Differential role of the lectin pathway of complement activation in susceptibility to neonatal sepsis

Luregn J Schlapbach; Maika Mattmann; Steffen Thiel; Colette Boillat; Margrith Otth; Mathias Nelle; Bendicht Wagner; Jens C Jensenius; Christoph Aebi

doi:10.1086/653531

Differential role of the lectin pathway of complement activation in susceptibility to neonatal sepsis

Luregn J Schlapbach, Maika Mattmann, Steffen Thiel, Colette Boillat, Margrith Otth, Mathias Nelle, Bendicht Wagner, Jens C Jensenius, Christoph Aebi

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

Abstract

BACKGROUND. The incidence of bacterial sepsis during the neonatal period is high. Mannan-binding lectin (MBL), L-ficolin, and H-ficolin recognize microorganisms and activate the complement system via MBL-associated serine proteases (MASPs). This study investigated whether cord blood concentrations of the lectin pathway proteins are associated with neonatal sepsis. METHODS. This was a case-control study including 47 infants with culture-proven sepsis during the first month of life and 94 matched controls. MBL, L-ficolin, H-ficolin, MASP-2, and MASP-3 levels were measured in cord blood with use of enzyme-linked immunosorbent assay and time-resolved immunofluorometric assay. Multivariate logistic regression was performed. RESULTS. Infants with gram-positive sepsis had significantly lower H-ficolin cord blood concentrations than controls (multivariate odds ratio [OR], 4.00; 95% confidence interval [CI], 1.51-10.56; P = .005), whereas infants with gram-negative sepsis had lower MBL cord blood concentrations (OR, 2.99; 95% CI, 0.86-10.33; P = .084). When excluding patients with postoperative sepsis, multivariate analysis confirmed that low H-ficolin was associated with a significantly higher risk of gram-positive sepsis (OR, 3.71; 95% CI, 1.26-10.92; P = .017) and late-onset sepsis (OR, 3.14; 95% CI, 1.07-9.21; P = .037). In contrast, low MBL was associated with a significantly higher risk of gram-negative sepsis (OR, 4.39; 95% CI, 1.10-17.45; P = .036) and early-onset sepsis (OR, 3.87; 95% CI, 1.05-14.29; P = .042). The concentrations of all the lectin pathway proteins increased with gestational age (P <.01). CONCLUSIONS. These preliminary results indicate that low MBL concentrations are a susceptibility factor for gram-negative sepsis, and low H-ficolin concentrations indicate susceptibility to gram-positive sepsis. The decreased expression of lectin pathway proteins in neonates must be considered to be an additional form of neonatal immunodeficiency.

Originalsprog	Engelsk
Tidsskrift	Clinical Infectious Diseases
Vol/bind	51
Nummer	2
Sider (fra-til)	153-62
Antal sider	10
ISSN	1058-4838
DOI	https://doi.org/10.1086/653531
Status	Udgivet - 15 jul. 2010

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10.1086/653531

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@article{b833729376a443e6b11c626fc9287d10,

title = "Differential role of the lectin pathway of complement activation in susceptibility to neonatal sepsis",

abstract = "BACKGROUND. The incidence of bacterial sepsis during the neonatal period is high. Mannan-binding lectin (MBL), L-ficolin, and H-ficolin recognize microorganisms and activate the complement system via MBL-associated serine proteases (MASPs). This study investigated whether cord blood concentrations of the lectin pathway proteins are associated with neonatal sepsis. METHODS. This was a case-control study including 47 infants with culture-proven sepsis during the first month of life and 94 matched controls. MBL, L-ficolin, H-ficolin, MASP-2, and MASP-3 levels were measured in cord blood with use of enzyme-linked immunosorbent assay and time-resolved immunofluorometric assay. Multivariate logistic regression was performed. RESULTS. Infants with gram-positive sepsis had significantly lower H-ficolin cord blood concentrations than controls (multivariate odds ratio [OR], 4.00; 95% confidence interval [CI], 1.51-10.56; P = .005), whereas infants with gram-negative sepsis had lower MBL cord blood concentrations (OR, 2.99; 95% CI, 0.86-10.33; P = .084). When excluding patients with postoperative sepsis, multivariate analysis confirmed that low H-ficolin was associated with a significantly higher risk of gram-positive sepsis (OR, 3.71; 95% CI, 1.26-10.92; P = .017) and late-onset sepsis (OR, 3.14; 95% CI, 1.07-9.21; P = .037). In contrast, low MBL was associated with a significantly higher risk of gram-negative sepsis (OR, 4.39; 95% CI, 1.10-17.45; P = .036) and early-onset sepsis (OR, 3.87; 95% CI, 1.05-14.29; P = .042). The concentrations of all the lectin pathway proteins increased with gestational age (P <.01). CONCLUSIONS. These preliminary results indicate that low MBL concentrations are a susceptibility factor for gram-negative sepsis, and low H-ficolin concentrations indicate susceptibility to gram-positive sepsis. The decreased expression of lectin pathway proteins in neonates must be considered to be an additional form of neonatal immunodeficiency.",

keywords = "Bacteremia, Case-Control Studies, Complement Pathway, Mannose-Binding Lectin, Complement System Proteins, Enzyme-Linked Immunosorbent Assay, Female, Fluoroimmunoassay, Gram-Negative Bacterial Infections, Gram-Positive Bacterial Infections, Humans, Infant, Newborn, Male, Sepsis",

author = "Schlapbach, {Luregn J} and Maika Mattmann and Steffen Thiel and Colette Boillat and Margrith Otth and Mathias Nelle and Bendicht Wagner and Jensenius, {Jens C} and Christoph Aebi",

year = "2010",

month = jul,

day = "15",

doi = "10.1086/653531",

language = "English",

volume = "51",

pages = "153--62",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "2",

}

Differential role of the lectin pathway of complement activation in susceptibility to neonatal sepsis. / Schlapbach, Luregn J; Mattmann, Maika; Thiel, Steffen et al.
I: Clinical Infectious Diseases, Bind 51, Nr. 2, 15.07.2010, s. 153-62.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Differential role of the lectin pathway of complement activation in susceptibility to neonatal sepsis

AU - Schlapbach, Luregn J

AU - Mattmann, Maika

AU - Thiel, Steffen

AU - Boillat, Colette

AU - Otth, Margrith

AU - Nelle, Mathias

AU - Wagner, Bendicht

AU - Jensenius, Jens C

AU - Aebi, Christoph

PY - 2010/7/15

Y1 - 2010/7/15

N2 - BACKGROUND. The incidence of bacterial sepsis during the neonatal period is high. Mannan-binding lectin (MBL), L-ficolin, and H-ficolin recognize microorganisms and activate the complement system via MBL-associated serine proteases (MASPs). This study investigated whether cord blood concentrations of the lectin pathway proteins are associated with neonatal sepsis. METHODS. This was a case-control study including 47 infants with culture-proven sepsis during the first month of life and 94 matched controls. MBL, L-ficolin, H-ficolin, MASP-2, and MASP-3 levels were measured in cord blood with use of enzyme-linked immunosorbent assay and time-resolved immunofluorometric assay. Multivariate logistic regression was performed. RESULTS. Infants with gram-positive sepsis had significantly lower H-ficolin cord blood concentrations than controls (multivariate odds ratio [OR], 4.00; 95% confidence interval [CI], 1.51-10.56; P = .005), whereas infants with gram-negative sepsis had lower MBL cord blood concentrations (OR, 2.99; 95% CI, 0.86-10.33; P = .084). When excluding patients with postoperative sepsis, multivariate analysis confirmed that low H-ficolin was associated with a significantly higher risk of gram-positive sepsis (OR, 3.71; 95% CI, 1.26-10.92; P = .017) and late-onset sepsis (OR, 3.14; 95% CI, 1.07-9.21; P = .037). In contrast, low MBL was associated with a significantly higher risk of gram-negative sepsis (OR, 4.39; 95% CI, 1.10-17.45; P = .036) and early-onset sepsis (OR, 3.87; 95% CI, 1.05-14.29; P = .042). The concentrations of all the lectin pathway proteins increased with gestational age (P <.01). CONCLUSIONS. These preliminary results indicate that low MBL concentrations are a susceptibility factor for gram-negative sepsis, and low H-ficolin concentrations indicate susceptibility to gram-positive sepsis. The decreased expression of lectin pathway proteins in neonates must be considered to be an additional form of neonatal immunodeficiency.

AB - BACKGROUND. The incidence of bacterial sepsis during the neonatal period is high. Mannan-binding lectin (MBL), L-ficolin, and H-ficolin recognize microorganisms and activate the complement system via MBL-associated serine proteases (MASPs). This study investigated whether cord blood concentrations of the lectin pathway proteins are associated with neonatal sepsis. METHODS. This was a case-control study including 47 infants with culture-proven sepsis during the first month of life and 94 matched controls. MBL, L-ficolin, H-ficolin, MASP-2, and MASP-3 levels were measured in cord blood with use of enzyme-linked immunosorbent assay and time-resolved immunofluorometric assay. Multivariate logistic regression was performed. RESULTS. Infants with gram-positive sepsis had significantly lower H-ficolin cord blood concentrations than controls (multivariate odds ratio [OR], 4.00; 95% confidence interval [CI], 1.51-10.56; P = .005), whereas infants with gram-negative sepsis had lower MBL cord blood concentrations (OR, 2.99; 95% CI, 0.86-10.33; P = .084). When excluding patients with postoperative sepsis, multivariate analysis confirmed that low H-ficolin was associated with a significantly higher risk of gram-positive sepsis (OR, 3.71; 95% CI, 1.26-10.92; P = .017) and late-onset sepsis (OR, 3.14; 95% CI, 1.07-9.21; P = .037). In contrast, low MBL was associated with a significantly higher risk of gram-negative sepsis (OR, 4.39; 95% CI, 1.10-17.45; P = .036) and early-onset sepsis (OR, 3.87; 95% CI, 1.05-14.29; P = .042). The concentrations of all the lectin pathway proteins increased with gestational age (P <.01). CONCLUSIONS. These preliminary results indicate that low MBL concentrations are a susceptibility factor for gram-negative sepsis, and low H-ficolin concentrations indicate susceptibility to gram-positive sepsis. The decreased expression of lectin pathway proteins in neonates must be considered to be an additional form of neonatal immunodeficiency.

KW - Bacteremia

KW - Case-Control Studies

KW - Complement Pathway, Mannose-Binding Lectin

KW - Complement System Proteins

KW - Enzyme-Linked Immunosorbent Assay

KW - Female

KW - Fluoroimmunoassay

KW - Gram-Negative Bacterial Infections

KW - Gram-Positive Bacterial Infections

KW - Humans

KW - Infant, Newborn

KW - Male

KW - Sepsis

U2 - 10.1086/653531

DO - 10.1086/653531

M3 - Journal article

C2 - 20528471

SN - 1058-4838

VL - 51

SP - 153

EP - 162

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 2

ER -

Differential role of the lectin pathway of complement activation in susceptibility to neonatal sepsis

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