Abstract

Polymorphisms of various immune defence genes interfere with the risk of severe infections in critically ill patients. This includes studies on autologous and allogeneic stem cell transplantation (ASCT).

Mannan-binding lectin (MBL) is a plasma protein which is able to recognize carbohydrate structures forming pathogen associated molecular patterns on the surface of bacteria and viruses. When binding to pathogens occur the complement system is activated leading killing of the microorganisms. Lack of MBL may lower the ability to resist infections.

The gene MBL2, encoding mannan-binding lectin (MBL), contains three well-characterized single nucleotide polymorphisms B (G54D), C (G57E), and D (R52C) (collectively termed O in contrast to the wild-type A). The presence of O variants greatly reduces the effector functions of MBL.

We examined the impact of the polymorphisms on the occurrence of severe infections related to ASCT in patients with multiple myeloma. Patients were genotyped with PCR techniques using aliquots of peripheral stem cells from apheresis. Infectious complications were recorded retrospectively from clinical records and database extractions from the Department of Microbiology. One hundred and thirteen consecutive patients were studied. During ASCT 71 patients (63%) had fever above 38.5°C despite prophylactic antibiotics. Eleven (10%) patients had proven sepsis. MBL2 analyses: 4/71 patients with AA genotype had sepsis versus 7/41 with AO/OO genotype (p=0.09). Two lethal cases of sepsis were seen in the AO/OO patients, none in the AA patients. In multivariate analyses the risk of sepsis was significantly lower in AA patients: OR 0.15 (95% CI: 0.03–0.74), p=0.02. Wild-type MBL2, associated with a high function of mannose-binding lectin, probably reduces the risk of sepsis in myeloma patients during ASCT. Myeloma patients with variant MBL2 may be candidates for future MBL replacement trials.

Disclosures: Steffen Thiel has been a consultant for the start-up company NatImmune A/S, Copenhagen, Denmark.; Steffen Thiel owns stocks in a start-up company, NatImmune A/S, Copenhagen, Denmark. The company explores the possibility of using mannan-binding lectin as a therapeutic drug.

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