Low mannose-binding lectin function is associated with sepsis in adult patients

Abstract

Mannose-binding lectin (MBL) is an innate immune system pattern recognition molecule that kills a wide range of pathogens via the lectin complement pathway. MBL deficiency is associated with severe infection but the best measure of this deficiency is undecided. We investigated the influence of MBL functional deficiency on the development of sepsis in 195 adult patients, 166 of whom had bloodstream infection and 35 had pneumonia. Results were compared with 236 blood donor controls. MBL function (C4b deposition) and levels were measured by enzyme-linked immunosorbent assay. Using receiver-operator characteristics of MBL function in healthy controls, we identified a level of <0.2 U microL(-1) as a highly discriminative marker of low MBL2 genotypes. Median MBL function was lower in sepsis patients (0.18 U microL(-1)) than in controls (0.48 U microL(-1), P<0.001). MBL functional deficiency was more common in sepsis patients than controls (P<0.001). MBL functional deficient patients had significantly higher sequential organ failure assessment (SOFA) scores and higher MBL function and levels were found in patients with SOFA scores predictive of good outcome. Deficiency of MBL function appears to be associated with bloodstream infection and the development of septic shock. High MBL levels may be protective against severe sepsis.

Levels of mannose-binding lectin in individuals with visceral leishmaniasis in the northeast region of Brazil

“…MBL deficiency (serum concentration below 100 ng/mL) is associated with severity and susceptibility to infectious diseases (Eisen et al, 2006). However, high MBL concentrations may favor infection by some intracellular parasites such as Leishmania, which uses C3 opsonization and its receptor to enter the host cells (Garred et al,1994).Thus, mechanisms that decrease complement activation may hinder the entry of the parasites into the cells (Santosetal., 2001;Bonar et al, 2004).…”

“…The importance of MBL protein in innate immunity has been shown by studies that associate deficiency of MBL with susceptibility to several infectious diseases, mainly extracellular pathogens, and particularly the microorganisms that cause acute infection in childhood (Garred et al,1995;Garred et al, 1997;Koch et al, 2001;Eisen et al, 2006). Conversely, some evidence suggests that there is a direct association between MBL levels and the risk of infection by some intracellular parasites such as Leishmania, although as yet there is no scientific consensus.…”

“…The association between MBL and human diseases has been investigated in recent years because of the increasing evidence that correlates genetic variation and susceptibility to some types of infections and autoimmune, metabolic, and cardiovascular diseases (Rector et al, 2001;Roy et al, 2002;Seibold et al, 2004;Fidler et al, 2004;Eisen et al, 2006;Garred et al, 2006;Eisen et al, 2008).…”

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.…”

Association of lectin pathway proteins with intra-abdominal Candida infection in high-risk surgical intensive-care unit patients. A prospective cohort study within the fungal infection network of Switzerland

“…Quantification of MBL plasma levels was performed using a mannan-binding enzyme-linked immunosorbent assay as previously described (27,28). Briefly, mannan-coated microtitre plates were incubated with samples at 1:25 and 1:100 dilutions for 90 min at room temperature followed by detection of bound MBL with a biotinylated monoclonal anti-MBL antibody (HYB 131-01, BioPorto Diagnostics, Denmark).…”