Genotypes Coding for Low Serum Levels of Mannose-Binding Lectin Are Underrepresented among Individuals Suffering from Noninfectious Systemic Inflammatory Response Syndrome

Gene polymorphisms, giving rise to low serum levels of mannose-binding lectin (MBL) or MBL-associated protease 2 (MASP2), have been associated with an increased risk of infections. The objective of this study was to assess the outcome of intensive care unit (ICU) patients with systemic inflammatory response syndrome (SIRS) regarding the existence of functionally relevant MBL2 and MASP2 gene polymorphisms. The study included 243 ICU patients with SIRS admitted to our hospital, as well as 104 healthy control subjects. MBL2 and MASP2 single nucleotide polymorphisms were genotyped using a sequence-based typing technique. No differences were observed regarding the frequencies of low-MBL genotypes (O/O and XA/O) and MASP2 polymorphisms between patients with SIRS and healthy controls. Interestingly, ICU patients with a noninfectious SIRS had a lower frequency for low-MBL genotypes and a higher frequency for high-MBL genotypes (A/A and A/XA) than either ICU patients with an infectious SIRS or healthy controls. The existence of low- or / high-MBL genotypes or a MASP2 polymorphism had no impact on the mortality rates of the included patients. The presence of high-MBL-producing genotypes in patients with a noninfectious insult is a risk factor for SIRS and ICU admission. Sepsis is the main cause of death in intensive care units (ICU), with mortality rates above 50% in patients with septic shock (54). Increasing evidence suggests that variations in genes encoding different components of the immune system influence an individual’s capacity to respond adequately to infections. Genetic polymorphisms of several molecules of the innate immune system, such as tumor necrosis factor alpha (TNF-) (35), interleukin-1 receptor antagonist (IL-1RA) (2), and more recently plasminogen activator inhibitor 1 (PAI-1) (12), have been associated with increased mortality in patients with severe sepsis and septic shock. The mannose-binding lectin (MBL) is an important element of the innate immune defense system. The MBL is a circulating C-type plasma lectin, mainly produced by the liver, which binds to the specific carbohydrates present on the surface of different microorganisms (21, 38). In serum, MBL is present as oligomers (mainly trimers and tetramers) bound to the MBL-associated serine proteases (MASPs, which are also produced in the liver), mainly MASP2. Once bound to the carbohydrate residues, the MBL/MASP2 complex acts as an opsonin for phagocytosis for numerous pathogens and activates comple