Early Complementopathy After Multiple Injuries in Humans.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

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 [ISS] = 30.3 ± 2.9) was performed. After polytrauma serum was collected as early as possible at the scene, upon admission to the emergency room and 4, 12, 24, 120 and 240 hours post trauma and analysed 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 non-lethal 28-day outcome. Serum levels of the complement activation products C3a and C5a were significantly elevated throughout the entire observation period and correlatedwith the severity of traumatic brain injury and survival. The soluble terminal complement complex SC5b-9 and mannose-binding lectin (MBL) showed a biphasic response after trauma. Key fluid phase inhibitors of complement, such as C4b-binding protein (C4BP) and factor I, were significantly diminished early after trauma.The present data indicate an almost synchronically rapid activation and dysfunction of complement suggesting a trauma-induced "complementopathy" early after injury. These events may participate to the impairment of the innate immune response observed after severe trauma.

Detaljer

Författare
  • Anne-Maud Burk
  • Myriam Martin
  • Michael A Flierl
  • Daniel Rittirsch
  • Matthias Helm
  • Lorenz Lampl
  • Uwe Bruckner
  • Gregory L Stahl
  • Anna Blom
  • Mario Perl
  • Florian Gebhard
  • Markus Huber-Lang
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Annan medicinsk grundvetenskap
Originalspråkengelska
Sidor (från-till)348-354
TidskriftShock
Volym37
Utgivningsnummer4
StatusPublished - 2012
PublikationskategoriForskning
Peer review utfördJa