BACKGROUND: Critically ill children are susceptible to nosocomial infections, which contribute to adverse outcomes. Deficiencies in the innate immunity lectin pathway of complement activation are implicated in a child's vulnerability to infections in conditions such as cancer, but the role during critical illness remains unclear. We hypothesized that low on-admission levels of the pathway proteins are, in part, genetically determined and associated with susceptibility to infectious complications and adverse outcomes. METHODS: We studied protein levels of mannose-binding lectin (MBL), H-ficolin and M-ficolin, three MBL-associated-serine proteases (MASPs) and MBL-associated protein (MAp44), and relation with functional genetic polymorphisms, in 130 healthy children and upon intensive care unit (ICU) admission in 700 critically ill children of a randomized study on glycemic control. RESULTS: Levels of MASP-1, MASP-2, MASP-3, and MAp-44 were lower and the levels of M-ficolin were higher in ICU patients on admission than those in matched healthy controls. Only a low on-admission MASP-3 level was independently associated with risk of new ICU infections and prolonged ICU stay, after correcting for other risk factors. On-admission MASP-3 varied with age, illness severity, and genetic variation. CONCLUSION: Low on-admission MASP-3 levels in critically ill children were independently associated with subsequent acquisition of infection and prolonged ICU stay. The biological explanation needs further investigation.
BACKGROUND: Critically ill children are susceptible to nosocomial infections, which contribute to adverse outcomes. Deficiencies in the innate immunity lectin pathway of complement activation are implicated in a child's vulnerability to infections in conditions such as cancer, but the role during critical illness remains unclear. We hypothesized that low on-admission levels of the pathway proteins are, in part, genetically determined and associated with susceptibility to infectious complications and adverse outcomes. METHODS: We studied protein levels of mannose-binding lectin (MBL), H-ficolin and M-ficolin, three MBL-associated-serine proteases (MASPs) and MBL-associated protein (MAp44), and relation with functional genetic polymorphisms, in 130 healthy children and upon intensive care unit (ICU) admission in 700 critically ill children of a randomized study on glycemic control. RESULTS: Levels of MASP-1, MASP-2, MASP-3, and MAp-44 were lower and the levels of M-ficolin were higher in ICU patients on admission than those in matched healthy controls. Only a low on-admission MASP-3 level was independently associated with risk of new ICU infections and prolonged ICU stay, after correcting for other risk factors. On-admission MASP-3 varied with age, illness severity, and genetic variation. CONCLUSION: Low on-admission MASP-3 levels in critically ill children were independently associated with subsequent acquisition of infection and prolonged ICU stay. The biological explanation needs further investigation.
Authors: S S Krogh; C B Holt; R Steffensen; K L Funck; P Høyem; E Laugesen; P L Poulsen; S Thiel; T K Hansen Journal: Clin Exp Immunol Date: 2017-04-20 Impact factor: 4.330
Authors: Erik C Madsen; Emily R Levy; Kate Madden; Anna A Agan; Ryan M Sullivan; Dionne A Graham; Adrienne G Randolph Journal: Pediatr Crit Care Med Date: 2017-02 Impact factor: 3.624
Authors: Emily R Levy; Wai-Ki Yip; Michael Super; Jill M Ferdinands; Anushay J Mistry; Margaret M Newhams; Yu Zhang; Helen C Su; Gwenn E McLaughlin; Anil Sapru; Laura L Loftis; Scott L Weiss; Mark W Hall; Natalie Cvijanovich; Adam Schwarz; Keiko M Tarquinio; Peter M Mourani; Adrienne G Randolph Journal: Front Immunol Date: 2019-05-08 Impact factor: 7.561
Authors: Marcia H Beltrame; Angelica B W Boldt; Sandra J Catarino; Hellen C Mendes; Stefanie E Boschmann; Isabela Goeldner; Iara Messias-Reason Journal: Mol Immunol Date: 2015-04-08 Impact factor: 4.407