MANNOSE-BINDING LECTIN AND L-FICOLIN POLYMORPHISM IN PATIENTS WITH STAPHYLOCOCCAL BACTEREMIA

Blood stream infections with gram-positive bacteria, especially Staphylococcus
Aureus (S. aureus), are associated with significant morbidity and mortality,
resulting in considerable health care costs. Gram-positive bacteremia is
relatively common in patients with mediastinitis following cardiothoracic
surgery, in patients with endocarditis and in neutropenic patients who received
high dose chemotherapy.
Mannose-binding lectin (MBL) and L-ficolin (FCN) are activators of the lectin
pathway of complement and are crucial components of the innate immune defence
against infection. Single-nucleotide polymorphisms (SNPs) in the MBL and FCN
genes, which are common in the general population, influence the functionality
of these pathways. Recent data from the research group in the Medical
Microbiology & Immunology (MMI) laboratory has indicated that both MBL and FCN
are capable of binding directly to gram-positive bacteria.
In a joined project of the departments of MMI, Internal Medicine and
Pulmonology the role of MBL and FCN in patients with community acquired
pneumonia (CAP) has been investigated. We showed that MBL can act as a acute
phase protein and that this acute phase responsiveness is highly dependent upon
the MBL genotype. In addition we recently showed that CAPD (continuous
ambulatory peritoneal dialysis) patients with FCN genotypes coding for FCN
deficient staphylococcal binding, had an increased risk of developing
peritonitis with gram positive bacteria. We were able to show genetic
differences in a study of 40 cases and 60 controls. The relatively low number
of cases needed to show genetic differences points at the major role of FCN in
the defence against CAPD related peritonitis caused by gram-positive
micro-organisms.
We hypothesize that polymorphisms in the genes encoding for MBL and FCN also
increase the risk of gram-positive bacteremia in patients following
cardiothoracic surgery, in patients with endocarditis and in neutropenic
patients who received high dose chemotherapy.
Furthermore we want to study whether extracorporeal circuits, used in
cardiothoracic surgery, and high dose chemotherapy influence the circulating
levels of MBL and FCN, thereby potentially increasing the risk of infection.

To determine the frequency of MBL and FCN SNPs in patients with a history of a
proven gram-positive bacteremia, compared to patients without such history. A
secondary objective is to determine whether extracorporeal circuits, used in
cardiothoracic surgery, and high dose chemotherapy influence circulating levels
of MBL and FCN.

The main study consists of three separate case-control studies. These studies
are observational, mono-centre, retrospective studies.
In the sub-study the primary goal is to study the effect of extracorporeal
circuits and high dose chemotherapy on the circulating levels of MBL and FCN.
This is a small, observational, prospective cohort study.

From all patients who agree to participate, one or two (only in the sub-study)
blood samples will be drawn. When patients are admitted (as will be the case
for all sub-study patients), this will be combined with regular diagnostic
blood sampling, so no extra venipuncture is necessary for these patients.
Alternatively, a blood sample can be obtained when patients visit the
outpatient department for regular check-up and blood sampling. If patients are
deceased or when they don*t visit the hospital regularly, sampled tissue or
stored blood serum is often available and can be used to measure MBL and FCN
polymorphisms. Therefore, the risks associated with participation can be
considered negligible and the burden can be considered minimal.