Mannose-binding lectin serum levels in neonatal sepsis and septic shock

Severe sepsis and septic shock are a primary cause of death in patients in intensive care unit (ICU). Investigations upon genetic susceptibility profile to systemic complications during severe infections are a field of increasing scientific interest. Particularly when adaptive immune system is compromised or immature, innate immunity plays a key role in the immediate defense against invasive pathogens. Mannose-binding lectin (MBL) is a serum protein that recognizes a wide range of pathogenic microorganisms and activates complement cascade via the antibody-independent pathway. More than 30% of humans harbor mutations in MBL gene (MBL2) resulting in reduced plasmatic levels and activity. Increased risk of infection acquisition has been largely documented in MBL-deficient patients, but the real impact of this form of innate immunosuppression upon clinical outcome is not clear. In critically ill patients higher incidence and worse prognosis of severe sepsis/septic shock appear to be associated with low-producers haplotypes. However an excess of MBL activation might be also harmful due to the possibility of an unbalanced proinflammatory response and an additional host injury. Strategies of replacement therapies in critically ill patients with severe infections are under investigation but still far to be applied in clinical practice.

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Mannose-Binding Lectin in Severe Acute Respiratory Syndrome Coronavirus Infection

The Journal of Infectious Diseases ◽

10.1086/429631 ◽

2005 ◽

Vol 191 (10) ◽

pp. 1697-1704 ◽

Cited By ~ 133

Author(s):

W. K. Eddie Ip ◽

Kwok Hung Chan ◽

Helen K. W. Law ◽

Gloria H. W. Tso ◽

Eric K. P. Kong ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Serum Levels ◽

Mannose Binding Lectin ◽

In Vitro Assays ◽

Calcium Dependent ◽

Control Subjects ◽

Mannose Binding ◽

Carbohydrate Recognition Domains ◽

Binding Lectin

Abstract Little is known about the innate immune response to severe acute respiratory syndrome (SARS) coronavirus (CoV) infection. Mannose-binding lectin (MBL), a key molecule in innate immunity, functions as an ante-antibody before the specific antibody response. Here, we describe a case-control study that included 569 patients with SARS and 1188 control subjects and used in vitro assays to investigate the role that MBL plays in SARS-CoV infection. The distribution of MBL gene polymorphisms was significantly different between patients with SARS and control subjects, with a higher frequency of haplotypes associated with low or deficient serum levels of MBL in patients with SARS than in control subjects. Serum levels of MBL were also significantly lower in patients with SARS than in control subjects. There was, however, no association between MBL genotypes, which are associated with low or deficient serum levels of MBL, and mortality related to SARS. MBL could bind SARS-CoV in a dose- and calcium-dependent and mannan-inhibitable fashion in vitro, suggesting that binding is through the carbohydrate recognition domains of MBL. Furthermore, deposition of complement C4 on SARS-CoV was enhanced by MBL. Inhibition of the infectivity of SARS-CoV by MBL in fetal rhesus kidney cells (FRhK-4) was also observed. These results suggest that MBL contributes to the first-line host defense against SARS-CoV and that MBL deficiency is a susceptibility factor for acquisition of SARS

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