Influence of Mannose-Binding Lectin Polymorphisms on Infectious Complications in Trauma Patients

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.

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

Prospective, observational study.

The risk for the patients is limited to a single withdrawal of 2 tubes of blood
(10 ml each). This will preferably be done at the time of routine blood
sampling. If that is not possible, one venipuncture will be performed. The risk
of this venipuncture is slight, and the total duration of the examination will
take 10 minutes at the most.