.9) was performed. After polytrauma, serum was collected as early as possible at the scene, on admission to the emergency room (ER), and 4, 12, 24, 120, and 240 h post-trauma and analyzed for the complement profile. Complement hemolytic activity (CH-50) was massively reduced within the first 24 h after injury, recovered only 5 days after trauma, and discriminated between lethal and nonlethal 28-day outcome. Serum levels of the complement activation products C3a and C5a were significantly elevated throughout the entire observation period and correlated with the severity of traumatic brain injury and survival. The soluble terminal complement complex SC5b-9 and mannose-binding lectin showed a biphasic response after trauma. Key fluid-phase inhibitors of complement, such as C4b-binding protein and factor I, were significantly diminished early after trauma. The present data indicate an almost synchronical rapid activation and dysfunction of complement, suggesting a trauma-induced complementopathy early after injury. These events may participate in the impairment of the innate immune response observed after severe trauma.

• Authors: Anne-Maud Burk, Myriam Martin, Michael A Flierl, Daniel Rittirsch, Matthias Helm, Lorenz Lampl, Uwe Bruckner, Gregory L Stahl, Anna M Blom, Mario Perl, Florian Gebhard, Markus Huber-Lang
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 37 Issue 4 Pg. 348-54 (Apr 2012) ISSN: 1540-0514 [Electronic] United States
• PMID: 22258234 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Complement C4b-Binding Protein
• Complement Membrane Attack Complex
• Mannose-Binding Lectin
• SC5b-9 protein complex
• Complement C3a
• Complement C5a

Topics

• Complement C3a (metabolism)
• Complement C4b-Binding Protein (metabolism)
• Complement C5a (metabolism)
• Complement Membrane Attack Complex (metabolism)
• Humans
• Mannose-Binding Lectin (blood)
• Multiple Trauma (blood, immunology, metabolism)
• Prospective Studies