Mannose-binding lectin and infection risk in newborns: a systematic review

Abstract

The authors systematically reviewed the literature on mannose-binding lectin (MBL) and infections in newborns to determine whether infection risk is increased in MBL-deficient newborns. All original reports on MBL and infections in newborns were retrieved from Embase, Medline and CENTRAL from 1966 to December 2009. Information extracted from each article included study design, definitions of MBL deficiency and neonatal infection, follow-up period and risk factor analysis. The validity of each study was assessed. Eight prospective cohort studies, including 3166 (range 47-1832) premature or term neonates, were assessed. MBL levels were measured in five studies and MBL2 genotype in six studies. Definitions of MBL deficiency and infection varied. In three out of five phenotypic studies low MBL levels were statistically significantly associated with increased culture-confirmed sepsis rates, also after correction for gestational age or birth weight. In the first study, the median MBL level was decreased in newborns with confirmed sepsis (170 μg/l) compared with newborns without sepsis (1450 μg/l). In two other studies, culture-confirmed sepsis was associated with MBL levels ≤700 μg/l (OR 15.0, 95% CI 1.5 to 151.3) and ≤400 μg/l (OR 3.1), respectively. The remaining two studies investigated various non-culture-confirmed infections. Only one study included the timepoint of clinical suspicion of infection in multivariate analysis. Contradicting results were reported in six MBL2 genotypic studies. Newborns with low MBL levels appear to have culture-confirmed sepsis more frequently than MBL-sufficient newborns. However, the influence of confounding factors was analysed insufficiently. Variant MBL2 genotypes appear to have less influence.

M-ficolin concentrations in cord blood are related to circulating phagocytes and to early-onset sepsis

“…The lectin pathway consists of four soluble pattern-recognition molecules, mannan-binding lectin (MBL) and M-, L-, and H-ficolins, and of the MBL-associated serine proteases, which are able to activate downstream complement compounds (7). MBL deficiency has been extensively investigated and is associated with an increased susceptibility to sepsis (5,8,9). In contrast, very little is known on the role of ficolins in health and disease (7).…”

Recurrent infections in a rheumatoid arthritis patient with a primary immunodeficiency, treated with conventional and biologic disease-modifying anti-rheumatic drugs

“…Historically, the initial identification of MBL deficiency was noted as a common immunodeficiency in children and was confirmed by different studies in pediatric populations [17,18]. There is substantial evidence that MBL deficiency can predispose to severe infections in immunosuppressed individuals or when the adaptive immune defense is not functioning optimally, such as in the early neonatal period or in cancer patients treated with chemotherapy [19,20].…”

Restoration of MBL-deficiency: Redefining the safety, efficacy and viability of MBL-substitution therapy

“…The majority of published data indicate an increased risk of sepsis in MBL deficient neonates (Israels et al, 2010). It is important to mention several methodological differences between these studies that may account for the variation in results observed: Firstly, various definitions of infection were used, ranging from purely clinical diagnosis to culture-proven sepsis, which should be considered gold-standard.…”