Mannose Binding Lectin Acute Phase Activity in Patients with Severe Infection

Abstract

Mannose Binding Lectin (MBL) is a liver derived, circulating plasma protein that plays a pivotal role in innate immunity. MBL functions as a pathogen recognition molecule, opsonising organisms and initiating the complement cascade. MBL deficiency arising from mutations and promoter polymorphisms in the MBL2 gene is common and has been associated with risk, severity, and frequency of infection in a number of clinical settings. With MBL therapy on the horizon, the usefulness of replacement MBL therapy has been challenged by the notion, that as an acute phase protein, MBL levels may rise under stress to sufficient levels, in individuals who are usually deficient. This report demonstrates that in patients with sepsis and septic shock, the majority of patients do not display an MBL acute phase response: 41.4% of individuals maintained consistent MBL levels throughout hospital stay, 31.3% of individuals demonstrated a positive acute phase response, and a negative acute phase response was observed in 27.3% of individuals studied. Importantly, a positive acute phase response was generally observed in individuals with wild-type MBL2 genes. When a positive acute phase response was observed in individuals with coding mutation, these individuals demonstrated a normal MBL level on admission to hospital. Furthermore, no individual, regardless of genotype who was MBL deficient at admission was able to demonstrate a positive acute phase response into the normal MBL range. These findings indicate MBL demonstrates a variable acute phase response in the clinical setting of sepsis and septic shock.

Mannose-Binding Lectin Deficiency Facilitates AbdominalCandidaInfections in Patients with Secondary Peritonitis

“…There was an increased susceptibility to infections in chemotherapy patients with MBL levels of 0.5 g/ml or less (35). Also, sepsis patients with baseline MBL deficiencies failed to produce MBL at levels greater than 0.5 g/ml (8).…”

Association of polymorphisms in the mannose-binding lectin gene and pulmonary morbidity in preterm infants

“…3,[7][8][9][10] Especially in immunocompromised individuals, MBL deficiency appears to exert effects on susceptibility and severity of infectious diseases. [11][12][13][14][15][16] Because their adaptive immunity has not yet been developed, MBL is particularly important in neonates in whom immune defense depends on maternal antibodies and innate defense mechanisms. The ability to respond effectively to infectious hazards clearly determines acute and long-term outcome especially in preterm infants.…”

Distinct Longitudinal Associations of MBL, MASP-1, MASP-2, MASP-3, and MAp44 With Endothelial Dysfunction and Intima–Media Thickness

“…Interestingly, the association between MBL and low-grade inflammation was not linear because high MBL also tended to be associated with more low-grade inflammation. Because MBL is a weak acute phase-reactant, 28,29 we tested whether this finding might be driven by participants with elevated CRP concentrations indicative of acute inflammation. This was not the case, as upon exclusion of participants with elevated CRP, these associations were actually considerably strengthened: both low and high MBL concentrations were significantly associated with more low-grade inflammation, indicating a potentially U-shaped association.…”