Invloed van Mannose-Binding Lectin Polymorfismen op Infectieuze Complicaties bij Traumapatiënten.

Background of the study:

Infection and sepsis are serious complications that occur in up to 10% of trauma patients. Sepsis, bacteremia, (ventilator-associated) pneumonia and surgical site infections seriously hamper recovery, and may eventually lead to death. Resistance to infection is determined by the innate and the acquired immune systems. The innate immune system is the first line of defense against invading microorganisms. The complement system is part of the innate immune system and consists of three pathways: the classic, alternative and the lectin pathway. These are activated through different mechanisms but eventually all lead to activation of the C3 molecule. The central molecule in the lectin pathway is Mannose-Binding Lectin (MBL), a C-type serum lectin that is primarily produced by the liver. Binding of MBL to carbohydrates present on pathogens activates the lectin pathway of complement activation, resulting in opsonization and anti-microbial protection. Three frequently occurring single nucleotide polymorphisms (SNPs) are described in exon 1 of MBL-2 that are associated with abnormal polymerization of the MBL molecule, decreased serum concentrations, and strongly impaired function. Clinical studies have shown that single nucleotide polymorphisms (SNPs) in the MBL2 gene are associated with increased susceptibility to infections, especially in immune-compromised persons. In addition, SNPs in the promoter region and the 5’ untranslated region of the MBL-2 gene reduce the promoter activity and, hence, result in reduced protein levels. Clinical studies indicate that SNPs in MBL-2 are a predisposing factor for infection: for example they (1) increase the chance of infection with Mycoplasma in patients with Primary Antibody Deficiency, (2) increase the risk of developing SARS, (3) enhance the chance of infectious complication in neutropenic oncology patients, and (4) increase the incidence of infection in patients with hematologic malignancy. These and other studies revealed that studying MBL variant alleles is of considerable clinical interest. During treatment, the immune system of trauma patients is often challenged, therefore on optimal immune status is important. Extrapolating from other studies resulted in the following study hypothesis: MBL-deficiency as a result of SNPs in the MBL-2 gene confers a major risk for the development of and mortality from (serious) infectious complications in trauma patients.



Objective of the study:

The aim of this study is to determine to what extent MBL-2 polymorphisms influence the outcome of
Polytrauma patients. Serious (systemic) infections and local infections are the main outcome parameters. The MBLstatus will be measured by determining the MBL2 genotype, serum-MBL concentration, and the serum-MBL activity.



Study design:

Prospective, observational study.



Study population:

All trauma patients (ISS>15) between 18 and 70 years of age.



Primary study parameters/outcome of the study:

1. Bacteremia (BSI);

2. Pneumonia;

3. Systemic Inflammatory Response Syndrome (SIRS);

4. Sepsis;

5. Septic shock.



Secundary study parameters/outcome of the study (if applicable):

1. Death within 3 months;

2. Surgical site infection;

3. Osteitis after osteosynthesis of fractures.

De studiehypothesen zijn:

1. Traumapatiënten (ISS>15) met MBL-deficiëntie als gevolg van een variant MBL2 haplotype hebben een hogere gevoeligheid voor het ontwikkelen van ernstige (infectieuze) systemische complicaties;

2. Traumapatiënten (ISS>15) met MBL-deficiëntie als gevolg van een variant MBL2 haplotype hebben een hogere kans op overlijden als gevolg van (infectieuze) complicaties tijdens een langdurige opname op de Intensive Care Unit.

Not applicable; single venipuncture.

None (observational study).