Effect of Severe Trauma on PD1 and Its Legend (PD1/L1) on T Lymphocytes and Correlation With Mortality

Unlike neuro-endocrine response to trauma; posttraumatic immune alterations are not easily carried out at bedside. The majority of trials were conducted in the intensive care usually hours to days post injury.

In this trial the investigators sought assess the immune responses during emergency department trauma resuscitation by looking at the biomarkers of severe injury by comparing T lymphocytes and programmed cell death molecules and its relation with mortality.

Trauma is a major healthcare problem with a high mortality rate that might be caused by immune-suppression.

Trauma initiates an immunosuppressive response which is contributor tocell damage and could be a marker of multi organ failure and mortality.

Programmed cell death receptor-1 (PD-1) and programmed cell death receptor ligand-1 (PD-L1), which are co-inhibitory receptor molecules, may participate in trauma-induced immune-suppression.

Both sterile and infected trauma induce the systemic inflammatory response syndrome (SIRS), originally defined by pyrexia, tachycardia, hyperventilation and neutrophilia, the latter responding poorly to pathogens. (10) Accompanying these changes is a decrease in circulating basophil, eosinophil and natural killer precursors, which further weakens systemic immunity.

Apoptosis (Programmed Cell Death):

Programmed cell-death (PCD) is death of a cell in any form, mediated by an intracellular program. PCD is carried out in a regulated process, which usually confers advantage during an organism's life-cycle. Apoptosis and autophagy are both forms of PCD, but necrosis is a non-physiological process that occurs as a result of infection or injury.

Programmed cell death protein 1 Programmed cell death protein 1, also known as PD-1 and CD 279 (cluster of differentiation 279), is a protein that in humans is encoded by the PDCD1 gene. PD-1 is a cell surface receptor that belongs to the immunoglobulin super family and is expressed on T cells and pro-B cells. PD-1 binds two ligands, PD-L1 and PD-L2. PD-1, functioning as an immune checkpoint, plays an important role in down regulating the immune system by preventing the activation of T-cells, which in turn reduces autoimmunity and promotes self-tolerance.

Ligands PD-1 has two ligands, PD-L1 and PD-L2, which are members of the B7 family. Several lines of evidence suggest that PD-1 and its ligands negatively regulate immune responses PD-1 knockout mice have been shown to develop lupus-like glomerulo-nephritis and dilated cardiomyopathy Triggering PD-1, expressed on monocytes and up-regulated upon monocytes activation, by its ligand PD-L1 induces IL-10 production which inhibits CD4 T-cell function.

Eligibility Criteria:
Inclusion Criteria:

1. Adult trauma patients with blunt or penetrating injury.
2. Major injury:

   * Injury severity score \> 15
   * Drop in hematocrit \> 10 points
   * Transfusion of more than 6-10 units of packed RBCs
   * Serum lactate \> 3 mmol/L
3. Mean arterial blood pressure ≤ 60 mmHg and/or systolic arterial blood pressure ≤ 90 mmHg.
4. Patients admitted to the ED within 6 hours after the onset of trauma

Exclusion Criteria:

- 1. age less than 18 years; 2. patients who died within 2 days of the onset of trauma; 3. patients who declined to consent; 4. Known pregnancy. 5. Patients with limb ischemia or peripheral vascular occlusion. 6. Patients admitted to the emergency trauma department after 6 hours of the trauma event.

7. Preexisting conditions as severe cardiovascular disease, uncontrolled hemorrhage.