title: Components of the lectin pathway of complement activation in paediatric patients of intensive care units.
abstract: Infections are a major cause of childhood mortality. We investigated components of the lectin pathway of complement activation in the context of sepsis at both genetic and protein levels in neonates, infants and older children. Major components of the lectin pathway and two genes for Toll-like receptors were studied in 87 neonates with confirmed sepsis and compared with 40 babies with infections who did not develop sepsis (disease controls) and 273 infection-free neonatal controls. A second cohort comprised 47 older children with sepsis and 87 controls. Low MBL-conferring genotypes (LXA/O+O/O) were more frequent in sepsis patients than in healthy controls but no significant differences in the frequency of SNPs of other lectin pathway genes (FCN1, FCN2, FCN3, MASP1/3, MASP2) or TLR receptor genes (TLR2, TLR4) were found. One case of primary MASP-2 deficiency was found among healthy pre-terms and one neonate suffering from SIRS was heterozygous for the rare FCN1 gene mutation, +6658 G>A. Generally, sepsis was associated with low serum MBL and low ficolin-2 concentrations on admission. Among neonates, ficolin-1 and MASP-2 levels were elevated in sepsis relative to healthy, but not disease, controls. Unlike neonates, ficolin-3 and MASP-2 levels were lower in older patients than in healthy controls while no difference was found for ficolin-1. With the possible exception of MBL, inherited lectin pathway insufficiencies do not seem to predispose to sepsis, rather changes in protein concentrations reflect alterations in disease course.
authors: Laboratory of Immunobiology of Infections, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland.
authors: Anna S
authors: AS
authors: Świerzko
authors: Laboratory of Immunobiology of Infections, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland.
authors: Agnieszka
authors: A
authors: Szala-Poździej
authors: Scottish National Blood Transfusion Service, National Science Laboratory, Ellen's Glen Road, Edinburgh, EH17 7QT Scotland, UK.
authors: David C
authors: DC
authors: Kilpatrick
authors: Department of Anesthesiology and Intensive Therapy, Polish Mother's Memorial Hospital Research Institute, Rzgowska 281/289, 93-338 Lodz, Poland.
authors: Michał
authors: M
authors: Sobociński
authors: Department of Newborns Infectious Diseases, Poznan University of Medical Sciences, Polna 33, 60-533 Poznan, Poland.
authors: Karolina
authors: K
authors: Chojnacka
authors: Laboratory of Immunobiology of Infections, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland.
authors: Anna
authors: A
authors: Sokołowska
authors: Laboratory of Immunobiology of Infections, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland; Institute of Microbiology, Biotechnology and Immunology, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland.
authors: Mateusz
authors: M
authors: Michalski
authors: Laboratory of Immunobiology of Infections, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland.
authors: Karolina
authors: K
authors: Mazerant
authors: Department of Biomedicine, Aarhus University, Vennellyst Boulevard 4, Aarhus DK-8000, Denmark.
authors: Jens C
authors: JC
authors: Jensenius
authors: Department of Applied Biochemistry, Tokai University, 4-1-1 Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan.
authors: Misao
authors: M
authors: Matsushita
authors: Department of Anesthesiology and Intensive Therapy, Polish Mother's Memorial Hospital Research Institute, Rzgowska 281/289, 93-338 Lodz, Poland.
authors: Wojciech R
authors: WR
authors: Krajewski
authors: Department of Newborns Infectious Diseases, Poznan University of Medical Sciences, Polna 33, 60-533 Poznan, Poland.
authors: Jerzy
authors: J
authors: Szczapa
authors: Department of Nutrition in Digestive Tract Diseases, Medical University of Lodz, Rzgowska 281/289, 93-338 Lodz, Poland.
authors: Leokadia
authors: L
authors: Bąk-Romaniszyn
authors: Department of Paediatrics, Immunology and Nephrology, Polish Mother's Memorial Hospital Research Institute, Rzgowska 281/289, 93-338 Lodz, Poland.
authors: Krzysztof
authors: K
authors: Zeman
authors: Laboratory of Immunobiology of Infections, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland. Electronic address: mcedzynski@cbm.pan.pl.
authors: Maciej
authors: M
authors: Cedzyński
mesh_terms: D000483:Alleles; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000401:mortality; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003167:Complement Activation; D037582:Complement Pathway, Mannose-Binding Lectin / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007223:Infant; D007362:Intensive Care Units; D037102:Lectins / Q000235:genetics / Q000378:metabolism; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics / Q000276:immunology; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D018805:Sepsis / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000401:mortality; D000097604:Ficolins
chemical_list: D037102:Lectins; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases; D000097604:Ficolins
keywords: ); Complement; Ficolin; Innate immunity; MASP; Mannose-binding lectin (mannan-binding lectin, MBL; Sepsis